Les travaux

Sommité de la médecine des soins intensifs et de la méthodologie de recherche en santé, la Dre Cook a contribué pendant 30 ans à la conception et à la conduite d’études cliniques qui ont changé la pratique et apporté des améliorations majeures dans les soins prodigués aux patients les plus gravement malades en milieu hospitalier. Ses intérêts pour la recherche multi-méthodes et multidisciplinaire englobent les soins de survie avancés, la prévention des complications acquises en USI, l’éthique de la recherche et les soins de fin de vie.

Elle a relevé des défis éthiques complexes alors que des patients assistés par la technologie passent de la vie à la mort, grâce au projet 3 Wishes adopté à l’échelle internationale. Ce modèle interprofessionnel unique de soins de fin de vie encourage les cliniciens d’horizons différents à améliorer le passage vers la mort de patients hospitalisés en honorant leur vie, en facilitant le deuil pour la famille et en favorisant l’humanisme dans la pratique. Le projet 3 Wishes aide à identifier et à répondre aux besoins des patients mourant à l’hôpital en suscitant et en exauçant leurs dernières volontés importantes, ce qui s’est avéré particulièrement utile pendant la pandémie alors que les visites familiales étaient restreintes pour les patients hospitalisés, y compris ceux rendus en fin de vie.

La Dre Cook a été membres fondatrice de la première collaboration fructueuse en recherche sur les soins intensifs au monde – le Groupe canadien de recherche en soins intensifs – qui a prospéré sous sa direction, en tant que présidente et championne de la recherche centrée sur le patient initiée par des chercheurs.

L’impact

Les recherches de la Dre Cook ont aidé à atténuer les énormes coûts humains et économiques des maladies graves pour les patients, les familles, les systèmes de santé et la société. La Dre Cook a conçu et réalisé plusieurs études nationales et internationales marquantes sur la meilleure façon de prévenir les complications courantes et souvent mortelles de maladies graves telles que les caillots sanguins, les infections pulmonaires et les saignements gastro-intestinaux, fournissant des preuves essentielles pour les examens et les lignes directrices appliqués au chevet du patient partout dans le monde. Elle a contribué avec passion à améliorer le domaine des soins intensifs, réduisant la morbidité et sauvant des vies dans les USI, ce qui a eu un impact sur la pratique des soins intensifs à l’échelle mondiale. Elle a également défendu des modèles de soins de fin de vie compatissants qui ont un impact sur les familles, les patients et les soignants.

Au cours de sa carrière, la Dre Cook s’est vu décerner des dizaines de distinctions nationales et internationales reconnaissant ses contributions exceptionnelles à la recherche sur les soins intensifs. Ses travaux de recherche portent sur la création d’avantages sanitaires, sociaux et économiques mesurables pour les patients qui nécessitent des soins de vie avancés. Ses recherches pionnières ont transformé la médecine des soins intensifs et ont eu globalement des répercussions durables sur les patients, la pratique et les politiques.

Les travaux

La carrière du Dr Zulfiqar Bhutta s’est concentrée sur l’amélioration de la santé et de la nutrition des enfants et des mères parmi les populations marginalisées et rurales, en utilisant des stratégies et des interventions fondées sur des données probantes pour améliorer les résultats au cours des « mille premiers jours » de la vie (grossesse, accouchement et les deux premières années de vie). En développant une collaboration unique entre des centres au Pakistan, au Royaume-Uni et au Canada, le Dr Bhutta a mobilisé des essais d’efficacité randomisés en grappes (cRCT) pour recueillir des données destinées à concevoir et à améliorer des programmes d’intervention en soins maternels et néonatals communautaires, en nutrition et en développement de la petite enfance.

L’impact

Les travaux du Dr Bhutta ont servi de fondement à plusieurs directives internationales, y compris la modification de la politique de l’OMS sur le traitement de la diarrhée persistante et de la malnutrition, ainsi que l’implantation d’agentes de santé féminines (ASF) en tant que membres fondatrices des interventions communautaires au Pakistan, en Asie du Sud et en Afrique sub-saharienne. En outre, son travail a été à la base des interventions nutritionnelles « Lancet 10 », employées pour éclairer la politique mondiale sur la malnutrition. Au cours des deux dernières décennies, ses travaux consacrés aux interventions fondées sur des données probantes ont contribué à orienter les plans d’action mondiaux visant à améliorer la santé et la survie des nouveau-nés. Son approche rigoureuse de la recherche a également contribué à remettre en question certaines idées reçues, en illustrant à la fois les possibilités et les limites d’interventions vitales comme les agents de santé communautaires.

Le Dr Bhutta a beaucoup travaillé dans des milieux à faibles ressources, en ayant recours à des interventions durables qui sont disponibles et abordables pour les populations défavorisées. Grâce à une recherche et une analyse systématiques, il a jeté les bases de la compréhension actuelle de la santé maternelle et infantile dans les régions rurales, éloignées ou touchées par des conflits, et il a amélioré la survie et la situation des femmes et des enfants les plus vulnérables dans le monde.

Les travaux

Les Drs Karikó et Weissman ont découvert comment concevoir l’ARNm – une molécule qui transporte des instructions pour fabriquer des protéines – afin qu’elle puisse servir à produire la protéine souhaitée après son introduction dans des cellules de mammifères. Ils ont surmonté l’activation inflammatoire et la dégradation rapide de l’ARNm en modifiant l’ARN afin qu’il puisse résister à une désintégration rapide et éviter l’activation des capteurs d’ARN. Malgré le scepticisme de certains, les Dr Karikó et Weissman ont vu le potentiel des thérapies à base d’ARN pour les vaccins et d’autres applications et les données ont continué à les faire avancer. Cependant, un défi majeur subsistait : comment introduire l’ARNm dans le corps de manière à ce qu’il soit protégé de la dégradation et puisse entrer dans les cellules afin d’y produire des protéines.

Le Dr Cullis travaille avec de tels systèmes d’encapsidation depuis 50 ans. Il est un pionnier de la chimie des lipides et de la formation de nanoparticules lipidiques (NPL). À partir de ses travaux fondamentaux, de nombreuses applications cliniques des NPL ont été développées, telles que l’administration de médicaments anticancéreux dans les tissus cancéreux tout en limitant leur toxicité dans les tissus normaux. Dans le cas de l’ARNm, les NPL sont conçues pour former une bulle protectrice autour de l’ARNm et permettre sa livraison à l’intérieur des cellules cibles. La technologie des NPL est essentielle à l’efficacité des vaccins à ARNm.

Suite à l’apparition du virus SARS-CoV2, diverses équipes un peu partout dans le monde ont commencé à travailler sur des vaccins potentiels en utilisant les connaissances acquises au fil des décennies sur l’ARNm et les nanoparticules lipidiques. Le principe des vaccins Pfizer/BioNTech et Moderna était d’introduire dans le corps des molécules d’ARNm modifiées via des NPL pour inciter brièvement des cellules humaines à produire la protéine de spicule du coronavirus. Le système immunitaire activé par la NPL reconnaîtrait la protéine virale codée et développerait des anticorps et une mémoire immunitaire afin que le système immunitaire puisse attaquer le coronavirus à son entrée dans le corps.

L’impact

Les travaux des Drs Karikó, Weissman et Cullis ont facilité la disponibilité rapide de vaccins à ARNm hautement efficaces et sûrs contre la COVID-19, lesquels sont devenus un outil important dans le contrôle de la pandémie de COVID-19. Il est important de noter que leurs découvertes cruciales ont également le potentiel de révolutionner l’administration future de vaccins, de thérapies et de thérapies géniques efficaces et sûrs. Le succès des vaccins à ARNm contre la COVID-19 suggère des voies à suivre pour développer des vaccins similaires contre des menaces virales comme la grippe ou le VIH. Des essais cliniques sont déjà en cours pour tester des vaccins à ARNm en vue de prévenir les maladies causées par le virus Zika, le chikungunya et les infections rabiques.

Les vaccins à ARNm contre la COVID-19 élaborés par Pfizer/BioNTech et Moderna s’appuient sur plus de 30 années de recherche scientifique établie et ils soulignent l’importance de la recherche fondamentale et appliquée, ainsi que de la collaboration internationale.

Les travaux

Les Drs Karikó et Weissman ont découvert comment concevoir l’ARNm – une molécule qui transporte des instructions pour fabriquer des protéines – afin qu’elle puisse servir à produire la protéine souhaitée après son introduction dans des cellules de mammifères. Ils ont surmonté l’activation inflammatoire et la dégradation rapide de l’ARNm en modifiant l’ARN afin qu’il puisse résister à une désintégration rapide et éviter l’activation des capteurs d’ARN. Malgré le scepticisme de certains, les Dr Karikó et Weissman ont vu le potentiel des thérapies à base d’ARN pour les vaccins et d’autres applications et les données ont continué à les faire avancer. Cependant, un défi majeur subsistait : comment introduire l’ARNm dans le corps de manière à ce qu’il soit protégé de la dégradation et puisse entrer dans les cellules afin d’y produire des protéines.

Le Dr Cullis travaille avec de tels systèmes d’encapsidation depuis 50 ans. Il est un pionnier de la chimie des lipides et de la formation de nanoparticules lipidiques (NPL). À partir de ses travaux fondamentaux, de nombreuses applications cliniques des NPL ont été développées, telles que l’administration de médicaments anticancéreux dans les tissus cancéreux tout en limitant leur toxicité dans les tissus normaux. Dans le cas de l’ARNm, les NPL sont conçues pour former une bulle protectrice autour de l’ARNm et permettre sa livraison à l’intérieur des cellules cibles. La technologie des NPL est essentielle à l’efficacité des vaccins à ARNm.

Suite à l’apparition du virus SARS-CoV2, diverses équipes un peu partout dans le monde ont commencé à travailler sur des vaccins potentiels en utilisant les connaissances acquises au fil des décennies sur l’ARNm et les nanoparticules lipidiques. Le principe des vaccins Pfizer/BioNTech et Moderna était d’introduire dans le corps des molécules d’ARNm modifiées via des NPL pour inciter brièvement des cellules humaines à produire la protéine de spicule du coronavirus. Le système immunitaire activé par la NPL reconnaîtrait la protéine virale codée et développerait des anticorps et une mémoire immunitaire afin que le système immunitaire puisse attaquer le coronavirus à son entrée dans le corps.

L’impact

Les travaux des Drs Karikó, Weissman et Cullis ont facilité la disponibilité rapide de vaccins à ARNm hautement efficaces et sûrs contre la COVID-19, lesquels sont devenus un outil important dans le contrôle de la pandémie de COVID-19. Il est important de noter que leurs découvertes cruciales ont également le potentiel de révolutionner l’administration future de vaccins, de thérapies et de thérapies géniques efficaces et sûrs. Le succès des vaccins à ARNm contre la COVID-19 suggère des voies à suivre pour développer des vaccins similaires contre des menaces virales comme la grippe ou le VIH. Des essais cliniques sont déjà en cours pour tester des vaccins à ARNm en vue de prévenir les maladies causées par le virus Zika, le chikungunya et les infections rabiques.

Les vaccins à ARNm contre la COVID-19 élaborés par Pfizer/BioNTech et Moderna s’appuient sur plus de 30 années de recherche scientifique établie et ils soulignent l’importance de la recherche fondamentale et appliquée, ainsi que de la collaboration internationale.

Les travaux

Les Drs Karikó et Weissman ont découvert comment concevoir l’ARNm – une molécule qui transporte des instructions pour fabriquer des protéines – afin qu’elle puisse servir à produire la protéine souhaitée après son introduction dans des cellules de mammifères. Ils ont surmonté l’activation inflammatoire et la dégradation rapide de l’ARNm en modifiant l’ARN afin qu’il puisse résister à une désintégration rapide et éviter l’activation des capteurs d’ARN. Malgré le scepticisme de certains, les Dr Karikó et Weissman ont vu le potentiel des thérapies à base d’ARN pour les vaccins et d’autres applications et les données ont continué à les faire avancer. Cependant, un défi majeur subsistait : comment introduire l’ARNm dans le corps de manière à ce qu’il soit protégé de la dégradation et puisse entrer dans les cellules afin d’y produire des protéines.

Le Dr Cullis travaille avec de tels systèmes d’encapsidation depuis 50 ans. Il est un pionnier de la chimie des lipides et de la formation de nanoparticules lipidiques (NPL). À partir de ses travaux fondamentaux, de nombreuses applications cliniques des NPL ont été développées, telles que l’administration de médicaments anticancéreux dans les tissus cancéreux tout en limitant leur toxicité dans les tissus normaux. Dans le cas de l’ARNm, les NPL sont conçues pour former une bulle protectrice autour de l’ARNm et permettre sa livraison à l’intérieur des cellules cibles. La technologie des NPL est essentielle à l’efficacité des vaccins à ARNm.

Suite à l’apparition du virus SARS-CoV2, diverses équipes un peu partout dans le monde ont commencé à travailler sur des vaccins potentiels en utilisant les connaissances acquises au fil des décennies sur l’ARNm et les nanoparticules lipidiques. Le principe des vaccins Pfizer/BioNTech et Moderna était d’introduire dans le corps des molécules d’ARNm modifiées via des NPL pour inciter brièvement des cellules humaines à produire la protéine de spicule du coronavirus. Le système immunitaire activé par la NPL reconnaîtrait la protéine virale codée et développerait des anticorps et une mémoire immunitaire afin que le système immunitaire puisse attaquer le coronavirus à son entrée dans le corps.

L’impact

Les travaux des Drs Karikó, Weissman et Cullis ont facilité la disponibilité rapide de vaccins à ARNm hautement efficaces et sûrs contre la COVID-19, lesquels sont devenus un outil important dans le contrôle de la pandémie de COVID-19. Il est important de noter que leurs découvertes cruciales ont également le potentiel de révolutionner l’administration future de vaccins, de thérapies et de thérapies géniques efficaces et sûrs. Le succès des vaccins à ARNm contre la COVID-19 suggère des voies à suivre pour développer des vaccins similaires contre des menaces virales comme la grippe ou le VIH. Des essais cliniques sont déjà en cours pour tester des vaccins à ARNm en vue de prévenir les maladies causées par le virus Zika, le chikungunya et les infections rabiques.

Les vaccins à ARNm contre la COVID-19 élaborés par Pfizer/BioNTech et Moderna s’appuient sur plus de 30 années de recherche scientifique établie et ils soulignent l’importance de la recherche fondamentale et appliquée, ainsi que de la collaboration internationale.

Les travaux

Les travaux pionniers du Dr Stuart Orkin sur les troubles génétiques de l’hémoglobine s’étendent sur quatre décennies et ont dévoilé les mystères moléculaires derrière la façon dont les cellules sanguines se développent et la façon dont les troubles sanguins surviennent. Ses études les plus récentes ont mené à la découverte du mécanisme moléculaire responsable du passage de l’expression du gène de l’hémoglobine du stade fœtal (HbF) au stade adulte (HbA), qui se produit au cours du développement humain. À partir d’indices génétiques provenant d’études sur la population humaine, Orkin et ses collègues ont établi que la protéine BCL11A agit comme un silencieux critique de l’expression de l’HbF chez les adultes. Reconnaissant que la réactivation de l’expression de l’HbF pourrait réduire la gravité de la drépanocytose et de la bêta-thalassémie – des troubles génétiques affectant la production d’HbA – il a proposé une régulation à la baisse de BCL11A comme approche thérapeutique. La réduction de la quantité de BCL11A réactiverait l’expression de l’HbF et remplacerait efficacement l’HbA mutante ou déficiente dans ces troubles. Son groupe a d’abord démontré que la régulation à la baisse de l’expression de BCL11A corrige la drépanocytose chez des souris modifiées, une démonstration de principe importante pour l’application thérapeutique. Lui et ses collègues ont identifié un site discret dans un élément régulateur au sein du gène BCL11A lui-même qui, s’il était supprimé par édition génique CRISPR dans les cellules souches sanguines, n’altérerait l’expression de BCL11A que dans les globules rouges en développement et réactiverait en toute sécurité l’expression de l’HbF. Ces travaux ont jeté les bases d’essais cliniques en cours très prometteurs chez des patients atteints de drépanocytose et de bêta-thalassémie, des maladies qui affectent >5 millions d’individus dans le monde. La réactivation de l’HbF chez les patients participant à ces essais de thérapie génique a donné des résultats transformateurs : absence de crises de drépanocytose et d’anémie dans la drépanocytose et indépendance transfusionnelle dans la bêta-thalassémie.

L’impact

Une grande partie de ce que l’on sait sur le contrôle de l’expression génique au cours du développement des cellules sanguines peut être attribuée directement aux études pionnières d’Orkin. Ses découvertes ont ouvert la voie à des approches cliniques qui révolutionneront le traitement de troubles de l’hémoglobine – la drépanocytose et la bêta-thalassémie – qui touchent plus de cinq millions de personnes à travers le monde. Les essais cliniques en cours établissent le potentiel thérapeutique de la réactivation de l’HbF. Les résultats de ces essais auront un impact significatif sur les patients souffrant de troubles de l’hémoglobine partout dans le monde et favoriseront l’élaboration future de thérapies moins chères et plus facilement accessibles pour une application universelle.

Les travaux
Le Dr John Dick a fait la première découverte de cellules souches leucémiques (CSL) chez un patient atteint de leucémie myéloïde aiguë (LMA). Cette découverte a établi que les cellules cancéreuses individuelles chez un patient ne sont pas égales, mais sont plutôt organisées en une hiérarchie cellulaire où seules de rares cellules leucémiques sont capables d’auto-renouvellement, la propriété clé des cellules souches. Cette découverte a nécessité deux composantes expérimentales élaborées par le Dr Dick : un test de xénogreffe pour détecter les CSL en fonction de leur capacité à générer une leucémie humaine lors de la transplantation chez des souris immunodéficientes, et une méthode pour purifier les cellules leucémiques en populations CSL et non CSL. En combinant des tests CSL fonctionnels avec une analyse génétique, le Dr Dick a pu suivre les voies évolutives complexes du développement de la leucémie humaine, de cellules souches sanguines normales à des cellules souches pré-leucémiques, lesquelles engendrent éventuellement des CSL et la LMA jusqu’à une décennie plus tard. Ces travaux ont également montré que les CSL qui peuvent provoquer une rechute ultérieure ont déjà évolué avant le diagnostic et peuvent survivre aux procédures thérapeutiques normales. Ainsi, des CSL étaient directement liées à l’échec du traitement et à la rechute chez les patients atteints de leucémie. Les propriétés des CSL telles que reflétées dans leur expression génique sont prédictives de la réponse thérapeutique et de la survie globale. Le Dr Dick a développé un « score souche » visant 17 gènes qui peut être utilisé en clinique afin de déterminer le risque de piètres résultats pour le patient et aider à guider le choix thérapeutique.

L’impact
La découverte des CSL par le Dr Dick a changé la compréhension de la biologie sous-jacente du cancer et a stimulé l’exploration des cellules souches cancéreuses (CSC) dans d’autres cancers humains, y compris ceux affectant le sein, le cerveau, le côlon, le pancréas, la peau et le foie. Ses travaux ont souligné l’importance d’étudier les propriétés des cellules individuelles du clone néoplasique, plutôt que les cellules cancéreuses dans leur ensemble, et l’attention particulière qui doit être accordée aux CSC, les seules cellules capables de propager le cancer à long terme. L’accent mis sur les CSC dévoile un certain nombre de propriétés à l’origine de leur survie à la thérapie, notamment la dormance, la signalisation du stress, ainsi que les programmes souches qui facilitent la récurrence de la maladie. Les travaux du Dr Dick ont fait ressortir la nécessité de s’assurer que la thérapie administrée éradique les CSC, et le besoin de développer de nouvelles thérapies ciblant les vulnérabilités des CSC. La découverte de la présence de cellules souches pré-leucémiques plusieurs années avant l’apparition de la maladie et de la présence de CSL récidivantes au moment du diagnostic offre des fenêtres d’opportunité pour cibler le stade pré-leucémique et celui de la rechute plus tôt, afin de prévenir la maladie et la récidive, respectivement. Les découvertes du Dr Dick offrent une orientation claire pour améliorer les résultats cliniques dans la lutte contre la leucémie grâce au ciblage des CSL et, potentiellement, dans d’autres cancers qui correspondent au modèle des CSC.

The Work:

Dr. John Dick made the first discovery of leukemia stem cells (LSC) in an acute myeloid leukemia (AML) patient. This finding established that individual cancer cells in the patient are not equal, rather they are organized as a cellular hierarchy where only rare leukemia cells possess self- renewal, the hallmark stem cell property. This discovery required two experimental components that Dick developed: a xenograft assay to detect LSC based on their ability to generate human leukemia upon transplantation into immune-deficient mice, and a method to purify leukemia cells into LSC and non-LSC populations. By combining functional LSC assays with genetic analysis, Dick tracked the complex evolutionary pathways of human leukemia development from normal blood stem cells to pre-leukemic stem cells that eventually generate LSC and AML up to a decade later. This work also showed that LSCs that can cause later relapse have already evolved prior to diagnosis, and can survive normal therapy procedures. Thus, LSC were directly linked to therapy failure and relapse in leukemia patients. The properties of LSC as reflected in their gene expression are predictive of therapy response and overall survival. Dick developed a 17-gene ‘stemness score’ that can be used clinically to determine patient risk of poor outcome and help guide therapeutic choice.

The Impact:

Dick’s discovery of LSC changed the understanding of the underlying biology of cancer and stimulated exploration of cancer stem cells (CSCs) in other human cancers, including those affecting the breast, brain, colon, pancreas, skin and liver. His work highlighted the importance of investigating the properties of individual cells of the neoplastic clone, rather than bulk cancer cells and that special attention needs to be on the CSC that are the only cells capable of long term cancer propagation. The focus on CSC is revealing a number of properties that enable their survival in the face of therapy including dormancy, stress signaling as well as stemness programs that enable disease recurrence. Dick’s work points to the need to ensure that CSC are eradicated when therapy is delivered and the need for new therapies that target CSC vulnerabilities. The discovery that pre-leukemic stem cells are present many years prior to disease appearance and that relapse-fated LSC are already present at diagnosis both offer windows of opportunity to target pre-leukemia and relapse earlier to prevent disease and relapse from occurring, respectively. Dick’s findings offer clear direction for improving clinical outcomes in leukemia through LSC targeting and potentially in other cancers that adhere to the CSC model.

The Work:

Dr. Stuart Orkin’s pioneering work in genetic disorders of hemoglobin spans four decades and has unravelled molecular mysteries behind how blood cells develop and how disorders of blood arise. His most recent studies led to the discovery of the molecular mechanism responsible for the switch from fetal (HbF) to adult (HbA) hemoglobin gene expression that occurs during human development. Capitalizing on genetic clues from human population studies, Orkin and colleagues established that the protein BCL11A acts as the critical silencer of HbF expression in adults. Recognizing that turning HbF expression back on could lessen disease severity of sickle cell disease and beta-thalassemia --genetic disorders affecting HbA production – he proposed downregulation of BCL11A as a therapeutic approach. Dialing down the amount of BCL11A would reactivate HbF expression and effectively substitute for mutant or deficient HbA in these disorders. His group first demonstrated that downregulation of BCL11A expression corrects sickle cell disease in engineered mice, an important proof-of-principle for therapeutic translation. He and colleagues identified a discrete site in a regulatory element within the BCL11A gene itself that, if deleted by CRISPR gene editing in blood stem cells, would impair BCL11A expression only within developing red blood cells, and safely reactivate HbF expression. This work laid the groundwork for highly promising, ongoing clinical trials in patients with sickle cell disease and beta-thalassemia, diseases that affect >5 million individuals worldwide. Reactivation of HbF in patients in these genetic therapy trials has yielded transformative results: freedom from sickle crises and anemia in sickle cell disease and transfusion-independence in beta-thalassemia.

The Impact:

Much of what is known about the control of gene expression during blood cell development can be traced directly to Orkin’s pioneering studies. His discoveries have paved the way for clinical approaches that will revolutionize the treatment of hemoglobin disorders – sickle cell disease and beta-thalassemia – that affect more than five million people worldwide. Clinical trials that are currently underway establish the therapeutic potential of HbF reactivation. The outcomes of these trials will have significant impact for patients suffering from hemoglobin disorders around the globe, and will encourage the future development of cheaper and more readily accessible therapies for global application.

The Work:

Drs. Karikó and Weissman discovered how to engineer mRNA – a molecule that carries instructions for making proteins – so that it could be used to produce the desired protein after introduction into mammalian cells. They overcame the inflammatory activation and rapid degradation of mRNA by modifying the RNA so that it could resist quick breakdown and avoid activating RNA sensors. Despite skepticism from others, Drs. Karikó and Weissman saw the potential of RNA therapeutics for vaccines and other applications and the data kept leading them forward. However, one major challenge remained: how to introduce the mRNA into the body in a way that it would be protected from degradation, and could enter into the cells for protein production.

Dr. Cullis had been working with such packaging systems for the past 50 years. Dr. Cullis is a pioneer in lipid chemistry and the formation of lipid nanoparticles (LNP). From his foundational work, many different clinical applications of LNPs have been developed, such as delivering anticancer drugs to cancer tissues while limiting toxicity in normal tissues. In the case of mRNA the LNP are designed to form a protective bubble around the mRNA and enable delivery to the interior of target cells. The LNP technology is critical to the potency of mRNA vaccines.

Following the emergence of the SARS-CoV2 virus, various teams around the world began working on potential vaccines using the knowledge gained about the mRNA and lipid nanoparticle through decades. The idea for both the Pfizer/BioNTech and Moderna vaccines was to introduce modified mRNA molecules into the body via LNPs to briefly instruct human cells to produce the coronavirus’ spike protein. The LNP-activated immune system would recognize the encoded viral protein and develop antibodies and immune memory so that the immune system would attack the coronavirus when entering the body.

The Impact:

The work of Drs. Karikó, Weissman and Cullis enabled the rapid availability of highly effective and safe COVID-19 mRNA vaccines, which has become an important tool for the control of COVID-19 pandemic. Importantly their pivotal discoveries also have the potential to revolutionize the future delivery of effective and safe vaccines, therapeutics and gene therapies. The success of the mRNA vaccines for COVID-19 suggests paths forward for similar vaccines for viral threats like influenza or HIV. Clinical trials are already underway to test mRNA vaccines to prevent diseases, caused by Zika virus, chikungunya and rabies infections.

The COVID-19 mRNA vaccines developed by Pfizer/BioNTech and Moderna are built on over 30 years of established scientific research and highlight the importance of basic and applied research, and international collaboration.

The Work:

Dr. Zulfiqar Bhutta’s career has focused on the improvement of child and maternal health and nutrition among marginalized and rural populations, using evidence based strategies and interventions to improve outcomes in the “first thousand days” of life (pregnancy, childbirth, and the first two years of life). Developing a unique collaboration between centres in Pakistan, United Kingdom and Canada, Bhutta has mobilized cluster randomized effectiveness trials (cRCTs) to gather data used to shape and improve intervention packages for community based maternal and newborn care, nutrition, and early childhood development.

The Impact:

Dr. Bhutta’s work has been the foundation of multiple international guidelines, including changing WHO policy on the treatment of persistent diarrhea and malnutrition along with establishing lady health workers (LHW) as foundational members of community-based interventions in Pakistan, South Asia and sub-Saharan Africa. Further, his work provided the basis for the “Lancet 10” nutritional interventions used to inform global policy on malnutrition. Over the last two decades, his work on evidence-based interventions has helped guide global action plans to improve newborn health and survival. His rigorous approach to investigation has also challenged conventional wisdom, illustrating both the possibilities and limitations of vital interventions like community health workers.

Dr. Bhutta has worked extensively in low resource areas, using sustainable interventions that are available and affordable to disadvantaged populations. Through systematic investigation and analysis, he has established the foundations for current understandings of maternal and child health in rural, remote and conflict affected regions, and improved the survival and outcomes of world’s most vulnerable women and children.

The Work:

Drs. Karikó and Weissman discovered how to engineer mRNA – a molecule that carries instructions for making proteins – so that it could be used to produce the desired protein after introduction into mammalian cells. They overcame the inflammatory activation and rapid degradation of mRNA by modifying the RNA so that it could resist quick breakdown and avoid activating RNA sensors. Despite skepticism from others, Drs. Karikó and Weissman saw the potential of RNA therapeutics for vaccines and other applications and the data kept leading them forward. However, one major challenge remained: how to introduce the mRNA into the body in a way that it would be protected from degradation, and could enter into the cells for protein production.

Dr. Cullis had been working with such packaging systems for the past 50 years. Dr. Cullis is a pioneer in lipid chemistry and the formation of lipid nanoparticles (LNP). From his foundational work, many different clinical applications of LNPs have been developed, such as delivering anticancer drugs to cancer tissues while limiting toxicity in normal tissues. In the case of mRNA the LNP are designed to form a protective bubble around the mRNA and enable delivery to the interior of target cells. The LNP technology is critical to the potency of mRNA vaccines.

Following the emergence of the SARS-CoV2 virus, various teams around the world began working on potential vaccines using the knowledge gained about the mRNA and lipid nanoparticle through decades. The idea for both the Pfizer/BioNTech and Moderna vaccines was to introduce modified mRNA molecules into the body via LNPs to briefly instruct human cells to produce the coronavirus’ spike protein. The LNP-activated immune system would recognize the encoded viral protein and develop antibodies and immune memory so that the immune system would attack the coronavirus when entering the body.

The Impact:

The work of Drs. Karikó, Weissman and Cullis enabled the rapid availability of highly effective and safe COVID-19 mRNA vaccines, which has become an important tool for the control of COVID-19 pandemic. Importantly their pivotal discoveries also have the potential to revolutionize the future delivery of effective and safe vaccines, therapeutics and gene therapies. The success of the mRNA vaccines for COVID-19 suggests paths forward for similar vaccines for viral threats like influenza or HIV. Clinical trials are already underway to test mRNA vaccines to prevent diseases, caused by Zika virus, chikungunya and rabies infections.

The COVID-19 mRNA vaccines developed by Pfizer/BioNTech and Moderna are built on over 30 years of established scientific research and highlight the importance of basic and applied research, and international collaboration.

The Work:

As the foremost authority in critical care medicine and health research methodology, Dr. Cook’s 30-year contributions to the design and the conduct of practice-changing clinical studies have led to major improvements in the care of hospital’s sickest patients. Her multi-method multi-disciplinary research interests include advanced life support, prevention of ICU-acquired complications, research ethics and end-of-life care.

She has addressed complex ethical challenges as patients receiving technology transition from life to death through the internationally-adopted ‘3 Wishes Project’. This unique inter-professional model of end-of-life care encourages clinicians with different backgrounds to improve the dying experience for hospitalized patients by honouring their lives, easing family grief, and fostering humanism in practice. The 3 Wishes Project helps to identify and meet the needs of patients dying in hospital by eliciting and fulfilling final meaningful wishes for them, which has proven particularly helpful during the pandemic as family visits are limited for hospitalized patients, including those at the end-of-life.

Dr. Cook was a founding member of the first successful critical care research collaboration in the world – the Canadian Critical Care Trials Group – which flourished under her leadership as chair and champion of patient-centred investigator-initiated research.

The Impact:

Dr. Cook’s research has helped to alleviate the enormous human and economic costs of critical illness for patients, families, healthcare systems and society. Dr. Cook has designed and conducted several landmark national and international studies on how best to prevent common and often lethal complications of critical illness such as blood clots, lung infections and gastrointestinal bleeding, providing key evidence for reviews and guidelines used at the bedside worldwide. She has passionately improved the field of critical care, reducing morbidity and saving lives in the ICU, impacting critical care practice across the globe. She has also championed compassionate end-of-life care models that impact families, patients and care providers.

Over her career, Dr. Cook has garnered dozens of national and international honours recognizing her outstanding contributions to critical care research. Her research focuses on creating measurable health, social and economic benefits for patients needing advanced life support. Her pioneering research has transformed critical care medicine and has had an enduring global impact on patients, practice, and policy.

The Work:

Drs. Karikó and Weissman discovered how to engineer mRNA – a molecule that carries instructions for making proteins – so that it could be used to produce the desired protein after introduction into mammalian cells. They overcame the inflammatory activation and rapid degradation of mRNA by modifying the RNA so that it could resist quick breakdown and avoid activating RNA sensors. Despite skepticism from others, Drs. Karikó and Weissman saw the potential of RNA therapeutics for vaccines and other applications and the data kept leading them forward. However, one major challenge remained: how to introduce the mRNA into the body in a way that it would be protected from degradation, and could enter into the cells for protein production.

Dr. Cullis had been working with such packaging systems for the past 50 years. Dr. Cullis is a pioneer in lipid chemistry and the formation of lipid nanoparticles (LNP). From his foundational work, many different clinical applications of LNPs have been developed, such as delivering anticancer drugs to cancer tissues while limiting toxicity in normal tissues. In the case of mRNA the LNP are designed to form a protective bubble around the mRNA and enable delivery to the interior of target cells. The LNP technology is critical to the potency of mRNA vaccines.

Following the emergence of the SARS-CoV2 virus, various teams around the world began working on potential vaccines using the knowledge gained about the mRNA and lipid nanoparticle through decades. The idea for both the Pfizer/BioNTech and Moderna vaccines was to introduce modified mRNA molecules into the body via LNPs to briefly instruct human cells to produce the coronavirus’ spike protein. The LNP-activated immune system would recognize the encoded viral protein and develop antibodies and immune memory so that the immune system would attack the coronavirus when entering the body.

The Impact:

The work of Drs. Karikó, Weissman and Cullis enabled the rapid availability of highly effective and safe COVID-19 mRNA vaccines, which has become an important tool for the control of COVID-19 pandemic. Importantly their pivotal discoveries also have the potential to revolutionize the future delivery of effective and safe vaccines, therapeutics and gene therapies. The success of the mRNA vaccines for COVID-19 suggests paths forward for similar vaccines for viral threats like influenza or HIV. Clinical trials are already underway to test mRNA vaccines to prevent diseases, caused by Zika virus, chikungunya and rabies infections.

The COVID-19 mRNA vaccines developed by Pfizer/BioNTech and Moderna are built on over 30 years of established scientific research and highlight the importance of basic and applied research, and international collaboration.

Les travaux:

Le travail indépendant et collaboratif de Daniel Drucker, Joel Habener et Jens Holst a amélioré notre compréhension du fonctionnement de nos organes gastro-intestinaux et a créé de nouvelles classes de médicaments pour le traitement des troubles métaboliques, en particulier le diabète de type 2, l’obésité et le syndrome de l’intestin court.

Les Drs Drucker, Habener et Holst ont découvert des hormones appelées peptides de type glucagon (GLP-1 et -2) qui contrôlent les niveaux d’insuline et de glucagon, lesquels agissent ensemble pour maintenir des taux de sucre sains. Ils ont élucidé leur biologie et leur fonction physiologique, et ont joué un rôle essentiel dans la conception et l’essai de thérapies éclairées par leurs découvertes initiales et subséquentes.

Ces trois scientifiques sont récompensés pour un ensemble de travaux ayant eu un impact significatif sur le domaine du diabète et du syndrome de l’intestin court, mais ils sont également reconnus pour leurs découvertes individuelles qui sous-tendent les résultats translationnels.

Dans les années 1970, le Dr Holst a observé que des patients en chirurgie intestinale présentaient des pics d’insuline et des baisses de glycémie sanguine après les repas, ce qui l’a conduit à conclure qu’une incrétine, identifiée par la suite comme GLP-1, avec l’insuline et le glucagon, était responsable de la stimulation gastro-intestinale induite par le glucose de la sécrétion d’insuline qui provoquait les changements dans le taux de glycémie.

À peu près au même moment, le Dr Habener a utilisé des cellules pancréatiques de la lotte de mer pour démontrer que le glucagon et la somatostatine étaient codés dans les cellules pancréatiques sous forme d’hormones précurseurs de plus grande taille. Au cours d’études supplémentaires sur des mammifères, il a découvert deux nouvelles hormones liées au glucagon, appelées GLP-1 et GLP-2.

Le Dr Drucker, membre du laboratoire du Dr Habener dans les années 1980, a décrit le traitement du proglucagon et la biologie de l’action du GLP-1 sur les cellules productrices d’insuline, ce qui a conduit au développement de plusieurs types de traitement pour le diabète de type 2. En collaboration avec le Dr Holst, travaillant principalement sur des humains, ils ont montré que lorsque la nourriture est ingérée, le GLP-1 est libéré dans le flux sanguin à partir de cellules de l’intestin, augmentant la libération d’insuline et supprimant le glucagon.

Les travaux de leurs laboratoires et d’autres ont conduit à l’élaboration de nouvelles thérapies pour contrôler la sécrétion d’insuline dans le diabète de type 2, basées sur la compréhension de l’action du GLP1 et de son métabolisme par l’enzyme DPP4, ce qui a conduit directement au développement des inhibiteurs de la DPP-4 pour le traitement du diabète.

Le Dr Drucker a découvert les premières actions du GLP-2 en tant que facteur de croissance intestinale, et les Drs Drucker et Holst ont largement caractérisé ses mécanismes d’action chez les animaux et les humains. Le premier analogue du GLP-2 (teduglutide) a été approuvé pour utilisation clinique dans le traitement du syndrome de l’intestin court en 2012.

L’impact:

Ensemble, Les Drs Drucker, Habener et Holst ont apporté des contributions majeures à l’endocrinologie et ont fait évoluer le traitement des maladies métaboliques et gastro-intestinales. Leur travail est à la fois fondamental et translationnel, et constitue un véritable exemple de recherche progressant du laboratoire au chevet du patient.

Les thérapies GLP-1 ont été efficaces dans le traitement du diabète de type 2 et, plus récemment, dans le traitement de l’obésité en atténuant l’appétit. Les recherches des Drs Drucker et Holst sur la fonction du GLP-2 et son rôle en tant que facteur de croissance intestinale ont aidé au développement de traitements pour la maladie de l’intestin court, réduisant ainsi le besoin de recourir à des sondes d’alimentation pour nourrir les enfants et les adultes atteints de la maladie.

À ce jour, plus de 100 millions de personnes souffrant de diabète de type 2 ont été traitées avec un analogue du GLP-1 ou un inhibiteur de la DPP-4.

The Work:

Drs. Guan and Peiris began collaborating at The University of Hong Kong in the aftermath of the H5N1 avian flu outbreak in Hong Kong. They initiated seminal studies of the underlying causes of H5 virus pathogenicity, the evolution of the H5N1 virus, and developed a highly effective monitoring and surveillance program of avian and swine influenza strains. Through their research Guan and Peiris established that live poultry markets in southern China and Hong Kong were the source of the virus spreading to humans, where it exhibited up to 60% lethality in infected persons. This work led to the temporary closure of the live poultry markets and cessation of animal to human transmission. Their subsequent work established new protocols for periodic live poultry market closures, emptying markets of poultry overnight to reduce virus amplification within these markets and the appropriate use of poultry vaccines to protect both poultry and people in Hong Kong from H5N1 infections. They have made major contributions towards understanding the emergence, transmission, epidemiology and pathogenesis of highly pathogenic avian influenzas including H5N1, H9N2, H6N1, H7N9, H5Nx and others and have provided evidence-based options for control of avian influenza viruses in Asia.

In 2003, following the emergence of novel coronavirus, SARS (severe acute respiratory syndrome) in China, Peiris led the team that first identified the virus responsible for the syndrome, the SARS-CoV-1 coronavirus, elucidating its pathogenesis, transmission, and quickly developed a diagnostic test which was then shared internationally. Meanwhile, Guan’s team identified the human infectious source and zoonotic interface of SARS in the wild animal markets in Guangdong, China in 2003 and identified the human infectious source of MERS (Middle East Respiratory Syndrome) in Saudi Arabia in 2015. Guan’s research accelerated advocacy of the closure of wild game animal markets, averting a potential recurrence of SARS in 2004.

The Impact:

Guan and Peiris’ investigations into the emergence and evolution of animal influenza H5 strains (and other H and N subtypes) and their role in identifying the SARS coronavirus, mode of transmission, risk factors, virus infectivity and period of infectivity, and identifying the original animal source were critical in the successful response to the outbreak.

In the case of SARS, which was causing up to 10% lethality in infected persons, their open sharing of information with the World Health Organization (WHO) and broader international community directly resulted in the rapid control of the disease. The establishment of the role of wild game animal markets in the transmission of the virus was pivotal in the decision by local Guangdong authorities to discontinue such markets to prevent future outbreaks of this or another emerging zoonosis. The isolation and characterization of the causative agent of SARS as a novel coronavirus and quick development of a diagnostic test of the virus in humans directly influenced public health policy to effectively monitor and control the spread of the disease.

Guan and Peiris’ comprehensive strategies for surveillance, monitoring, identifying the human infectious source, investigation, diagnosis and control of emerging infectious disease outbreaks continue to provide critical guidance and insight for countries throughout Asia and the world, including the 2009 swine flu pandemic, Middle East Respiratory Syndrome (MERS), and the COVID-19 pandemic.

Les travaux:

Le travail indépendant et collaboratif de Daniel Drucker, Joel Habener et Jens Holst a amélioré notre compréhension du fonctionnement de nos organes gastro-intestinaux et a créé de nouvelles classes de médicaments pour le traitement des troubles métaboliques, en particulier le diabète de type 2, l’obésité et le syndrome de l’intestin court.

Les Drs Drucker, Habener et Holst ont découvert des hormones appelées peptides de type glucagon (GLP-1 et -2) qui contrôlent les niveaux d’insuline et de glucagon, lesquels agissent ensemble pour maintenir des taux de sucre sains. Ils ont élucidé leur biologie et leur fonction physiologique, et ont joué un rôle essentiel dans la conception et l’essai de thérapies éclairées par leurs découvertes initiales et subséquentes.

Ces trois scientifiques sont récompensés pour un ensemble de travaux ayant eu un impact significatif sur le domaine du diabète et du syndrome de l’intestin court, mais ils sont également reconnus pour leurs découvertes individuelles qui sous-tendent les résultats translationnels.

Dans les années 1970, le Dr Holst a observé que des patients en chirurgie intestinale présentaient des pics d’insuline et des baisses de glycémie sanguine après les repas, ce qui l’a conduit à conclure qu’une incrétine, identifiée par la suite comme GLP-1, avec l’insuline et le glucagon, était responsable de la stimulation gastro-intestinale induite par le glucose de la sécrétion d’insuline qui provoquait les changements dans le taux de glycémie.

À peu près au même moment, le Dr Habener a utilisé des cellules pancréatiques de la lotte de mer pour démontrer que le glucagon et la somatostatine étaient codés dans les cellules pancréatiques sous forme d’hormones précurseurs de plus grande taille. Au cours d’études supplémentaires sur des mammifères, il a découvert deux nouvelles hormones liées au glucagon, appelées GLP-1 et GLP-2.

Le Dr Drucker, membre du laboratoire du Dr Habener dans les années 1980, a décrit le traitement du proglucagon et la biologie de l’action du GLP-1 sur les cellules productrices d’insuline, ce qui a conduit au développement de plusieurs types de traitement pour le diabète de type 2. En collaboration avec le Dr Holst, travaillant principalement sur des humains, ils ont montré que lorsque la nourriture est ingérée, le GLP-1 est libéré dans le flux sanguin à partir de cellules de l’intestin, augmentant la libération d’insuline et supprimant le glucagon.

Les travaux de leurs laboratoires et d’autres ont conduit à l’élaboration de nouvelles thérapies pour contrôler la sécrétion d’insuline dans le diabète de type 2, basées sur la compréhension de l’action du GLP1 et de son métabolisme par l’enzyme DPP4, ce qui a conduit directement au développement des inhibiteurs de la DPP-4 pour le traitement du diabète.

Le Dr Drucker a découvert les premières actions du GLP-2 en tant que facteur de croissance intestinale, et les Drs Drucker et Holst ont largement caractérisé ses mécanismes d’action chez les animaux et les humains. Le premier analogue du GLP-2 (teduglutide) a été approuvé pour utilisation clinique dans le traitement du syndrome de l’intestin court en 2012.

L’impact:

Ensemble, Les Drs Drucker, Habener et Holst ont apporté des contributions majeures à l’endocrinologie et ont fait évoluer le traitement des maladies métaboliques et gastro-intestinales. Leur travail est à la fois fondamental et translationnel, et constitue un véritable exemple de recherche progressant du laboratoire au chevet du patient.

Les thérapies GLP-1 ont été efficaces dans le traitement du diabète de type 2 et, plus récemment, dans le traitement de l’obésité en atténuant l’appétit. Les recherches des Drs Drucker et Holst sur la fonction du GLP-2 et son rôle en tant que facteur de croissance intestinale ont aidé au développement de traitements pour la maladie de l’intestin court, réduisant ainsi le besoin de recourir à des sondes d’alimentation pour nourrir les enfants et les adultes atteints de la maladie.

À ce jour, plus de 100 millions de personnes souffrant de diabète de type 2 ont été traitées avec un analogue du GLP-1 ou un inhibiteur de la DPP-4.

The Work:

Drs. Guan and Peiris began collaborating at The University of Hong Kong in the aftermath of the H5N1 avian flu outbreak in Hong Kong. They initiated seminal studies of the underlying causes of H5 virus pathogenicity, the evolution of the H5N1 virus, and developed a highly effective monitoring and surveillance program of avian and swine influenza strains. Through their research Guan and Peiris established that live poultry markets in southern China and Hong Kong were the source of the virus spreading to humans, where it exhibited up to 60% lethality in infected persons. This work led to the temporary closure of the live poultry markets and cessation of animal to human transmission. Their subsequent work established new protocols for periodic live poultry market closures, emptying markets of poultry overnight to reduce virus amplification within these markets and the appropriate use of poultry vaccines to protect both poultry and people in Hong Kong from H5N1 infections. They have made major contributions towards understanding the emergence, transmission, epidemiology and pathogenesis of highly pathogenic avian influenzas including H5N1, H9N2, H6N1, H7N9, H5Nx and others and have provided evidence-based options for control of avian influenza viruses in Asia.

In 2003, following the emergence of novel coronavirus, SARS (severe acute respiratory syndrome) in China, Peiris led the team that first identified the virus responsible for the syndrome, the SARS-CoV-1 coronavirus, elucidating its pathogenesis, transmission, and quickly developed a diagnostic test which was then shared internationally. Meanwhile, Guan’s team identified the human infectious source and zoonotic interface of SARS in the wild animal markets in Guangdong, China in 2003 and identified the human infectious source of MERS (Middle East Respiratory Syndrome) in Saudi Arabia in 2015. Guan’s research accelerated advocacy of the closure of wild game animal markets, averting a potential recurrence of SARS in 2004.

The Impact:

Guan and Peiris’ investigations into the emergence and evolution of animal influenza H5 strains (and other H and N subtypes) and their role in identifying the SARS coronavirus, mode of transmission, risk factors, virus infectivity and period of infectivity, and identifying the original animal source were critical in the successful response to the outbreak.

In the case of SARS, which was causing up to 10% lethality in infected persons, their open sharing of information with the World Health Organization (WHO) and broader international community directly resulted in the rapid control of the disease. The establishment of the role of wild game animal markets in the transmission of the virus was pivotal in the decision by local Guangdong authorities to discontinue such markets to prevent future outbreaks of this or another emerging zoonosis. The isolation and characterization of the causative agent of SARS as a novel coronavirus and quick development of a diagnostic test of the virus in humans directly influenced public health policy to effectively monitor and control the spread of the disease.

Guan and Peiris’ comprehensive strategies for surveillance, monitoring, identifying the human infectious source, investigation, diagnosis and control of emerging infectious disease outbreaks continue to provide critical guidance and insight for countries throughout Asia and the world, including the 2009 swine flu pandemic, Middle East Respiratory Syndrome (MERS), and the COVID-19 pandemic.

Les travaux:

Le travail indépendant et collaboratif de Daniel Drucker, Joel Habener et Jens Holst a amélioré notre compréhension du fonctionnement de nos organes gastro-intestinaux et a créé de nouvelles classes de médicaments pour le traitement des troubles métaboliques, en particulier le diabète de type 2, l’obésité et le syndrome de l’intestin court.

Les Drs Drucker, Habener et Holst ont découvert des hormones appelées peptides de type glucagon (GLP-1 et -2) qui contrôlent les niveaux d’insuline et de glucagon, lesquels agissent ensemble pour maintenir des taux de sucre sains. Ils ont élucidé leur biologie et leur fonction physiologique, et ont joué un rôle essentiel dans la conception et l’essai de thérapies éclairées par leurs découvertes initiales et subséquentes.

Ces trois scientifiques sont récompensés pour un ensemble de travaux ayant eu un impact significatif sur le domaine du diabète et du syndrome de l’intestin court, mais ils sont également reconnus pour leurs découvertes individuelles qui sous-tendent les résultats translationnels.

Dans les années 1970, le Dr Holst a observé que des patients en chirurgie intestinale présentaient des pics d’insuline et des baisses de glycémie sanguine après les repas, ce qui l’a conduit à conclure qu’une incrétine, identifiée par la suite comme GLP-1, avec l’insuline et le glucagon, était responsable de la stimulation gastro-intestinale induite par le glucose de la sécrétion d’insuline qui provoquait les changements dans le taux de glycémie.

À peu près au même moment, le Dr Habener a utilisé des cellules pancréatiques de la lotte de mer pour démontrer que le glucagon et la somatostatine étaient codés dans les cellules pancréatiques sous forme d’hormones précurseurs de plus grande taille. Au cours d’études supplémentaires sur des mammifères, il a découvert deux nouvelles hormones liées au glucagon, appelées GLP-1 et GLP-2.

Le Dr Drucker, membre du laboratoire du Dr Habener dans les années 1980, a décrit le traitement du proglucagon et la biologie de l’action du GLP-1 sur les cellules productrices d’insuline, ce qui a conduit au développement de plusieurs types de traitement pour le diabète de type 2. En collaboration avec le Dr Holst, travaillant principalement sur des humains, ils ont montré que lorsque la nourriture est ingérée, le GLP-1 est libéré dans le flux sanguin à partir de cellules de l’intestin, augmentant la libération d’insuline et supprimant le glucagon.

Les travaux de leurs laboratoires et d’autres ont conduit à l’élaboration de nouvelles thérapies pour contrôler la sécrétion d’insuline dans le diabète de type 2, basées sur la compréhension de l’action du GLP1 et de son métabolisme par l’enzyme DPP4, ce qui a conduit directement au développement des inhibiteurs de la DPP-4 pour le traitement du diabète.

Le Dr Drucker a découvert les premières actions du GLP-2 en tant que facteur de croissance intestinale, et les Drs Drucker et Holst ont largement caractérisé ses mécanismes d’action chez les animaux et les humains. Le premier analogue du GLP-2 (teduglutide) a été approuvé pour utilisation clinique dans le traitement du syndrome de l’intestin court en 2012.

L’impact:

Ensemble, Les Drs Drucker, Habener et Holst ont apporté des contributions majeures à l’endocrinologie et ont fait évoluer le traitement des maladies métaboliques et gastro-intestinales. Leur travail est à la fois fondamental et translationnel, et constitue un véritable exemple de recherche progressant du laboratoire au chevet du patient.

Les thérapies GLP-1 ont été efficaces dans le traitement du diabète de type 2 et, plus récemment, dans le traitement de l’obésité en atténuant l’appétit. Les recherches des Drs Drucker et Holst sur la fonction du GLP-2 et son rôle en tant que facteur de croissance intestinale ont aidé au développement de traitements pour la maladie de l’intestin court, réduisant ainsi le besoin de recourir à des sondes d’alimentation pour nourrir les enfants et les adultes atteints de la maladie.

À ce jour, plus de 100 millions de personnes souffrant de diabète de type 2 ont été traitées avec un analogue du GLP-1 ou un inhibiteur de la DPP-4.

The Work:

Dr. King’s first breakthrough was in molecular evolution and population genetics. Her research as a PhD student suggested that the differences between humans and chimpanzees are due to a small number of mutations affecting gene regulation and the timing of gene expression, rather than accumulation of differences in protein-coding sequences.

King’s work evolved to focus on proving the existence of inherited susceptibility to breast cancer and identifying BRCA1 as the first gene responsible for it. Her group studied families in which many women developed breast or ovarian cancer. First, based on mathematical modeling, King hypothesized that severe inherited mutations in a single gene could be responsible for breast cancer in some women. At the time, this hypothesis was considered far-fetched and very unlikely.

Then based on this hypothesis, King proved the gene’s existence by mapping the still-hypothetical gene to a specific chromosomal location. She named the gene BRCA1. The idea was no longer far-fetched and an international “race” of four years ensued to clone the gene.

After the gene was cloned, King and her colleagues developed and deployed next-generation sequencing strategies to identify mutations in BRCA1 and its sister genes responsible for multiple forms of inherited cancer. She and many others have applied the same approach to identification of genes with major impact on other complex diseases.

The Impact:

Dr. King’s discovery has transformed the diagnosis, drug development, and treatment of inherited breast and ovarian cancer. The identification of BRCA1 — and subsequently BRCA2 — has made it possible to diagnose whether a woman in an affected family is at extremely high risk of developing breast and ovarian cancer, enabling her to pursue preventative treatment.

King’s passion for gene discovery integrated tools from genetics, statistics, mathematics, epidemiology, molecular biology, genomics and clinical medicine. Her revolutionary approach to gene discovery has had an impact on many other diseases, ranging from prostate cancer to inherited hearing loss to schizophrenia. King is also a pioneer in the development of DNA sequencing for the identification of victims of human rights’ violations.

The Work:

Dr. Eisenhauer’s research has transformed the fields of cancer clinical trials and cancer drug delivery. Her fundamental contributions to the clinical evaluation of new anti-cancer agents, as well as cancer research strategy and clinical trials development, have been critical in the development of new treatments for ovarian cancer, malignant melanoma and brain tumours. She is credited with developing new methodologies for the delivery of Taxol, one of the most important cancer drugs in the world, which maintained the drug’s efficacy and reduced toxic side effects to cancer patients. This shorter, safer method to deliver the drug has become the international standard, transforming the experience and outcomes of millions of patients worldwide.

Dr. Eisenhauer’s extraordinary contributions extend to impactful national and international leadership roles including the founding in 1982 and subsequent direction of the Investigational New Drug Program (IND) of the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG), now the Canadian Cancer Trials Group. Dr. Eisenhauer also co-led the Methodology for the Development of Innovative Cancer Therapies International Task Force where she developed recommendations for the design and endpoints for trials of novel targeted cancer agents. As well she led the creation of the first collaborative cancer research strategy for Canada in her role as co-Chair of the Canadian Cancer Research Alliance, convened the first Summit to create a Tobacco Endgame for Canada and was inaugural Expert Lead for Research in the Canadian Partnership against Cancer.

The Impact:

Dr. Eisenhauer’s commitment to the advancement of cancer therapy, supportive care and prevention is unparalleled. Her extensive research contributions and leadership within the field of cancer care in Canada have influenced and advanced the conduct of clinical trials internationally. Her work has expanded the understanding of therapeutic interventions and has led to new standards of cancer treatment for patients in Canada and around the world.

Les travaux:

Les Drs Guan et Peiris ont commencé à collaborer à l’Université de Hong Kong à la suite de l’épidémie de grippe aviaire H5N1 à Hong Kong. Ils ont lancé des études pionnières sur les causes sous-jacentes de la pathogénicité du virus H5 et l’évolution du virus H5N1, et ils ont élaboré un programme de suivi et de surveillance très efficace des souches de grippe aviaire et porcine. Au fil de leurs recherches, les Drs Guan et Peiris ont établi que les marchés de volailles vivantes du sud de la Chine et de Hong Kong étaient à l’origine de la propagation du virus aux humains, où il présentait jusqu’à 60 % de létalité chez les personnes infectées. Ces travaux ont conduit à la fermeture temporaire des marchés de volailles vivantes et à l’arrêt de la transmission animal-humain. Leurs travaux subséquents ont établi de nouveaux protocoles pour la fermeture périodique des marchés de volaille vivante, vidant les marchés de volaille du jour au lendemain en vue de réduire l’amplification du virus sur ces marchés, doublé de l’utilisation appropriée des vaccins pour volailles afin de protéger à la fois les volailles et les habitants de Hong Kong contre les infections au H5N1. Ils ont fait des contributions majeures à la compréhension de l’émergence, de la transmission, de l’épidémiologie et de la pathogenèse des grippes aviaires hautement pathogènes, notamment H5N1, H9N2, H6N1, H7N9, H5Nx et d’autres, et ils ont offert des solutions fondées sur des données probantes pour lutter contre les virus de la grippe aviaire en Asie.

En 2003, suite à l’émergence du nouveau coronavirus, le SRAS (syndrome respiratoire aigu sévère) en Chine, le Dr Peiris a dirigé l’équipe qui a d’abord identifié le virus responsable du syndrome, le coronavirus SRAS-CoV-1, élucidant sa pathogenèse, sa transmission, et il a rapidement mis au point un test de diagnostic qui a ensuite été partagé à l’échelle internationale. Simultanément, l’équipe du Dr Guan a identifié en 2003 la source de l’infection humaine et l’interface zoonotique du SRAS sur les marchés d’animaux sauvages du Guangdong, en Chine, et il a identifié la source de l’infection humaine du SRMO (syndrome respiratoire du Moyen-Orient) en Arabie saoudite en 2015. Les recherches du Dr Guan ont accéléré le mouvement en faveur de la fermeture des marchés d’animaux sauvages, évitant une éventuelle récidive du SRAS en 2004.

L’impact:

Les recherches des Drs Guan et Peiris sur l’émergence et l’évolution des souches animales des grippes H5 (et d’autres sous-types H et N) et leur rôle dans l’identification du coronavirus SRAS, de son mode de transmission, des facteurs de risque, de l’infectiosité du virus et de sa période d’infectiosité, ainsi que l’identification de la source animale d’origine, ont joué un rôle clé dans la réussite de la réponse à l’épidémie.

Dans le cas du SRAS, dont la létalité atteignait jusqu’à 10 % chez les personnes infectées, le fait qu’ils aient ouvertement partagé l’information avec l’Organisation mondiale de la Santé (OMS) et la communauté internationale plus vaste a directement permis un contrôle rapide de la maladie. L’établissement du rôle des marchés d’animaux sauvages dans la transmission du virus a joué un rôle crucial dans la décision des autorités locales du Guangdong de mettre fin à ces marchés afin d’éviter de futures flambées de cette zoonose ou d’une autre zoonose émergente. L’identification et la caractérisation de l’agent causal du SRAS en tant que nouveau coronavirus et le développement rapide d’un test de diagnostic du virus chez l’homme ont directement influencé la politique de santé publique en vue de surveiller et de contrôler efficacement la propagation de la maladie.

Les stratégies globales des Drs Guan et Peiris pour la surveillance, le suivi, l’identification de la source d’infection humaine, l’examen, le diagnostic et le contrôle des flambées de maladies infectieuses émergentes ont continué de guider et d’éclairer fondamentalement les pays d’Asie et du monde, notamment pour la pandémie de grippe porcine de 2009, le syndrome respiratoire du Moyen-Orient (SRMO) et la pandémie de COVID-19.

The Work:

The independent and collaborative work of Daniel Drucker, Joel Habener and Jens Holst enhanced our understanding of how our gastrointestinal organs function and created new classes of drugs for the treatment of metabolic disorders, specifically type 2 diabetes, obesity and short bowel syndrome.

Drucker, Habener and Holst discovered hormones called glucagon-like peptides (GLP-1 and -2) which control the levels of Insulin and glucagon which work together to maintain healthy sugar levels. They elucidated their biology and physiological function and played critical roles in the design and testing of therapies informed by their initial and subsequent discoveries

These three scientists are awarded for a combined body of work with significant impact on the field of diabetes and short bowel syndrome but are also recognized for their individual discoveries that underpin the translational results.

In the 1970s, Holst recorded intestinal surgery patients experiencing insulin spikes and drops in blood sugar after meals, leading him to conclude that an incretin, subsequently identified as
GLP-1, along with insulin and glucagon was responsible for the glucose-induced gastrointestinal stimulation of insulin secretion that caused the changes in blood sugar levels.

Around the same time, Habener used pancreatic cells from anglerfish to demonstrate that glucagon and somatostatin were encoded in the pancreatic cells as larger, precursor hormones. During additional mammal studies he discovered two new hormones related to glucagon which are known as GLP-1 and GLP-2.

Drucker, a fellow in Habener’s lab in the 1980s, outlined the processing of proglucagon and the biology of GLP-1 action on insulin-producing cells, which led to the development of multiple types of treatments for type 2 diabetes. Together with Holst, working mostly in people, they showed that when food is ingested, GLP-1 is released into the bloodstream from cells in the gut increasing insulin release and suppressing glucagon.

Work from their labs and others led to the development of novel therapeutics to control insulin secretion in Type 2 diabetes based on understanding the action of GLP1 and its metabolism by the enzyme, DPP4, leading directly to the development of the DPP-4 inhibitors for diabetes therapy.

Drucker discovered the first actions of GLP-2 as a gut growth factor and both Drucker and Holst extensively characterized its mechanisms of action in animals and humans. The first GLP-2 analogue (teduglutide) was approved for clinical use in the treatment of short bowel syndrome in 2012.

The Impact:

Together, Drucker, Habener and Holst made major contributions to endocrinology and changed the treatment of metabolic and gastrointestinal diseases. Their work is both basic and translational, a true example of bench to bedside research.

GLP-1 therapies have been effective in the treatment of type 2 diabetes and more recently, as a treatment of obesity to reduce appetite. Drucker and Holst’s research on the function of GLP-2 and its role as an intestinal growth factor helped develop treatments for short bowel disease, decreasing the need for feeding tubes to provide nutrition in children and adults with the condition.

To date, over 100 million people with type 2 diabetes have been treated with a GLP-1 analogue or a DPP-4 inhibitor.

The Work:

The independent and collaborative work of Daniel Drucker, Joel Habener and Jens Holst enhanced our understanding of how our gastrointestinal organs function and created new classes of drugs for the treatment of metabolic disorders, specifically type 2 diabetes, obesity and short bowel syndrome.

Drucker, Habener and Holst discovered hormones called glucagon-like peptides (GLP-1 and -2) which control the levels of Insulin and glucagon which work together to maintain healthy sugar levels. They elucidated their biology and physiological function and played critical roles in the design and testing of therapies informed by their initial and subsequent discoveries

These three scientists are awarded for a combined body of work with significant impact on the field of diabetes and short bowel syndrome but are also recognized for their individual discoveries that underpin the translational results.

In the 1970s, Holst recorded intestinal surgery patients experiencing insulin spikes and drops in blood sugar after meals, leading him to conclude that an incretin, subsequently identified as
GLP-1, along with insulin and glucagon was responsible for the glucose-induced gastrointestinal stimulation of insulin secretion that caused the changes in blood sugar levels.

Around the same time, Habener used pancreatic cells from anglerfish to demonstrate that glucagon and somatostatin were encoded in the pancreatic cells as larger, precursor hormones. During additional mammal studies he discovered two new hormones related to glucagon which are known as GLP-1 and GLP-2.

Drucker, a fellow in Habener’s lab in the 1980s, outlined the processing of proglucagon and the biology of GLP-1 action on insulin-producing cells, which led to the development of multiple types of treatments for type 2 diabetes. Together with Holst, working mostly in people, they showed that when food is ingested, GLP-1 is released into the bloodstream from cells in the gut increasing insulin release and suppressing glucagon.

Work from their labs and others led to the development of novel therapeutics to control insulin secretion in Type 2 diabetes based on understanding the action of GLP1 and its metabolism by the enzyme, DPP4, leading directly to the development of the DPP-4 inhibitors for diabetes therapy.

Drucker discovered the first actions of GLP-2 as a gut growth factor and both Drucker and Holst extensively characterized its mechanisms of action in animals and humans. The first GLP-2 analogue (teduglutide) was approved for clinical use in the treatment of short bowel syndrome in 2012.

The Impact:

Together, Drucker, Habener and Holst made major contributions to endocrinology and changed the treatment of metabolic and gastrointestinal diseases. Their work is both basic and translational, a true example of bench to bedside research.

GLP-1 therapies have been effective in the treatment of type 2 diabetes and more recently, as a treatment of obesity to reduce appetite. Drucker and Holst’s research on the function of GLP-2 and its role as an intestinal growth factor helped develop treatments for short bowel disease, decreasing the need for feeding tubes to provide nutrition in children and adults with the condition.

To date, over 100 million people with type 2 diabetes have been treated with a GLP-1 analogue or a DPP-4 inhibitor.

Les travaux:

Les Drs Guan et Peiris ont commencé à collaborer à l’Université de Hong Kong à la suite de l’épidémie de grippe aviaire H5N1 à Hong Kong. Ils ont lancé des études pionnières sur les causes sous-jacentes de la pathogénicité du virus H5 et l’évolution du virus H5N1, et ils ont élaboré un programme de suivi et de surveillance très efficace des souches de grippe aviaire et porcine. Au fil de leurs recherches, les Drs Guan et Peiris ont établi que les marchés de volailles vivantes du sud de la Chine et de Hong Kong étaient à l’origine de la propagation du virus aux humains, où il présentait jusqu’à 60 % de létalité chez les personnes infectées. Ces travaux ont conduit à la fermeture temporaire des marchés de volailles vivantes et à l’arrêt de la transmission animal-humain. Leurs travaux subséquents ont établi de nouveaux protocoles pour la fermeture périodique des marchés de volaille vivante, vidant les marchés de volaille du jour au lendemain en vue de réduire l’amplification du virus sur ces marchés, doublé de l’utilisation appropriée des vaccins pour volailles afin de protéger à la fois les volailles et les habitants de Hong Kong contre les infections au H5N1. Ils ont fait des contributions majeures à la compréhension de l’émergence, de la transmission, de l’épidémiologie et de la pathogenèse des grippes aviaires hautement pathogènes, notamment H5N1, H9N2, H6N1, H7N9, H5Nx et d’autres, et ils ont offert des solutions fondées sur des données probantes pour lutter contre les virus de la grippe aviaire en Asie.

En 2003, suite à l’émergence du nouveau coronavirus, le SRAS (syndrome respiratoire aigu sévère) en Chine, le Dr Peiris a dirigé l’équipe qui a d’abord identifié le virus responsable du syndrome, le coronavirus SRAS-CoV-1, élucidant sa pathogenèse, sa transmission, et il a rapidement mis au point un test de diagnostic qui a ensuite été partagé à l’échelle internationale. Simultanément, l’équipe du Dr Guan a identifié en 2003 la source de l’infection humaine et l’interface zoonotique du SRAS sur les marchés d’animaux sauvages du Guangdong, en Chine, et il a identifié la source de l’infection humaine du SRMO (syndrome respiratoire du Moyen-Orient) en Arabie saoudite en 2015. Les recherches du Dr Guan ont accéléré le mouvement en faveur de la fermeture des marchés d’animaux sauvages, évitant une éventuelle récidive du SRAS en 2004.

L’impact:

Les recherches des Drs Guan et Peiris sur l’émergence et l’évolution des souches animales des grippes H5 (et d’autres sous-types H et N) et leur rôle dans l’identification du coronavirus SRAS, de son mode de transmission, des facteurs de risque, de l’infectiosité du virus et de sa période d’infectiosité, ainsi que l’identification de la source animale d’origine, ont joué un rôle clé dans la réussite de la réponse à l’épidémie.

Dans le cas du SRAS, dont la létalité atteignait jusqu’à 10 % chez les personnes infectées, le fait qu’ils aient ouvertement partagé l’information avec l’Organisation mondiale de la Santé (OMS) et la communauté internationale plus vaste a directement permis un contrôle rapide de la maladie. L’établissement du rôle des marchés d’animaux sauvages dans la transmission du virus a joué un rôle crucial dans la décision des autorités locales du Guangdong de mettre fin à ces marchés afin d’éviter de futures flambées de cette zoonose ou d’une autre zoonose émergente. L’identification et la caractérisation de l’agent causal du SRAS en tant que nouveau coronavirus et le développement rapide d’un test de diagnostic du virus chez l’homme ont directement influencé la politique de santé publique en vue de surveiller et de contrôler efficacement la propagation de la maladie.

Les stratégies globales des Drs Guan et Peiris pour la surveillance, le suivi, l’identification de la source d’infection humaine, l’examen, le diagnostic et le contrôle des flambées de maladies infectieuses émergentes ont continué de guider et d’éclairer fondamentalement les pays d’Asie et du monde, notamment pour la pandémie de grippe porcine de 2009, le syndrome respiratoire du Moyen-Orient (SRMO) et la pandémie de COVID-19.

The Work:

The independent and collaborative work of Daniel Drucker, Joel Habener and Jens Holst enhanced our understanding of how our gastrointestinal organs function and created new classes of drugs for the treatment of metabolic disorders, specifically type 2 diabetes, obesity and short bowel syndrome.

Drucker, Habener and Holst discovered hormones called glucagon-like peptides (GLP-1 and -2) which control the levels of Insulin and glucagon which work together to maintain healthy sugar levels. They elucidated their biology and physiological function and played critical roles in the design and testing of therapies informed by their initial and subsequent discoveries

These three scientists are awarded for a combined body of work with significant impact on the field of diabetes and short bowel syndrome but are also recognized for their individual discoveries that underpin the translational results.

In the 1970s, Holst recorded intestinal surgery patients experiencing insulin spikes and drops in blood sugar after meals, leading him to conclude that an incretin, subsequently identified as
GLP-1, along with insulin and glucagon was responsible for the glucose-induced gastrointestinal stimulation of insulin secretion that caused the changes in blood sugar levels.

Around the same time, Habener used pancreatic cells from anglerfish to demonstrate that glucagon and somatostatin were encoded in the pancreatic cells as larger, precursor hormones. During additional mammal studies he discovered two new hormones related to glucagon which are known as GLP-1 and GLP-2.

Drucker, a fellow in Habener’s lab in the 1980s, outlined the processing of proglucagon and the biology of GLP-1 action on insulin-producing cells, which led to the development of multiple types of treatments for type 2 diabetes. Together with Holst, working mostly in people, they showed that when food is ingested, GLP-1 is released into the bloodstream from cells in the gut increasing insulin release and suppressing glucagon.

Work from their labs and others led to the development of novel therapeutics to control insulin secretion in Type 2 diabetes based on understanding the action of GLP1 and its metabolism by the enzyme, DPP4, leading directly to the development of the DPP-4 inhibitors for diabetes therapy.

Drucker discovered the first actions of GLP-2 as a gut growth factor and both Drucker and Holst extensively characterized its mechanisms of action in animals and humans. The first GLP-2 analogue (teduglutide) was approved for clinical use in the treatment of short bowel syndrome in 2012.

The Impact:

Together, Drucker, Habener and Holst made major contributions to endocrinology and changed the treatment of metabolic and gastrointestinal diseases. Their work is both basic and translational, a true example of bench to bedside research.

GLP-1 therapies have been effective in the treatment of type 2 diabetes and more recently, as a treatment of obesity to reduce appetite. Drucker and Holst’s research on the function of GLP-2 and its role as an intestinal growth factor helped develop treatments for short bowel disease, decreasing the need for feeding tubes to provide nutrition in children and adults with the condition.

To date, over 100 million people with type 2 diabetes have been treated with a GLP-1 analogue or a DPP-4 inhibitor.

Les travaux:

Les recherches de la Dre Eisenhauer ont transformé les domaines des essais cliniques sur le cancer et de l’administration des médicaments contre le cancer. Sa contribution fondamentale à l’évaluation clinique de nouveaux agents anticancéreux, à la stratégie de recherche sur le cancer et à la mise au point d’essais cliniques, a joué un rôle clé dans le développement de nouveaux traitements pour le cancer de l’ovaire, le mélanome malin et les tumeurs cérébrales. On lui attribue l’élaboration de nouvelles méthodologies pour l’administration de Taxol, l’un des médicaments anticancéreux les plus importants dans le monde, qui ont maintenu l’efficacité du médicament et réduit ses effets secondaires toxiques chez les patients cancéreux. Cette méthode plus brève et plus sûre d’administration du médicament est devenue la norme internationale, transformant l’expérience et les résultats pour des millions de patients à travers le monde.

La contribution exceptionnelle de la Dre Eisenhauer englobe aussi des rôles de leadership clés au plan national et international, y compris la fondation en 1982 et la direction subséquente du Programme des nouvelles drogues de recherche (IND), du Groupe des essais cliniques de l’Institut de recherche de la Société canadienne du cancer (GEC-IRSCC), devenu le Groupe d'essais cliniques du Canada. La Dre Eisenhauer a également codirigé le Groupe de travail international sur la méthodologie de développement de thérapies innovantes contre le cancer, où elle a élaboré des recommandations pour la conception et les critères d’évaluation des essais de nouveaux agents anticancéreux ciblés. En outre, elle a dirigé la création de la première stratégie de recherche collaborative sur le cancer au Canada à titre de coprésidente de l’Alliance canadienne pour la recherche sur le cancer, elle a convoqué le premier Sommet sur la création d’une Stratégie d’échec au tabac au Canada et a été la première spécialiste responsable de la recherche au Partenariat canadien contre le cancer.

L’impact:

L’engagement de la Dre Eisenhauer pour l’avancement de la thérapie anticancéreuse, des soins de soutien et de la prévention est inégalé. Sa vaste contribution à la recherche et son leadership dans le domaine des soins contre le cancer au Canada ont influencé et fait progresser la conduite des essais cliniques à l’échelle internationale. Ses travaux ont fait progresser la compréhension des interventions thérapeutiques et a mené à de nouvelles normes de traitement du cancer pour les patients au Canada et ailleurs dans le monde.

Les travaux:

La première percée de la Dre King touchait l’évolution moléculaire et la génétique des populations. Ses recherches alors qu’elle était doctorante laissaient penser que les différences entre les humains et les chimpanzés sont dues à un petit nombre de mutations affectant la régulation des gènes et le moment de l’expression génique, plutôt qu’à l’accumulation de différences dans les séquences codant pour les protéines.

Les travaux de la Dre King ont évolué pour se concentrer sur la preuve de l’existence d’une susceptibilité héréditaire au cancer du sein et l’identification de BRCA1 comme premier gène responsable de celle-ci. Son groupe a étudié des familles où de nombreuses femmes ont contracté un cancer du sein ou de l’ovaire. Tout d’abord, en recourant à une modélisation mathématique, elle a émis l’hypothèse que de sérieuses mutations héréditaires dans un seul gène pourraient être responsables du cancer du sein chez certaines femmes. À l’époque, cette hypothèse était considérée comme farfelue et très peu probable.

S’appuyant ensuite sur cette hypothèse, la Dre King a prouvé l’existence du gène en cartographiant le gène hypothétique à un site chromosomique spécifique. Elle a nommé ce gène BRCA1. L’idée n’était plus exagérée et une « course » internationale de quatre ans s’ensuivit pour cloner le gène.

Après que le gène ait été cloné, la Dre King et ses collègues ont développé et déployé des stratégies de séquençage de nouvelle génération pour identifier les mutations dans BRCA1 et les gènes apparentés qui sont responsables de multiples formes de cancer héréditaire. Elle et beaucoup d’autres ont appliqué la même approche à l’identification des gènes qui ont une incidence majeure sur d’autres maladies complexes.

L’impact:

La découverte de la Dre King a transformé le diagnostic, la mise au point de médicaments et le traitement du cancer héréditaire du sein et de l’ovaire.

L’identification de BRCA1, et subséquemment de BRCA2, a permis de diagnostiquer si une femme appartenant à une famille touchée présente un risque extrêmement élevé de développer un cancer du sein ou de l’ovaire, ce qui lui permet de suivre un traitement préventif.

La passion de la Dre King pour la découverte de gènes intégrait des outils issus de la génétique, de la statistique, des mathématiques, de l’épidémiologie, de la biologie moléculaire, de la génomique et de la médecine clinique. Son approche révolutionnaire de la découverte génique a eu un impact sur de nombreuses autres maladies, allant du cancer de la prostate à la perte auditive héréditaire et jusqu’à la schizophrénie. La Dre King est également une pionnière du développement du séquençage de l’ADN pour l’identification des victimes de violations des droits humains.

The Work:
Dr. Rouleau has identified over 20 genetic risk factors predisposing to a range of brain disorders, both neurological and psychiatric, involving either neurodevelopmental processes or degenerative events. He has defined a novel disease mechanism for diseases related to repeat expansions that are at play in some of the most severe neurodegenerative conditions. He has significantly contributed to the understanding of the role of de novo variants in autism and schizophrenia. In addition, he has made important advances for various neuropathies, in particular for amyotrophic lateral sclerosis (ALS) where he was involved in the identification of the most prevalent genetic risk factors -which in turn are now the core of innumerable ALS studies worldwide.

Dr. Rouleau has also played a pioneering role in the practice of Open Science (OS), transforming the Montreal Neurological Institute-Hospital (The Neuro) into the first OS institution in the world. The Neuro now uses OS principles to transform research and care and accelerate the development of new treatments for patients through Open Access, Open Data, Open Biobanking, Open Early Drug Discovery and non-restrictive intellectual property.

The Impact:
The identification of genetic risk factors has a number of significant consequences. First, allowing for more accurate genetic counselling, which reduces the burden of disease to affected individuals, parents and society. A revealing case is Andermann syndrome, a severe neurodevelopmental and neurodegenerative condition that was once relatively common in the Saguenay-Lac-St-Jean region of Quebec. Now this disease has almost disappeared from that population. Second, identifying the causative gene allows the development of treatments. For instance, his earlier work on a form of ALS linked to the superoxide dismutase-1 gene (SOD1) opened up studies which are now the focal point of phase 2 clinical studies showing great promise.

By acting as a living lab for the last couple of years, The Neuro is spearheading the practice of Open Science (OS). The Neuro is also engaging stakeholders across Canada with the goal of formal izing a national OS alliance for the neurosciences. Dr. Rouleau's work in OS contributes fundamentally to the transformation of the very ecosystem of science by stimulating new thinking and fostering communities of sharing. Inspired by The Neuro's vision, the global science community is reflecting on current research conventions and collaborative projects, and the momentum for OS is gaining a foothold in organizations and institutions in all corners of the earth.

Les travaux:
L’ONUSIDA estime que 37 millions de personnes vivaient avec le VIH et que 1,8 million de personnes ont contracté le VIH en 2017. En Afrique, où se trouvent plus des deux tiers des personnes vivant avec le VIH, les adolescentes et les jeunes femmes ont les taux les plus élevés de nouvelles infections au VIH. Les messages de prévention ABC (abstinence, soyez fidèle et utilisez des préservatifs) ont eu peu d’impact – en raison de l’inégalité des pouvoirs entre les sexes, les jeunes femmes sont souvent incapables de négocier avec succès l’utilisation du préservatif, d’insister sur la monogamie mutuelle ou de convaincre leurs partenaires masculins de se soumettre à un test de dépistage du VIH.

En réponse à cette crise, Salim et Quarraisha Abdool Karim ont commencé à étudier, il y a une trentaine d’années, les nouvelles technologies de prévention du VIH pour les femmes. Après deux décennies infructueuses, leur persévérance a porté ses fruits lorsqu’ils ont fait la démonstration de principe que les antirétroviraux préviennent l’infection au VIH sexuellement acquise chez les femmes. Leur essai révolutionnaire, CAPRISA 004, a montré que le gel de ténofovir prévient à la fois l’infection par le VIH et l’herpès génital. La découverte a été classée dans le « Top 10 des percées scientifiques de 2010 » par la revue Science. Cette découverte a été présentée par l’ONUSIDA et l’Organisation mondiale de la Santé (OMS) comme l’une des percées scientifiques les plus importantes dans le domaine du sida et a fourni les premières preuves de ce qu’on appelle aujourd’hui la prophylaxie pré-exposition au VIH (PrEP).

Les Abdool Karim ont également élucidé la nature évolutive de l’épidémie de VIH en Afrique, caractérisant les principaux facteurs de risque sociaux, comportementaux et biologiques responsables de la charge disproportionnée du VIH chez les jeunes femmes. Leur identification du « cycle de transmission du VIH », où les adolescentes contractent le VIH au contact d’hommes environ 10 ans plus âgés en moyenne a façonné les politiques de l’ONUSIDA en matière de prévention du VIH en Afrique.

L’impact:
CAPRISA 004 et plusieurs essais cliniques sur le ténofovir oral ont conduit l’OMS à recommander, quelques années plus tard, une pilule quotidienne contenant du ténofovir pour la PPrE comme outil standard de prévention du VIH pour toutes les personnes à haut risque. Plusieurs pays africains font partie des 68 pays sur tous les continents qui offrent actuellement la PPrE comme mesure de prévention du VIH. Les recherches entreprises en Afrique par ce couple sud-africain ont joué un rôle clé dans l’élaboration de la réponse locale et mondiale à l’épidémie de VIH.

Les travaux:
La Dre Fuchs a utilisé la peau pour étudier comment les tissus de notre corps sont capables de remplacer les cellules mourantes et de réparer les plaies. La peau doit se régénérer constamment pour se protéger de la déshydratation et des microbes nuisibles. Dans ses recherches, Fuchs a montré que cela est opéré par une population résidente de cellules souches adultes qui génère continuellement une coquille de cellules indestructibles qui recouvrent la surface de notre corps.

Dans ses premières recherches, la Dre Fuchs a identifié les protéines – les kératines – qui produisent l’armature des blocs structurants de la peau, et a montré que les mutations des kératines sont responsables d’un groupe de maladies ‘boursouflantes’ chez l’homme. Dans ses travaux ultérieurs, la Dre Fuchs a identifié les signaux qui incitent les cellules souches de la peau à fabriquer des tissus et leur indiquent quand s’arrêter. En étudiant ces processus, elle a constaté que les cancers détournent les mécanismes fondamentaux que les cellules souches tissulaires utilisent pour réparer les plaies. Son équipe a poursuivi dans cette voie parallèle et isolé et caractérisé les cellules souches malignes qui sont responsables de la propagation d’un type de cancer appelé « carcinome épidermoïde ». Dans ses plus récents travaux, elle a montré que ces cellules peuvent être résistantes aux chimiothérapies et aux immunothérapies et mener à la récidive tumorale.

L’impact:
Tous les tissus de notre corps doivent pouvoir remplacer les cellules mourantes et réparer les plaies localisées. La peau est particulièrement apte à effectuer ces tâches. L’identification et la caractérisation des cellules souches cutanées résidentes qui fabriquent et régénèrent l’épiderme, les glandes sudoripares et les cheveux fournissent des informations importantes sur ce processus de fontaine de jouvence et laissent entrevoir des promesses pour la médecine régénérative et le vieillissement. Dans les tissus normaux, la capacité d’auto-renouvellement des cellules souches et leur prolifération sont contrôlées par des signaux inhibiteurs localisés dans les cellules voisines. Lors d’une blessure, les signaux stimulateurs mobilisent les cellules souches pour qu’elles prolifèrent et guérissent la plaie. Avec le vieillissement, ces signaux d’équilibrage normal basculent vers la quiescence. Dans les troubles inflammatoires, les cellules souches deviennent hyperactives. Dans les cancers, les mécanismes de lutte contre les plaies sont détournés, entraînant une croissance tissulaire incontrôlée. La compréhension des mécanismes de base régissant les cellules souches dans leur tissu indigène fournit de nouvelles stratégies pour la recherche sur les cellules tumorales réfractaires dans le cancer et le rétablissement de la normalité dans les affections inflammatoires.

The Work:
Dr. Nusse’s research has elucidated the mechanism and role of Wnt signaling, one of the most important signaling systems in development. There is now abundant evidence that Wnt signaling is active in cancer and in control of proliferation versus differentiation of adult stem cells, making the Wnt pathway one of the paradigms for the fundamental connections between normal development and cancer.

Among Dr. Nusse’s contributions is the original discovery of the first Wnt gene (together with Harold Varmus) as an oncogene in mouse breast cancer. Afterwards Dr. Nusse identified the Drosophila Wnt homolog as a key developmental gene, Wingless. This led to the general realization of the remarkable links between normal development and cancer, now one of the main themes in cancer research. Using Drosophila genetics, he established the function of beta-catenin as a mediator of Wnt signaling and the Frizzleds as Wnt receptors (with Jeremy Nathans), thereby establishing core elements of what is now called the Wnt pathway. A major later accomplishment of his group was the first successful purification of active Wnt proteins, showing that they are lipid-modified and act as stem cell growth factors.

The Impact:
Wnt signaling is implicated in the growth of human embryos and the maintenance of tissues. Consequently, elucidating the Wnt pathway is leading to deeper insights into degenerative diseases and the development of new therapeutics. The widespread role of Wnt signaling in cancer is significant for the treatment of the disease as well. Isolating active Wnt proteins has led to the use of Wnts by researchers world-wide as stem cell growth factors and the expansion of stem cells into organ-like structures (organoids).

Les travaux:
Le corps animal est composé de nombreuses cellules. Le Dr Takeichi étudiait comment les cellules animales se rassemblent pour former des tissus et des organes, et il a identifié une protéine clé qu’il a appelée « cadhérine ». La cadhérine est présente à la surface d’une cellule et se lie à la même protéine de cadhérine à la surface d’une autre cellule par une interaction similaire, liant ainsi les cellules ensemble. Sans cadhérine, l’adhésion cellule-à-cellule s’affaiblit et conduit à la désorganisation des tissus. Le Dr Takeichi a constaté qu’il existe plusieurs types de cadhérines dans le corps, dont chacun est fabriqué par différents types de cellules, tels que les cellules épithéliales et neuronales. Les cellules ayant les mêmes cadhérines ont tendance à se regrouper, expliquant le mécanisme de la façon dont les différentes cellules sont triées et organisées pour former des organes fonctionnels.

D’autres études menées par le groupe du Dr Takeichi ont montré que la fonction de la cadhérine est soutenue par un certain nombre de protéines cytoplasmiques, y compris les caténines, et leur coopération est essentielle pour la formation des tissus. Ses études ont également révélé que le mécanisme d’adhésion dépendant de la cadhérine est impliqué dans les connexions synaptiques entre les neurones, qui sont importantes pour le câblage cérébral.

L’impact:
La découverte des cadhérines, que l’on retrouve dans toutes les espèces animales multicellulaires, nous a permis d’interpréter comment les systèmes multicellulaires sont générés et régulés. La perte de la fonction de la cadhérine a été mise en cause dans certains cancers, ainsi que dans l’invasivité de nombreux cancers. Des mutations dans des types particuliers de cadhérines entraînent des troubles neurologiques tels que l’épilepsie et la perte auditive. On s’attend à ce que la connaissance de la fonction de la cadhérine contribue au développement de traitements efficaces contre ces maladies.

The Work:
Dr. Kemler, using an immunological approach, developed antibodies directed against surface antigens of early mouse embryos. These antibodies were shown to prevent compaction of the mouse embryo and interfered with subsequent development. Both Dr. Kemler and Dr. Takeichi went on to clone and sequence the gene encoding E-cadherin and demonstrate that it was governing homophilic cell adhesion.

Dr. Kemler also discovered the other proteins that interact with the cadherins, especially the catenins, to generate the machinery involved in animal cell-to-cell adhesion. This provided the first evidence of their importance in normal development and diseases such as cancer. It has been discovered that cadherins and catenins are correlated to the formation and growth of some cancers and how tumors continue to grow. Beta catenin is linked to cell adhesion through interaction with cadherins but is also a key component of the Wnt signalling pathway that is involved in normal development and cancer. There are approximately 100 types of cadherins, known as the cadherin superfamily.

The Impact:
Human tumors are often of epithelial origin. Given the role of E-cadherin for the integrity of an epithelial cell layer, the protein can be considered as a suppressor of tumor growth. The research on the cadherin superfamily has had great impact on fields as diverse as developmental biology, cell biology, oncology, immunology and neuroscience. Mutations in cadherins/catenins are frequently found in tumors. Various screens are being used to identify small molecules that might restore cell adhesion as a potential cancer therapy.

Les travaux:
Les recherches du Dr Nusse ont élucidé le mécanisme et le rôle de la signalisation Wnt, l’un des systèmes de signalisation les plus importants dans le développement. Il existe maintenant des preuves abondantes que la signalisation Wnt est active dans le cancer et dans le contrôle de la prolifération, par opposition à la différenciation, des cellules souches adultes, faisant de la voie Wnt l’un des paradigmes pour les connexions fondamentales entre le développement normal et le cancer.

Parmi les contributions du Dr Nusse, il y a la découverte originale du premier gène Wnt (avec Harold Varmus) comme oncogène dans le cancer du sein de la souris. Par la suite, le Dr Nusse a identifié l’homologue de Drosophila Wnt, Wingless, en tant que gène de développement clé. Cela a mené à la réalisation générale des liens remarquables entre le développement normal et le cancer, qui constituent aujourd’hui l’un des thèmes principaux dans la recherche sur le cancer. En utilisant la génétique de la drosophile, il a établi la fonction de la bêta-caténine en tant que médiateur de la signalisation Wnt, et des Frizzleds en tant que récepteurs Wnt (avec Jeremy Nathans), établissant ainsi les éléments de base de ce qui est maintenant appelé la voie Wnt. Une réalisation majeure ultérieure de son groupe a été la première purification réussie de protéines Wnt actives, montrant qu’elles sont modifiées en lipides et agissent comme facteurs de croissance des cellules souches.

L’impact:
La signalisation Wnt est impliquée dans la croissance des embryons humains et le maintien des tissus. Par conséquent, l’élucidation de la voie Wnt conduit à des analyses plus approfondies sur les maladies dégénératives et le développement de nouvelles thérapies. Le rôle étendu de la signalisation Wnt dans le cancer est également significatif pour le traitement de la maladie. L’isolement de protéines Wnt actives a conduit à leur utilisation par des chercheurs du monde entier comme facteurs de croissance des cellules souches et à l’expansion de cellules souches dans des structures de type organique (organoïdes).

The Work:
UNAIDS estimates that 37 million people were living with HIV and 1.8 million people acquired HIV in 2017. In Africa, which has over two thirds of all people with HIV, adolescent girls and young women have the highest rates of new HIV infections. ABC (Abstinence, Be faithful, and use Condoms) prevention messages have had little impact - due to gender power imbalances, young women are often unable to successfully negotiate condom use, insist on mutual monogamy, or convince their male partners to have an HIV test.

In responding to this crisis, Salim and Quarraisha Abdool Karim started investigating new HIV prevention technologies for women about 30 years ago. After two unsuccessful decades, their perseverance paid off when they provided proof-of-concept that antiretrovirals prevent sexually acquired HIV infection in women. Their ground-breaking CAPRISA 004 trial showed that tenofovir gel prevents both HIV infection and genital herpes. The finding was ranked in the “Top 10 Scientific Breakthroughs of 2010” by the journal, Science. The finding was heralded by UNAIDS and the World Health Organization (WHO) as one of the most significant scientific breakthroughs in AIDS and provided the first evidence for what is today known as HIV pre-exposure prophylaxis (PrEP).

The Abdool Karims have also elucidated the evolving nature of the HIV epidemic in Africa, characterising the key social, behavioural and biological risk factors responsible for the disproportionately high HIV burden in young women. Their identification of the “Cycle of HIV Transmission”, where teenage girls acquire HIV from men about 10 years older on average, has shaped UNAIDS policies on HIV prevention in Africa.

The impact:
CAPRISA 004 and several clinical trials of oral tenofovir led to the WHO recommending a daily tenofovir-containing pill for PrEP as a standard HIV prevention tool for all those at high risk a few years later. Several African countries are among the 68 countries across all continents that are currently making PrEP available for HIV prevention. The research undertaken in Africa by this South African couple has played a key role in shaping the local and global response to the HIV epidemic.

The Work:
UNAIDS estimates that 37 million people were living with HIV and 1.8 million people acquired HIV in 2017. In Africa, which has over two thirds of all people with HIV, adolescent girls and young women have the highest rates of new HIV infections. ABC (Abstinence, Be faithful, and use Condoms) prevention messages have had little impact - due to gender power imbalances, young women are often unable to successfully negotiate condom use, insist on mutual monogamy, or convince their male partners to have an HIV test.

In responding to this crisis, Salim and Quarraisha Abdool Karim started investigating new HIV prevention technologies for women about 30 years ago. After two unsuccessful decades, their perseverance paid off when they provided proof-of-concept that antiretrovirals prevent sexually acquired HIV infection in women. Their ground-breaking CAPRISA 004 trial showed that tenofovir gel prevents both HIV infection and genital herpes. The finding was ranked in the “Top 10 Scientific Breakthroughs of 2010” by the journal, Science. The finding was heralded by UNAIDS and the World Health Organization (WHO) as one of the most significant scientific breakthroughs in AIDS and provided the first evidence for what is today known as HIV pre-exposure prophylaxis (PrEP).

The Abdool Karims have also elucidated the evolving nature of the HIV epidemic in Africa, characterising the key social, behavioural and biological risk factors responsible for the disproportionately high HIV burden in young women. Their identification of the “Cycle of HIV Transmission”, where teenage girls acquire HIV from men about 10 years older on average, has shaped UNAIDS policies on HIV prevention in Africa.

The impact:
CAPRISA 004 and several clinical trials of oral tenofovir led to the WHO recommending a daily tenofovir-containing pill for PrEP as a standard HIV prevention tool for all those at high risk a few years later. Several African countries are among the 68 countries across all continents that are currently making PrEP available for HIV prevention. The research undertaken in Africa by this South African couple has played a key role in shaping the local and global response to the HIV epidemic.

Les travaux:
Le Dr Rouleau a identifié plus de 20 facteurs de risque génétiques prédisposant à une gamme de troubles cérébraux, neurologiques et psychiatriques qui impliquent soit des processus neuro-développementaux soit des événements dégénératifs. Il a défini un nouveau mécanisme pathologique pour des maladies liées à des expansions répétées qui interviennent dans certaines des affections neurodégénératives les plus graves. Il a fait une contribution importante à la compréhension du rôle de variantes de novo dans l’autisme et la schizophrénie. En outre, il a réalisé des progrès importants pour diverses neuropathies, en particulier la sclérose latérale amyotrophique (SLA), où il a participé à l’identification des facteurs de risque génétiques les plus répandus – qui sont maintenant au cœur d’innombrables études sur la SLA à travers le monde.

Le Dr Rouleau a également joué un rôle de pionnier dans la pratique de la science ouverte (SO), transformant l’Institut et hôpital neurologiques de Montréal (le Neuro) pour en faire le premier établissement de SO dans le monde. Le Neuro applique aujourd’hui les principes de la SO pour transformer la recherche et les soins, et accélérer le développement de nouveaux traitements pour les patients grâce au libre accès, aux données ouvertes, aux bio-banques ouvertes, à l’accès libre à la phase initiale de découverte de nouveaux médicaments, et à l’accès à la propriété intellectuelle sans restriction.

L’impact:
L’identification des facteurs de risque génétiques a un certain nombre de conséquences importantes. Premièrement, elle permet un counseling génétique plus précis, ce qui réduit le fardeau de la maladie pour les personnes, les proches et la société touchés. Un cas révélateur est le syndrome d’Andermann, une maladie neuro-développementale et neurodégénérative grave, autrefois relativement commune dans la région du Saguenay-Lac St-Jean, au Québec. Aujourd’hui, cette maladie a presque disparu de cette population. Deuxièmement, l’identification du gène en cause permet la mise au point de traitements. À titre d’exemple, les travaux antérieurs du Dr Rouleau sur une forme de SLA liée au gène superoxyde dismutase-1 (SOD1) ont ouvert la voie à des études qui en sont maintenant aux essais cliniques de phase 2 et laissent entrevoir de grandes promesses.

En servant de laboratoire vivant au cours des deux dernières années, le Neuro a fait office de précurseur dans la façon de mettre en pratique la science ouverte. Comme la SO est une entreprise collective, le Neuro a également engagé un dialogue avec divers intervenants au Canada dans le but de formaliser une alliance nationale de SO dans le domaine des neurosciences. Le travail du Dr Rouleau en SO contribue énormément à la transformation de l’écosystème de la science en stimulant une nouvelle réflexion et en favorisant les communautés de partage. Inspirée par la vision du Neuro, la communauté scientifique mondiale réfléchit aux conventions de recherche actuelles et aux projets collaboratifs, et le mouvement en faveur de la SO prend pied dans des organisations et des établissements aux quatre coins de la planète.

Les travaux:
À l’aide d’une approche immunologique, le Dr Kemler a développé des anticorps dirigés contre des antigènes de surface des premiers embryons de souris. Il a été démontré que ces anticorps empêchent le compactage de l’embryon de souris et interféraient avec le développement ultérieur. Le Dr Kemler et le Dr Takeichi ont tous deux cloné et séquencé le gène codant E-cadhérine et ont démontré qu’il régissait l’adhérence cellulaire homophile.

Le Dr Kemler a également découvert les autres protéines qui interagissent avec les cadhérines, en particulier les caténines, pour produire le mécanisme impliqué dans l’adhésion cellule-à-cellule animale. Cela a fourni la première preuve de leur importance dans le développement normal et les maladies telles que le cancer. Il a été découvert que les cadhérines et les caténines sont corrélées à la formation et à la croissance de certains cancers et à la croissance continue des tumeurs. La bêta-caténine est associée à l’adhésion cellulaire par l’interaction avec les cadhérines, mais est également un élément clé de la voie de signalisation Wnt impliquée dans le développement normal et le cancer. Il existe environ 100 types de cadhérines, connues sous le nom de superfamille des cadhérines.

L’impact:
Les tumeurs humaines sont souvent d’origine épithéliale. Étant donné le rôle joué par la E cadhérine pour l’intégrité de la couche de cellules épithéliales, la protéine peut être considérée comme un suppresseur de la croissance tumorale. La recherche sur la superfamille des cadhérines a eu un grand impact sur des domaines aussi divers que la biologie du développement, la biologie cellulaire, l’oncologie, l’immunologie et les neurosciences. Des mutations dans les cadhérines / caténines sont fréquemment observées dans les tumeurs. Diverses méthodes d’analyse sont utilisées pour identifier de petites molécules susceptibles de restaurer l’adhérence cellulaire comme traitement potentiel du cancer.

Les travaux:
L’ONUSIDA estime que 37 millions de personnes vivaient avec le VIH et que 1,8 million de personnes ont contracté le VIH en 2017. En Afrique, où se trouvent plus des deux tiers des personnes vivant avec le VIH, les adolescentes et les jeunes femmes ont les taux les plus élevés de nouvelles infections au VIH. Les messages de prévention ABC (abstinence, soyez fidèle et utilisez des préservatifs) ont eu peu d’impact – en raison de l’inégalité des pouvoirs entre les sexes, les jeunes femmes sont souvent incapables de négocier avec succès l’utilisation du préservatif, d’insister sur la monogamie mutuelle ou de convaincre leurs partenaires masculins de se soumettre à un test de dépistage du VIH.

En réponse à cette crise, Salim et Quarraisha Abdool Karim ont commencé à étudier, il y a une trentaine d’années, les nouvelles technologies de prévention du VIH pour les femmes. Après deux décennies infructueuses, leur persévérance a porté ses fruits lorsqu’ils ont fait la démonstration de principe que les antirétroviraux préviennent l’infection au VIH sexuellement acquise chez les femmes. Leur essai révolutionnaire, CAPRISA 004, a montré que le gel de ténofovir prévient à la fois l’infection par le VIH et l’herpès génital. La découverte a été classée dans le « Top 10 des percées scientifiques de 2010 » par la revue Science. Cette découverte a été présentée par l’ONUSIDA et l’Organisation mondiale de la Santé (OMS) comme l’une des percées scientifiques les plus importantes dans le domaine du sida et a fourni les premières preuves de ce qu’on appelle aujourd’hui la prophylaxie pré-exposition au VIH (PrEP).

Les Abdool Karim ont également élucidé la nature évolutive de l’épidémie de VIH en Afrique, caractérisant les principaux facteurs de risque sociaux, comportementaux et biologiques responsables de la charge disproportionnée du VIH chez les jeunes femmes. Leur identification du « cycle de transmission du VIH », où les adolescentes contractent le VIH au contact d’hommes environ 10 ans plus âgés en moyenne a façonné les politiques de l’ONUSIDA en matière de prévention du VIH en Afrique.

L’impact:
CAPRISA 004 et plusieurs essais cliniques sur le ténofovir oral ont conduit l’OMS à recommander, quelques années plus tard, une pilule quotidienne contenant du ténofovir pour la PPrE comme outil standard de prévention du VIH pour toutes les personnes à haut risque. Plusieurs pays africains font partie des 68 pays sur tous les continents qui offrent actuellement la PPrE comme mesure de prévention du VIH. Les recherches entreprises en Afrique par ce couple sud-africain ont joué un rôle clé dans l’élaboration de la réponse locale et mondiale à l’épidémie de VIH.

Les travaux:
La carrière de la Dre Mina Bissell a été motivée par les défis que posent des paradigmes établis en biologie cellulaire et développementale. Grâce à ses recherches, la Dre Bissell a montré que l’architecture tissulaire joue un rôle dominant dans la détermination du phénotype cellulaire et tissulaire, et elle a proposé le modèle de « réciprocité dynamique » (DR) entre la matrice extracellulaire (ECM) et la chromatine dans le noyau cellulaire. La réciprocité dynamique fait référence à l’interaction bidirectionnelle continue entre les cellules et leur microenvironnement. Elle a démontré que l’ECM pouvait réguler l’expression des gènes, tout comme l’expression des gènes pouvait réguler l’ECM, et que ces deux phénomènes pourraient survenir simultanément dans des tissus normaux ou malades.

Elle a également développé des systèmes de culture 3D pour étudier l’interaction du microenvironnement et de l’organisation et de la croissance des tissus, en utilisant la glande mammaire comme modèle.

L’impact:
Le modèle de réciprocité dynamique de la Dre Bissell a été prouvé et abondamment établi depuis sa formulation il y a trois décennies et ses observations ont imprégné tous les domaines de la biologie cellulaire et du cancer, avec des conséquences importantes pour les thérapies actuelles et futures. Le travail de la Dre Bissell a entraîné un changement de paradigme fondamental et crucial sur le plan translationnel dans notre compréhension des tissus normaux et malins.

Ses découvertes ont eu de profondes répercussions pour le traitement du cancer en démontrant que les cellules tumorales peuvent être influencées par leur environnement et ne sont pas seulement le produit de leurs mutations génétiques. Ainsi, les cellules des glandes mammaires provenant de cultures tissulaires bidimensionnelles perdent rapidement leur identité, mais une fois placées dans des microenvironnements tridimensionnels appropriés, elles retrouvent la forme et la fonction mammaires. Ce travail présage l’effervescence actuelle au sujet de la production d’organoïdes tissulaires 3D et témoigne de l’approche créative et novatrice de la science de la Dre Bissell.

The Work:
Dr. Mina Bissell’s career has been driven by challenging established paradigms in cellular and developmental biology. Through her research, Dr. Bissell showed that tissue architecture plays a dominant role in determining cell and tissue phenotype and proposed the model of ‘dynamic reciprocity’ (DR) between the extracellular matrix (ECM) and chromatin within the cell nucleus. Dynamic reciprocity refers to the ongoing, bidirectional interaction between cells and their microenvironment. She demonstrated that the ECM could regulate gene expression just as gene expression could regulate ECM, and that these two phenomena could occur concurrently in normal or diseased tissue.

She also developed 3D culture systems to study the interaction of the microenvironment and tissue organization and growth, using the mammary gland as a model.

The Impact:
Dr. Bissell’s model of dynamic reciprocity has been proven and thoroughly established since its proposal three decades ago and the implications have permeated every area of cell and cancer biology, with significant implications for current and future therapies. Dr. Bissell’s work has generated a fundamental and translationally crucial paradigm shift in our understanding of both normal and malignant tissues.

Her findings have had profound implications for cancer therapy by demonstrating that tumor cells can be influenced by their environment and are not just the product of their genetic mutations. For example, cells from the mammary glands grown in two-dimensional tissue cultures rapidly lose their identity, but once placed in proper three-dimensional microenvironments, they regain mammary form and function. This work presages the current excitement about generation of 3D tissue organoids and demonstrates Dr. Bissell’s creative and innovative approach to science.

The Work:
The animal body is made up of numerous cells. Dr. Takeichi was investigating how animal cells stick together to form tissues and organs, and identified a key protein which he named ‘cadherin’. Cadherin is present on the surface of a cell and binds to the same cadherin protein on the surface of another cell through like-like interaction, thereby binding the cells together. Without cadherin, cell to cell adhesion becomes weakened and leads to the disorganization of tissues. Dr. Takeichi found that there are multiple kinds of cadherin within the body, each of which are made by different cell types, such as epithelial and neuronal cells. Cells with the same cadherins tend to cluster together, explaining the mechanism of how different cells are sorted out and organized to form functional organs.

Further studies by Dr. Takeichi’s group showed that cadherin function is supported by a number of cytoplasmic proteins, including catenins, and their cooperation is essential for shaping of tissues. His studies also revealed that the cadherin-dependent adhesion mechanism is involved in synaptic connections between neurons, which are important for brain wiring.

The Impact:
The discovery of cadherins, which are found in all multicellular animal species, has allowed us to interpret how multicellular systems are generated and regulated. Loss of cadherin function has been implicated as the cause of certain cancers, as well as in invasiveness of many cancers. Mutations in special types of cadherin result in neurological disorders, such as epilepsy and hearing loss. The knowledge of cadherin function is expected to contribute to the development of effective treatments against such diseases.

The Work:
Dr. Fuchs has used skin to study how the tissues of our body are able to replace dying cells and repair wounds. The skin must replenish itself constantly to protect against dehydration and harmful microbes. In her research, Fuchs showed that this is accomplished by a resident population of adult stem cells that continually generates a shell of indestructible cells that cover our body surface.

In her early research, Fuchs identified the proteins---keratins—that produce the iron framework of the skin’s building blocks, and showed that mutations in keratins are responsible for a group of blistering diseases in humans. In her later work, Fuchs identified the signals that prompt skin stem cells to make tissue and when to stop. In studying these processes, Fuchs learned that cancers hijack the fundamental mechanisms that tissue stem cells use to repair wounds. Her team pursued this parallel and isolated and characterized the malignant stem cells that are responsible for propagating a type of cancer called “squamous cell carcinoma.” In her most recent work, she showed that these cells can be resistant to chemotherapies and immunotherapies and lead to tumor relapse.

The Impact:
All tissues of our body must be able to replace dying cells and repair local wounds. Skin is particularly adept at performing these tasks. The identification and characterization of the resident skin stem cells that make and replenish the epidermis, sweat glands and hair provide important insights into this fountain of youth process and hold promise for regenerative medicine and aging. In normal tissues, the self-renewing ability of stem cells to proliferate is held in check by local inhibitory signals coming from the stem cells’ neighbours. In injury, stimulatory signals mobilize the stem cells to proliferate and repair the wound. In aging, these normal balancing cues are tipped in favour of quiescence. In inflammatory disorders, stem cells become hyperactivated. In cancers, the wound mechanisms to mobilize stem cells are hijacked, leading to uncontrolled tissue growth. Understanding the basic mechanisms controlling stem cells in their native tissue is providing new strategies for searching out refractory tumor cells in cancer and for restoring normalcy in inflammatory conditions.

Les travaux :
Les recherches du Dr Stillman portent sur la façon dont les chromosomes, y compris l’ADN et les protéines associées aux chromosomes, sont dupliqués dans les cellules humaines et dans la levure, assurant ainsi la transmission exacte du matériel génétique d’une génération à l’autre. Les écarts dans ce processus peuvent mener au cancer. Le Dr Stillman est surtout connu pour sa découverte révolutionnaire du complexe de reconnaissance de l'origine (complexe ORC), le complexe protéique initiateur qui est universel chez les eucaryotes. Ses recherches ultérieures ont permis de déterminer comment débutait la réplication chromosomique et comment elle était régulée. Il a également souligné d’autres fonctions des protéines ORC dans les cellules, notamment le contrôle de la transcription des gènes et la duplication des centrosomes, structures qui orchestrent la séparation des chromosomes pendant la mitose. Des mutations dans les complexe ORC ont été associées au syndrome de Meier-Gorlin, une maladie à l’origine des personnes présentant un nanisme extrême.

L’impact :
Chaque fois qu’une cellule se divise, elle doit copier son ADN de manière égale dans deux nouvelles cellules. Si l’ADN de la cellule n’est pas copié précisément avant sa division, de nouvelles cellules se retrouvent sans l’information génétique nécessaire pour empêcher leur division, provoquer la mort cellulaire ou entraîner la division incontrôlée de nombreuses cellules qui formeront une tumeur.

En décrivant la séquence précise des événements impliqués dans la réplication de l’ADN, le Dr Stillman et le Dr Diffley ont fourni des indices clés sur la façon dont notre génome est dupliqué et la façon dont ce processus est coordonné avec plusieurs autres événements cellulaires essentiels, ce qui a des conséquences pour la compréhension de l’instabilité du génome et de l’hétérogénéité de la tumeur dans le cancer.

The Work:
Our very large genomes must be accurately replicated in each cell cycle, no part of the genome should be replicated more than once and replication must be completed before cell division. Using budding yeast as a model organism, Diffley has shown in molecular detail how DNA replication origins are regulated to ensure once per cell cycle replication. His laboratory has reconstituted the entire chromatin replication pathway using purified proteins. This has led to an understanding of how the replicative DNA helicase is loaded at origins, how it is activated, how it nucleates assembly of the replication machinery and how the replication machinery displaces and re-deposits nucleosomes during replication. He has also shown that DNA damage checkpoints regulate DNA replication on damaged DNA templates by inhibiting replication origin firing and promoting replication fork stability.

The Impact:
Each time a cell divides, it must copy its DNA equally into two new cells. If the cell’s DNA is not copied precisely before it divides, new cells end up without necessary genetic information which can prevent their division, lead to cell death, or cause many cells to divide out of control, forming a tumour.

By describing the exact sequence of events involved in DNA replication, Stillman and Diffley have provided key insights into how our genome is duplicated and how this process is coordinated with many other essential cellular events, which have implications for understanding genome instability and tumour heterogeneity in cancer.

The Work:
Dr. Eaves’ research has focused on leukemia and breast cancer and the normal tissues in which these diseases originate. Eaves together with her husband, Allen Eaves, and a dedicated group of talented trainees developed methodologies to isolate putative stem cells from living mouse and human tissues, and detect them based on their ability to grow as single cells in specialized tissue cultures or in transplanted mice. This made it possible to quantify blood and mammary gland stem cells in different situations, and discover a hidden population of suppressed normal blood stem cells in patients with leukemia, which has stimulated a search for new therapies. Eaves also showed that leukemic stem cells are actually not dividing most of the time. Her studies of breast cells revealed that similar principles apply to understanding the normal growth of this tissue. More recently, she has developed new methods for creating human leukemia and breast cancer experimentally.

Throughout her distinguished career, Dr. Eaves has demonstrated outstanding national and international leadership. She co-founded the Terry Fox Laboratory at the British Columbia Cancer Agency, was a leader in the Canadian Stem Cell Network and held multiple senior roles in the National Cancer Institute of Canada, where she spearheaded the establishment of the Canadian Breast Cancer Research Alliance to create the first national source of breast cancer research funding in Canada.

In addition to the national and international accolades received throughout her career, Dr. Eaves is recognized for her exceptional commitment to the training of more than 100 scientists from around the world, including many now in senior leadership positions. Dr. Eaves is also a passionate advocate for the advancement of women in science, a commitment that led to her recognition as a Status of Women Canada Pioneer.

The Impact:
Dr. Eaves has shown great initiative and immense talent across her five-decade career. Her dedication to multidisciplinary research and to providing the best training possible for aspiring researchers has strengthened Canadian science and garnered international recognition.

Eaves’ scientific findings have been paradigm-shifting, driving the field of stem cell research forward. Her provision of reproducible and rigorously quantitative methods for analysing the rare cells responsible for maintaining normal blood and mammary tissues has enabled many new lines of research. Eaves continues to apply cutting-edge technology and elegant experimental design to the most pertinent problems in stem cell biology and cancer research, constantly contributing to the ongoing pursuit of cures.

Les travaux :
Le Dr Patel a consacré sa carrière de chercheur à accroître la sensibilisation aux problèmes de santé mentale dans le monde grâce à des recherches épidémiologiques démontrant le fardeau des troubles mentaux dans les pays à revenu faible ou intermédiaire, leur lien étroit avec la pauvreté et d’autres priorités de santé publique telles que le VIH et la croissance et le développement de l’enfant, et la recherche axée sur l’intervention dans laquelle il a appliqué une approche systématique à la conception, à la prestation et à l’évaluation d’interventions psychosociales adaptées au contexte prodiguées par des soignants non professionnels au niveau communautaire. Cela englobe les soins primaires pour le traitement de la dépression, de l’anxiété et des troubles liés à la consommation d’alcool, les soins dispensés dans la communauté aux personnes atteintes de schizophrénie et d’autisme, ainsi que la prévention et le traitement des problèmes de santé mentale chez les adolescents par le biais d’interventions en milieu scolaire.

Une grande partie de ses travaux ont été réalisés en partenariat avec Sangath, une ONG indienne qu’il a cofondée en 1996. Sangath est l’un des principaux organismes de recherche en milieu communautaire de l’Inde, et a remporté en 2008 le Prix international de la Fondation MacArthur pour les institutions créatives et efficaces et, en 2016, le Prix de l’OMS du champion de la santé publique en Inde. Le Dr Patel a également cofondé le Centre pour la santé mentale dans le monde et le Réseau d’innovations en santé mentale (à l’École d’hygiène et de médecine tropicale de Londres), ainsi que le Mouvement pour la santé mentale dans le monde, le plus grand réseau mondial de personnes et d’organisations œuvrant à la promotion des services et des droits des personnes vivant avec des troubles de santé mentale. En 2018, il a cofondé l’initiative GlobalMentalHealth@Harvard, qui développe une série d’initiatives innovantes et interdisciplinaires visant à générer et à appliquer des connaissances pour transformer la santé mentale à l’échelle mondiale.

L’impact :
Il y a à peine 10 ans, il était difficile de même imaginer que les problèmes de santé mentale puissent être considérés comme une priorité en santé mondiale. Aujourd’hui, la situation est radicalement différente et un large éventail d’acteurs, appuyés par des ressources, accordent une attention considérable à la santé mentale, en particulier dans les milieux défavorisés et à faibles ressources. Le travail et le leadership du Dr Patel ont joué un rôle crucial en ce sens. Ses recherches ont remis en question de nombreux mythes entourant les problèmes de santé mentale dans un contexte mondial, en démontrant que ces problèmes sont des formes universelles de souffrance humaine, qu’il y a un cercle vicieux de privation et de mauvaise santé mentale, que les problèmes de santé mentale affectent profondément la santé physique et le bien-être des personnes touchées, que des interventions psychosociales peuvent être efficacement prodiguées par des soignants communautaires largement disponibles à un coût abordable, et que les droits fondamentaux des personnes ayant des troubles de santé mentale d’accéder à des soins de qualité et de vivre dans la dignité sont des préoccupations d’envergure mondiale. Son travail et son leadership ont contribué de manière significative à l’émergence du domaine de la santé mentale dans le monde, avec des programmes prioritaires de recherche, d’enseignement, de politiques et de pratiques, par exemple l’initiative de recherche Grands Défis en santé mentale dans le monde, le programme phare mhGAP en santé mentale de l’Organisation mondiale de la Santé, et la première politique nationale de santé mentale de l’Inde.

Les travaux :
Nos très grands génomes doivent être répliqués avec précision dans chaque cycle cellulaire, aucune partie du génome ne doit être répliquée plus d’une fois et la réplication doit être terminée avant la division cellulaire. Utilisant la levure bourgeonnante comme organisme modèle, le Dr Diffley a montré au niveau de détail moléculaire comment les origines de réplication de l’ADN sont régulées pour assurer une réplication unique par cycle cellulaire. Son laboratoire a reconstitué intégralement le cheminement de réplication de la chromatine à l’aide de protéines purifiées. Cela a permis de comprendre comment l’ADN hélicase réplicatif est chargé à l’origine, comment il est activé, comment il amorce l’assemblage du mécanisme de réplication et comment le mécanisme de réplication déplace et redépose les nucléosomes pendant la réplication. Il a également montré que les points de contrôle des dommages à l’ADN régulent la réplication de l’ADN sur des matrices d’ADN endommagées en inhibant le déclenchement de l’origine de la réplication et en favorisant la stabilité de la fourche de réplication.

L’impact :
Chaque fois qu’une cellule se divise, elle doit copier son ADN de manière égale dans deux nouvelles cellules. Si l’ADN de la cellule n’est pas copié précisément avant sa division, de nouvelles cellules se retrouvent sans l’information génétique nécessaire pour empêcher leur division, provoquer la mort cellulaire ou entraîner la division incontrôlée de nombreuses cellules qui formeront une tumeur.

En décrivant la séquence précise des événements impliqués dans la réplication de l’ADN, le Dr Stillman et le Dr Diffley ont fourni des indices clés sur la façon dont notre génome est dupliqué et la façon dont ce processus est coordonné avec plusieurs autres événements cellulaires essentiels, ce qui a des conséquences pour la compréhension de l’instabilité du génome et de l’hétérogénéité de la tumeur dans le cancer.

The Work:
Vale’s research has focused on molecular motor proteins, nature’s nano-scale machines that convert chemical energy into directed movement. Vale began by asking how materials are transported in neurons, which are highly elongated cells that extend up to a meter in humans. Using squid as a model system, he developed a test-tube system to study this cellular transport process. This work led to the discovery of a new motility-producing molecule, which was named “kinesin”. Vale’s laboratory then uncovered the molecular choreography that enables this 1/millionth of an inch machine to drive movement. Collectively, Vale’s work has informed, at a broad level, how living organisms generate motion.

The Impact:
Dr. Vale’s discovery of kinesin and molecular motors transformed the field of cell biology, placing a spotlight on the study of motor proteins. His research has illuminated the fundamental principles that underlie biological motility, an essential attribute of living organisms. The discovery of kinesin led to new tools for studying protein machines more broadly, sparked studies that connected motor proteins to innumerable cellular processes, and contributed to the realization that motility defects underlie various diseases of the nervous system, heart, and other organ systems.

The Work:
Dr. Stillman’s research focuses on how chromosomes, including both DNA and chromosome-associated proteins, are duplicated in human cells and in yeast, thereby ensuring accurate inheritance of genetic material from one generation to the next. Missteps in the process can lead to cancer. Dr. Stillman is most widely known for his groundbreaking discovery of the Origin Recognition Complex (ORC), the initiator protein complex that is universal among eukaryotes. His subsequent research determined how the initiation of chromosome replication occurs and how it is regulated. He also highlighted other functions of ORC proteins in cells, including controlling gene transcription and the duplication of centrosomes, structures that orchestrate chromosome separation during mitosis. Mutations in ORC have been linked to Meier–Gorlin syndrome, a condition that results in people with extreme dwarfism.

The Impact:
Each time a cell divides, it must copy its DNA equally into two new cells. If the cell’s DNA is not copied precisely before it divides, new cells end up without necessary genetic information which can prevent their division, lead to cell death, or cause many cells to divide out of control, forming a tumour.

By describing the exact sequence of events involved in DNA replication, Stillman and Diffley have provided key insights into how our genome is duplicated and how this process is coordinated with many other essential cellular events, which have implications for understanding genome instability and tumour heterogeneity in cancer.

The Work:
Dr. Timothy Springer’s work has changed understanding of cell-to-cell interactions that control immune responses and the movement of leukocyte subsets out of the vasculature into tissues. He discovered the first examples of cell recognition receptors and counter-receptors and the first family of integrins. He subsequently showed molecularly how integrins transmit signals between the exterior and interior of cells and enable cell movement. He opened the way for the first therapeutic use of antibodies to cell-cell recognition receptors to treat autoimmune diseases.

The Impact:
Dr. Springer’s discoveries and world-renowned work have transformed the fields of cell biology and immunology. His discoveries and entrepreneurship have led to an important new class of therapeutics for multiple autoimmune diseases including Psoriasis, Multiple Sclerosis, Ulcerative Colitis, Crohn’s Disease and cancer.

Les travaux :
Les recherches du Dr Vale ont ciblé les protéines motrices moléculaires – les nano-machines naturelles qui convertissent l’énergie chimique en mouvement dirigé. Le Dr Vale s’est d’abord demandé comment les matières sont transportées dans les neurones, des cellules très allongées pouvant atteindre un mètre chez l’humain. Utilisant le calmar comme modèle, il a développé un système pour étudier ce processus de transport cellulaire en éprouvettes. Ces travaux ont conduit à la découverte d’une nouvelle molécule productrice de motilité appelée « kinésine ». Le laboratoire du Dr Vale a ensuite précisé la chorégraphie moléculaire qui permet à cette machine d’un millionième de pouce de diriger le mouvement. Collectivement, les travaux du Dr Vale ont permis de comprendre globalement comment les organismes vivants produisent du mouvement.

L’impact :
La découverte de la kinésine et des moteurs moléculaires par le Dr Vale a transformé le domaine de la biologie cellulaire en mettant l’accent sur l’étude des protéines motrices. Ses recherches ont mis en lumière les principes fondamentaux à la base de la motilité biologique, attribut essentiel des organismes vivants. La découverte de la kinésine a conduit à l’élaboration de nouveaux outils pour étudier les machines protéiques au sens large, suscité des études reliant les protéines motrices à d’innombrables processus cellulaires et contribué à établir que les troubles de motilité sont à l’origine de diverses maladies du système nerveux, du cœur et d’autres systèmes organiques.

The Work:
Dr. Patel has dedicated his research career to raising the global profile of mental health problems through: epidemiological research demonstrating the burden of mental disorders in low- and middle-income countries, their strong association with poverty and with other public health priorities, such as HIV and child growth and development; and intervention research in which he has applied a systematic approach to the design, delivery and evaluation of contextually appropriate psychosocial interventions provided by lay and community health providers. This has included the primary care treatment of depression, anxiety and alcohol use disorders, the community-based care of people with schizophrenia and autism, and the prevention and treatment of adolescent mental health problems through school-based interventions.

Much of his work has been done in partnership with Sangath, an Indian NGO he co-founded in 1996. Sangath is one of India’s leading community-based research organizations which won the MacArthur Foundation International Prize for Creative & Effective Institutions in 2008 and the WHO Public Health Champion of India prize in 2016. Dr. Patel also co-founded the Centre for Global Mental Health and the Mental Health Innovations Network (at the London School of Hygiene & Tropical Medicine) and the Movement for Global Mental Health, the largest global network of individuals and organizations advocating for promoting services and human rights for people living with mental health problems. In 2018, he co-founded the GlobalMentalHealth@Harvard initiative which is developing a suite of innovative, inter-disciplinary, initiatives aimed at implementing and generating knowledge to transform mental health globally.

The Impact:
As recently as 10 years ago, it was difficult to even imagine mental health problems being considered as a global health priority; today, the situation is radically different with considerable attention from a diverse range of global health stakeholders, backed by resources, being focused on mental health, particularly in disadvantaged and low resourced contexts. Patel’s work and leadership has played a critical role in making this happen. His research has challenged many of the myths surrounding mental health problems in the global context, demonstrating that these problems are universal forms of human suffering; that there is a vicious cycle of deprivation and poor mental health; that mental health problems profoundly affect the physical health and well-being of affected persons; that psychosocial interventions can be effectively delivered by widely available and affordable community based providers; and that the human rights of people with mental health problems to access quality care and to a life with dignity are global concerns. This work and his leadership has made significant contributions to the establishment of the field of global mental health, with priority research, teaching, policy and practice agendas, for example the Grand Challenges in Global Mental Health research initiative, the World Health Organization’s flagship mhGAP program on mental health and India’s first national mental health policy.

Les travaux :
Les travaux du Dr Timothy Springer ont changé la compréhension des interactions entre cellules qui contrôlent les réponses immunitaires et le mouvement des sous-ensembles de leucocytes du système vasculaire dans les tissus. Il a découvert les premiers exemples de récepteurs et de contre-récepteurs de reconnaissance cellulaire et la première famille d’intégrines. Il a ensuite montré au niveau moléculaire comment les intégrines transmettent des signaux entre l’extérieur et l’intérieur des cellules et permettent le mouvement cellulaire. Il a ouvert la voie à la première utilisation thérapeutique d’anticorps dirigés contre des récepteurs de reconnaissance cellulaire pour le traitement des maladies auto-immunes.

L’impact :
Les découvertes du Dr Springer et ses travaux de renommée mondiale ont transformé les domaines de la biologie cellulaire et de l’immunologie. Ses découvertes et son esprit d’entreprise ont mené à l’émergence d’une nouvelle classe importante de médicaments pour traiter de multiples maladies auto-immunes, dont le psoriasis, la sclérose en plaques, la colite ulcéreuse, la maladie de Crohn et le cancer.

Les travaux :
La Dre Susan Band Horwitz est surtout connue pour avoir élucidé le mécanisme d’action du Taxol®, un produit naturel tiré d’un arbre, l’if (Taxus brevifolia). La Dre Horwitz a découvert que le Taxol® se liait aux microtubules des cellules, les stabilisant et provoquant l’arrêt du cycle cellulaire et la mort des cellules tumorales. Ces travaux ont permis le passage réussi du Taxol® au stade clinique. C’est l’un des médicaments les plus prescrits dans le monde pour le traitement des cancers de l’ovaire, du sein et du poumon.

L’impact :
Les recherches de la Dre Horwitz ont joué un rôle déterminant en favorisant le développement du Taxol® en vue de leur utilisation en clinique. Alors que personne ne s’intéressait au Taxol® quand elle a entrepris son étude, celui-ci est aujourd’hui un important médicament antitumoral approuvé par la FDA pour le traitement des carcinomes de l’ovaire, du sein et du poumon, ainsi que du sarcome de Kaposi. Le médicament a été administré à des millions de patients atteints du cancer à travers le monde. Le Taxol® est aussi employé dans la préparation des endoprothèses servant au traitement des affections cardiaques. En outre, le Taxol® s’est avéré un outil indispensable pour les scientifiques intéressés par la structure, la dynamique et la fonction des microtubules.

Les travaux :
Les recherches de la Dre Eaves se sont concentrées sur la leucémie et le cancer du sein et sur les tissus normaux où prennent naissance ces maladies. La Dre Eaves, en collaboration avec son mari, Allen Eaves, et un groupe dévoué de stagiaires ont élaboré des méthodologies pour isoler les cellules souches putatives provenant d’humains et de souris vivantes et les détecter en fonction de leur capacité à croître en cellules individuelles dans des cultures tissulaires spécialisées ou des souris greffées. Cela a permis de quantifier les cellules souches du sang et des glandes mammaires dans différentes situations et de découvrir une population cachée de cellules souches sanguines réprimées chez des patients leucémiques, ce qui a stimulé la recherche de nouveaux traitements. La Dre Eaves a également montré que les cellules souches leucémiques ne se divisent pas la plupart du temps. Ses études sur les cellules mammaires ont révélé que des principes similaires s’appliquent à la compréhension de la croissance normale de ce tissu. Plus récemment, elle a mis au point de nouvelles méthodes de création expérimentale de leucémie humaine et de cancer du sein.

Au cours de sa remarquable carrière, la Dre Eaves a démontré un leadership national et international hors du commun. Elle a cofondé le Laboratoire Terry Fox de la British Columbia Cancer Agency, a été l’une des chefs de file du Réseau canadien de cellules souches et a occupé plusieurs postes de direction à l’Institut national du cancer du Canada, où elle a piloté la création de l’Alliance canadienne pour la recherche sur le cancer du sein afin de mettre sur pied la première source nationale de financement de la recherche sur le cancer du sein au Canada.

Outre les éloges nationaux et internationaux qu’elle a récoltés tout au long de sa carrière, la Dre Eaves est reconnue pour son engagement exceptionnel dans la formation de plus d’une centaine de scientifiques de partout dans le monde, dont plusieurs occupent aujourd’hui des postes de direction. La Dre Eaves est également une ardente défenseure de l’avancement des femmes en sciences, un engagement qui l’a menée à devenir une pionnière de Condition féminine Canada.

L’impact :
La Dre Eaves a démontré une grande initiative et un talent immense au cours d’une carrière s’étendant sur cinq décennies. Son dévouement envers la recherche multidisciplinaire et la prestation de la meilleure formation possible aux futurs chercheurs a renforcé la science canadienne et lui a acquis une reconnaissance internationale.

Les découvertes scientifiques de la Dre Eaves ont entraîné un changement de paradigme qui a fait progresser la recherche sur les cellules souches. Les méthodes reproductibles et rigoureusement quantitatives qu’elle a élaborées pour analyser les cellules rares responsables du maintien de tissus mammaires et de sang normaux ont ouvert la voie à plusieurs nouvelles pistes de recherche. La Dre Eaves continue à appliquer des technologies de pointe et une modélisation expérimentale élégante aux problèmes les plus pertinents de la biologie des cellules souches et de la recherche sur le cancer, contribuant constamment à la recherche courante sur les traitements.

The Work:
Dr. Susan Band Horwitz is best known for elucidating the mechanism of action of Taxol®, a natural product obtained from the yew tree, Taxus brevifolia. Horwitz discovered that Taxol® binds to microtubules in cells, stabilizing them, thereby leading to cell cycle arrest and subsequent tumor cell death. This body of work enabled the successful translation of Taxol® into the clinic. It is one of the most frequently prescribed drugs in the world for the treatment of ovarian, breast and lung cancer.

The Impact:
Dr. Horwitz' research played a crucial role in encouraging the development of Taxol® for use in the clinic. Although no one was interested in Taxol® when she began her studies, today it is an important antitumor drug approved by the FDA for the treatment of ovarian, breast and lung carcinomas, as well as Kaposi’s Sarcoma. The drug has been given to millions of cancer patients worldwide. Taxol® also is used in the preparation of stents for cardiac disease. In addition, Taxol® has proven to be an indispensable tool for scientists interested in microtubule structure, dynamics, and function.

Bio
Susan Band Horwitz, Ph.D., was born in Winthrop, Massachusetts, a small town near Boston, where she attended public high school. She enrolled at Bryn Mawr College with the intent to major in history, but after taking a required course in science, she switched her major to biology. She received her Ph.D. in Biochemistry from Brandeis University, where her mentor was Professor Nathan O. Kaplan, with whom she studied enzyme kinetics. She was a postdoctoral fellow in the Departments of Pharmacology at Tufts University Medical School, Emory University Medical School and Albert Einstein College of Medicine. In 1970, she joined the faculty at Einstein, where she is a Distinguished Professor and holds the Falkenstein Chair in Cancer Research in the Department of Molecular Pharmacology.

Dr. Horwitz has received numerous honors and awards, including the C. Chester Stock Award from Memorial Sloan Kettering Cancer Center, the Warren Alpert Foundation Prize from Harvard Medical School, The Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research, The American Cancer Society's Medal of Honor and the AACR Lifetime Achievement Award in Cancer Research. Dr. Horwitz served as president of the American Association of Cancer Research. She is a member of the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences, the American Philosophical Society and is also a fellow of the New York Academy of Medicine and the American Pharmacognosy Society.

†1921-2007

Seymour Benzer also received the Canada Gairdner International Award in 1964 in recognition of his outstanding contributions to the knowledge of genetics and molecular biology, and in particular for his elucidation of the fine structure of genes, which has made it possible to extend the limits of genetic resolution by relating genetic changes to chemical alterations in deoxyribonucleic acid, thus clarifying the chemical bases of heredity in determining the nature and properties of cells and viruses.

† 1918-2013

Frederick Sanger also received the Canada Gairdner International Award in 1979 in recognition of his development of methods for the sequencing of DNA and of his contributions to new concepts of gene structure.

Les travaux :

Ensemble, les travaux du Dr Solter et du Dr Surani ont contribué à la compréhension des conséquences de l’empreinte génomique sur le développement et les mécanismes moléculaires. En 1984, ils ont publié des études parallèles faisant la démonstration du concept de l’empreinte génomique. Toutes les cellules de l’animal renferment deux copies de chaque gène autosomique, l’une de la mère et l’autre du père, et dans la plupart des cas les deux copies sont exprimées. Cependant, les gènes « empreints » ne sont exprimés qu’à partir de la copie héritée de la mère ou du père. L’empreinte génomique joue un rôle important chez les mammifères, affectant le développement embryonnaire et placentaire et la transmission des nutriments au fœtus, et régulant les aspects critiques de la physiologie des mammifères, tels que le métabolisme, le développement neuronal et le comportement adulte. Des recherches approfondies basées sur cette découverte ont conduit à l’identification de nombreux gènes empreints dont les allèles sont exprimés différemment en fonction du parent d’origine.

L’impact :

Les empreintes défectueuses peuvent entraîner des anomalies du développement, physiologiques et comportementales chez les souris, et entraîner des maladies chez les humains. Il y a de plus en plus de preuves de l’importance de l’empreinte dans la susceptibilité à la maladie liée à des syndromes développementaux comme ceux de Beckwith-Wiedemann, Angelman et Prader-Willi, à une variété de cancers et de troubles neurologiques et à l’obésité. Elle a également des effets sur divers aspects du développement et de la physiologie des mammifères, tels que les cellules souches, la température corporelle, la nutrition et le comportement. Leurs travaux sont à l’origine de l’une des principales découvertes qui ont ouvert le champ de l’épigénétique, l’étude des changements héréditaires dans la fonction des gènes sans changements dans la séquence d’ADN.

Les travaux :

Ensemble, les travaux du Dr Solter et du Dr Surani ont contribué à la compréhension des conséquences de l’empreinte génomique sur le développement et les mécanismes moléculaires. En 1984, ils ont publié des études parallèles faisant la démonstration du concept de l’empreinte génomique. Toutes les cellules de l’animal renferment deux copies de chaque gène autosomique, l’une de la mère et l’autre du père, et dans la plupart des cas les deux copies sont exprimées. Cependant, les gènes « empreints » ne sont exprimés qu’à partir de la copie héritée de la mère ou du père. L’empreinte génomique joue un rôle important chez les mammifères, affectant le développement embryonnaire et placentaire et la transmission des nutriments au fœtus, et régulant les aspects critiques de la physiologie des mammifères, tels que le métabolisme, le développement neuronal et le comportement adulte. Des recherches approfondies basées sur cette découverte ont conduit à l’identification de nombreux gènes empreints dont les allèles sont exprimés différemment en fonction du parent d’origine.

L’impact :

Les empreintes défectueuses peuvent entraîner des anomalies du développement, physiologiques et comportementales chez les souris, et entraîner des maladies chez les humains. Il y a de plus en plus de preuves de l’importance de l’empreinte dans la susceptibilité à la maladie liée à des syndromes développementaux comme ceux de Beckwith-Wiedemann, Angelman et Prader-Willi, à une variété de cancers et de troubles neurologiques et à l’obésité. Elle a également des effets sur divers aspects du développement et de la physiologie des mammifères, tels que les cellules souches, la température corporelle, la nutrition et le comportement. Leurs travaux sont à l’origine de l’une des principales découvertes qui ont ouvert le champ de l’épigénétique, l’étude des changements héréditaires dans la fonction des gènes sans changements dans la séquence d’ADN.

Les travaux :

Le principal domaine de recherche de la Dre Shepherd est celui des essais cliniques sur le cancer du poumon. Elle a joué un rôle déterminant dans le développement et l’évaluation de nouvelles modalités de traitement des patients atteints d’un cancer du poumon à petites cellules ou non à petites cellules aux niveaux local, national et international. Sous sa direction, le site de recherche sur le cancer du poumon du Groupe des essais cliniques canadiens a mené de nombreuses études internationales axées sur les changements de pratiques. Ces études marquantes ont montré que la chimiothérapie post-opératoire peut modifier le taux de guérison du cancer du poumon réséqué et que les traitements ciblés au niveau moléculaire peuvent améliorer la survie même aux stades les plus avancés de la maladie. En collaboration avec ses collègues des sciences fondamentales, elle a établi des banques de tumeurs du cancer du poumon qui se sont révélées être une ressource inestimable pour étudier la biologie du cancer du poumon au niveau moléculaire et faire le pont entre le laboratoire et la clinique.

L’impact :

Au cours des trois dernières décennies, la Dre Shepherd a conçu et dirigé des essais cliniques qui ont révolutionné le traitement et les résultats chez les patients atteints d’un cancer du poumon à l’échelle mondiale. Elle a encadré plus de 40 chercheurs postdoctoraux dans le monde entier, dont plusieurs occupent aujourd’hui des postes universitaires de haut rang dans leur pays d’origine. Elle est l’auteure ou la coauteure de plus de 500 publications évaluées par des pairs et de 35 chapitres d’ouvrages.

Les travaux :

Les recherches du Dr Hegemann se sont concentrées presque entièrement sur la caractérisation des photorécepteurs sensoriels naturels, principalement à partir de microalgues. Le Dr Hegemann a caractérisé les réponses comportementales et photoélectriques de l’algue unicellulaire, Chlamydomonas, ce qui a mené à l’hypothèse que les photorécepteurs à l’origine de ces réponses étaient une rhodopsine qui unifiait le capteur et le canal ionique dans une protéine. Il a éventuellement vérifié cette hypothèse en identifiant le canal photosensible, la channelrhodopsine, et en démontrant sa fonctionnalité dans les cellules animales.

D’importance égale, son groupe a découvert les principes fondamentaux des protéines channelrhodopsines uniques au niveau moléculaire détaillé à l’aide d’un large éventail de techniques génomiques, biophysiques, électrophysiologiques et structurelles, avec de nombreux mutants, en étroite collaboration avec le Dr Karl Deisseroth. Cela leur a permis de déchiffrer le mécanisme inédit de canal ionique photosensible, y compris ses pores contrôlés par photons et sa sélectivité ionique. Ce travail pionnier a fondamentalement ouvert la voie à l’optogénétique (la technologie par laquelle des protéines activées par la lumière – au premier rang la channelrhodopsine – permettent de contrôler des cellules sélectionnées dans des systèmes aussi complexes que le cerveau mammalien, avec une précision spatiale et temporelle inégalée, par émission lumineuse.

L’impact :

L’optogénétique a été utilisée avec succès pour améliorer notre compréhension de la fonction du circuit neuronal médiateur du comportement normal et de la dysfonction sous-jacente des troubles neurologiques et psychiatriques. L’optogénétique est une technologie qui a révolutionné le domaine des neurosciences et permis une nouvelle génération d’expériences qui sondent le rôle causal de composants de circuits neuronaux spécifiques.

Les travaux :

La recherche du Dr Boyden s’est concentrée sur les technologies optiques permettant de comprendre comment les neurones travaillent ensemble pour produire un comportement et comment leur activité change dans les états pathologiques ou peut être modifiée pour traiter ceux-ci. En collaboration avec son collègue lauréat, le Dr Karl Deisseroth, le Dr Boyden a réfléchi à la façon dont les opsines microbiennes pourraient être utilisées pour exercer un contrôle optique de l’activité neurale alors que les deux étaient encore étudiants en 2000. Ensemble, ils ont travaillé à faire la démonstration du premier contrôle optique de l’activité neurale en utilisant des opsines microbiennes à l’été 2004; le Dr Deisseroth et le Dr Boyden ont effectué, respectivement, le travail de transfection génique et de stimulation optique. Au M.I.T., l’équipe du Dr Boyden a réalisé le premier silençage optogénétique (2007), le premier silençage optogénétique efficace chez des mammifères vivants (2010), le silençage optogénétique non invasif (2014), le contrôle optogénétique multicolore (2014) et le contrôle optogénétique monocellulaire temporellement précis (2017).

L’impact :

Les travaux du Dr Boyden ont donné aux neuroscientifiques la capacité d’activer ou de désactiver avec précision des cellules cérébrales pour voir comment elles contribuent aux états pathologiques ou à leur traitement. En contrôlant les cellules cérébrales par optogénétique, il est devenu possible de comprendre comment des modèles spécifiques d’activité cérébrale pourraient être utilisés pour atténuer les convulsions, supprimer les tremblements parkinsoniens, activer le système immunitaire du cerveau pour vaincre la maladie d’Alzheimer, et faire d’autres altérations au cerveau qui sont bénéfiques à la santé.

Les travaux :

Ensemble, les travaux du Dr Solter et du Dr Surani ont contribué à la compréhension des conséquences de l’empreinte génomique sur le développement et les mécanismes moléculaires. En 1984, ils ont publié des études parallèles faisant la démonstration du concept de l’empreinte génomique. Toutes les cellules de l’animal renferment deux copies de chaque gène autosomique, l’une de la mère et l’autre du père, et dans la plupart des cas les deux copies sont exprimées. Cependant, les gènes « empreints » ne sont exprimés qu’à partir de la copie héritée de la mère ou du père. L’empreinte génomique joue un rôle important chez les mammifères, affectant le développement embryonnaire et placentaire et la transmission des nutriments au fœtus, et régulant les aspects critiques de la physiologie des mammifères, tels que le métabolisme, le développement neuronal et le comportement adulte. Des recherches approfondies basées sur cette découverte ont conduit à l’identification de nombreux gènes empreints dont les allèles sont exprimés différemment en fonction du parent d’origine.

L’impact :

Les empreintes défectueuses peuvent entraîner des anomalies du développement, physiologiques et comportementales chez les souris, et entraîner des maladies chez les humains. Il y a de plus en plus de preuves de l’importance de l’empreinte dans la susceptibilité à la maladie liée à des syndromes développementaux comme ceux de Beckwith-Wiedemann, Angelman et Prader-Willi, à une variété de cancers et de troubles neurologiques et à l’obésité. Elle a également des effets sur divers aspects du développement et de la physiologie des mammifères, tels que les cellules souches, la température corporelle, la nutrition et le comportement. Leurs travaux sont à l’origine de l’une des principales découvertes qui ont ouvert le champ de l’épigénétique, l’étude des changements héréditaires dans la fonction des gènes sans changements dans la séquence d’ADN.

Les travaux :

Les Drs Murray et Lopez sont cofondateurs de l’Étude sur le fardeau mondial de la maladie (GBD), un effort scientifique systématique visant à quantifier l’ampleur comparative de la perte de santé due à l’ensemble des maladies, blessures et facteurs de risque importants, selon l’âge, le sexe et la localisation au fil du temps. Leur première collaboration au début des années 1990 leur a permis de produire des estimations pour huit régions, 107 maladies et 10 facteurs de risque. Plus de deux décennies après, l’édition la plus récente de l’étude, maintenant publiée annuellement dans la revue médicale internationale The Lancet, couvre plus de 300 maladies et blessures dans près de 200 pays, selon l’âge et le sexe, de 1990 à aujourd’hui, permettant de faire des comparaisons temporelles entre les groupes d’âge et entre les populations. Environ 3200 collaborateurs établis dans 140 pays contribuent à ce qui a été reconnu comme la plus vaste collaboration éditoriale dans le domaine de la science au monde. Au cours des dernières années, le projet s’est étendu à la quantification des inégalités sociodémographiques en matière de santé et à la mesure de la santé au niveau local en cartographiant les nations par blocs de 5 x 5 kilomètres. L’étude est coordonnée par l’Institute for Health Metrics and Evaluation de l’Université de Washington, où le Dr Murray agit comme directeur.

L’impact :

L’étude GBD a conduit à des changements de politique et à des améliorations des systèmes de santé dans de nombreux pays, dont la Chine, le Royaume-Uni, l’Inde, le Rwanda, la Colombie, l’Arabie saoudite, l’Indonésie et les Philippines. Les National Institutes of Health des États-Unis, l’Organisation mondiale de la Santé, la Banque mondiale et la Fondation Bill & Melinda Gates utilisent les résultats de la GBD pour orienter leurs décisions en matière d’établissement des priorités et de dépenses. L’étude a généré près de 20 000 publications évaluées par des pairs et a reçu plus de 700 000 citations dans des études et des rapports scientifiques.

Les travaux :

Les Drs Murray et Lopez sont cofondateurs de l’Étude sur le fardeau mondial de la maladie (GBD), un effort scientifique systématique visant à quantifier l’ampleur comparative de la perte de santé due à l’ensemble des maladies, blessures et facteurs de risque importants, selon l’âge, le sexe et la localisation au fil du temps. Leur première collaboration au début des années 1990 leur a permis de produire des estimations pour huit régions, 107 maladies et 10 facteurs de risque. Plus de deux décennies après, l’édition la plus récente de l’étude, maintenant publiée annuellement dans la revue médicale internationale The Lancet, couvre plus de 300 maladies et blessures dans près de 200 pays, selon l’âge et le sexe, de 1990 à aujourd’hui, permettant de faire des comparaisons temporelles entre les groupes d’âge et entre les populations. Environ 3200 collaborateurs établis dans 140 pays contribuent à ce qui a été reconnu comme la plus vaste collaboration éditoriale dans le domaine de la science au monde. Au cours des dernières années, le projet s’est étendu à la quantification des inégalités sociodémographiques en matière de santé et à la mesure de la santé au niveau local en cartographiant les nations par blocs de 5 x 5 kilomètres. L’étude est coordonnée par l’Institute for Health Metrics and Evaluation de l’Université de Washington, où le Dr Murray agit comme directeur.

L’impact :

L’étude GBD a conduit à des changements de politique et à des améliorations des systèmes de santé dans de nombreux pays, dont la Chine, le Royaume-Uni, l’Inde, le Rwanda, la Colombie, l’Arabie saoudite, l’Indonésie et les Philippines. Les National Institutes of Health des États-Unis, l’Organisation mondiale de la Santé, la Banque mondiale et la Fondation Bill & Melinda Gates utilisent les résultats de la GBD pour orienter leurs décisions en matière d’établissement des priorités et de dépenses. L’étude a généré près de 20 000 publications évaluées par des pairs et a reçu plus de 700 000 citations dans des études et des rapports scientifiques.

The Work:

A challenge for both basic and clinical neuroscience is the complexity of brain structure and function which makes it difficult to determine how electrical activity within individual cells causes behavior. Deisseroth adapted light-activated proteins from microbes (including the channelrhodopsins) to allow individual types of cells to be controlled with light in real time during behavior. The initial paper from Deisseroth’s lab, along with graduate students Feng Zhang (who received a Canada Gairdner International Award in 2016) and Edward Boyden, identified a key piece of the puzzle: channelrhodopsin-based control of neurons with light. Subsequently Deisseroth’s group designed the necessary tools for targeting opsins and light to circuit elements of interest and applied the final resulting method (optogenetics) to discover principles of brain function in health and disease.

Of equal importance, his group discovered the fundamental principles of the unique channelrhodopsin proteins in molecular detail by a wide range of genomic, biophysical, electrophysiological and structural techniques with many mutants in close collaboration with Peter Hegemann. This led to their deciphering of the unprecedented light-gated ion channel mechanism including its pore gating by photons and its ion selectivity. This basic work also fundamentally enabled optogenetics (the technology wherein light-activated proteins– first and foremost channelrhodopsin- allow control of selected cells within systems as complex as the mammalian brain, with unprecedented precision in space and time by delivery of light).

The Impact:

Optogenetics has been successfully employed to enhance our understanding of neural circuit function mediating normal behavior and dysfunction underlying neurological and psychiatric disorders. Optogenetics is a technology that has revolutionized the field of neuroscience and has enabled a new generation of experiments that probe the causal roles of specific neural circuit components.

The Work:

Dr. Boyden’s research has focused on optical technologies for understanding how neurons work together to generate behavior and how their activity changes in disease states or can be changed to treat such diseases. Boyden, along with fellow laureate Karl Deisseroth, brainstormed about how microbial opsins could be used to mediate optical control of neural activity while both were students in 2000. Together, they collaborated to demonstrate the first optical control of neural activity using microbial opsins in the summer of 2004, with Deisseroth, and Boyden, performing the gene transfection and the optical stimulation respectively. At MIT, Boyden’s team developed the first optogenetic silencing (2007), the first effective optogenetic silencing in live mammals (2010), noninvasive optogenetic silencing (2014), multicolor optogenetic control (2014), and temporally precise single-cell optogenetic control (2017).

The Impact:

Boyden’s work has given neuroscientists the ability to precisely activate or silence brain cells to see how they contribute to pathological states or the remedy thereof. By optogenetically controlling brain cells, it has become possible to understand how specific patterns of brain activity might be used to quiet seizures, cancel out Parkinsonian tremors, activate the brain’s immune system to overcome Alzheimer’s and make other health-promoting alterations to the brain.

The Work:

Dr. Shepherd's major area of research is in the field of clinical trials for lung cancer. She has been instrumental in developing and evaluating new treatment modalities at the local, national and international level for patients with both small cell and non-small cell lung cancer. Under her leadership, the Canadian Clinical Trials Group Lung Cancer Site conducted many international practice-changing studies. These landmark studies have shown that post-operative chemotherapy can change the cure rate for resected lung cancer and that molecularly targeted treatments can improve survival even in the most advanced stages of the disease. In collaboration with her basic science colleagues, she has established lung cancer tumour banks that have proved to be an invaluable resource to study the biology of lung cancer at a molecular level and to link the laboratory to the clinic.

The Impact:

Dr. Shepherd has designed and led paradigm-shifting clinical trials over the past three decades that have changed treatment and outcomes for patients with lung cancer at a global level. She has mentored more than 40 post-doctoral research fellows from around the world, many of whom now hold senior academic positions in their home countries. She has authored or co-authored more than 500 peer-reviewed publications and 35 book chapters.

The Work:

Murray and Lopez are co-founders of the Global Burden of Disease study, a systematic, scientific effort to quantify the comparative magnitude of health loss from all major diseases, injuries, and risk factors by age, sex, and location over time. Their first collaboration in the early 1990s calculated estimates for eight regions, 107 diseases, and 10 risk factors. More than two decades later, the latest edition of the study, now published annually in the international medical journal, The Lancet, covers more than 300 diseases and injuries in nearly 200 countries by age and sex from 1990 to the present, allowing comparisons over time across age groups and among populations. Approximately 3,200 collaborators in 140 nations contribute to what has been recognized as the world’s largest publishing collaboration in science. In recent years, the GBD enterprise has expanded into quantifying sociodemographic inequalities in health and measuring health on the local level by mapping nations in 5x5 kilometer increments. It is coordinated by the Institute for Health Metrics and Evaluation at the University of Washington where Murray serves as Director.

The Impact:

The GBD has led to policy changes and improvements in health systems in numerous countries including China, the United Kingdom, India, Rwanda, Colombia, Saudi Arabia, Indonesia and the Philippines. The U.S. National Institutes of Health, the World Health Organization, the World Bank, and the Bill & Melinda Gates Foundation all use GBD results to guide their priority setting and spending decisions. The study has generated nearly 20,000 peer-reviewed publications and has received more than 700,000 citations in scientific studies and reports.

The Work:

Murray and Lopez are co-founders of the Global Burden of Disease study, a systematic, scientific effort to quantify the comparative magnitude of health loss from all major diseases, injuries, and risk factors by age, sex, and location over time. Their first collaboration in the early 1990s calculated estimates for eight regions, 107 diseases, and 10 risk factors. More than two decades later, the latest edition of the study, now published annually in the international medical journal, The Lancet, covers more than 300 diseases and injuries in nearly 200 countries by age and sex from 1990 to the present, allowing comparisons over time across age groups and among populations. Approximately 3,200 collaborators in 140 nations contribute to what has been recognized as the world’s largest publishing collaboration in science. In recent years, the GBD enterprise has expanded into quantifying sociodemographic inequalities in health and measuring health on the local level by mapping nations in 5x5 kilometer increments. It is coordinated by the Institute for Health Metrics and Evaluation at the University of Washington where Murray serves as Director.

The Impact:

The GBD has led to policy changes and improvements in health systems in numerous countries including China, the United Kingdom, India, Rwanda, Colombia, Saudi Arabia, Indonesia and the Philippines. The U.S. National Institutes of Health, the World Health Organization, the World Bank, and the Bill & Melinda Gates Foundation all use GBD results to guide their priority setting and spending decisions. The study has generated nearly 20,000 peer-reviewed publications and has received more than 700,000 citations in scientific studies and reports.

The Work:

Together, the work of Dr. Solter and Dr. Surani contributed to the understanding of the developmental consequences and molecular mechanisms of genomic imprinting. In 1984, they released parallel studies that demonstrated the concept of genomic imprinting. All cells in the animal contain two copies of every autosomal gene, one from the mother and one from the father, and in most cases both copies are expressed. However, “imprinted” genes are expressed only from either the maternally or the paternally inherited copy. Genomic imprinting has widespread roles in mammals, affecting embryonic and placental development and transmission of nutrients to the fetus, and regulating critical aspects of mammalian physiology, such as metabolism, neuronal development and adult behaviour. Extensive research based on this discovery led to the identification of numerous imprinted genes whose alleles are differentially expressed depending on the parent of origin.

The Impact:

Faulty imprints can lead to developmental, physiological and behavioural anomalies in mice, and result in diseases in humans. There is growing evidence for the importance of imprinting in disease susceptibility from developmental syndromes like Beckwith-Wiedemann, Angelman and Prader-Willi, to a variety of cancers and neurological disorders and obesity. It also has effects on diverse aspects of mammalian development and physiology, such as stem cells, core body temperature, nutrition and behaviour. Their work is one of the key discoveries that started the field of epigenetics, the study of heritable changes in gene function without changes in the DNA sequence.

The Work:

Together, the work of Dr. Solter and Dr. Surani contributed to the understanding of the developmental consequences and molecular mechanisms of genomic imprinting. In 1984, they released parallel studies that demonstrated the concept of genomic imprinting. All cells in the animal contain two copies of every autosomal gene, one from the mother and one from the father, and in most cases both copies are expressed. However, “imprinted” genes are expressed only from either the maternally or the paternally inherited copy. Genomic imprinting has widespread roles in mammals, affecting embryonic and placental development and transmission of nutrients to the fetus, and regulating critical aspects of mammalian physiology, such as metabolism, neuronal development and adult behaviour. Extensive research based on this discovery led to the identification of numerous imprinted genes whose alleles are differentially expressed depending on the parent of origin.

The Impact:

Faulty imprints can lead to developmental, physiological and behavioural anomalies in mice, and result in diseases in humans. There is growing evidence for the importance of imprinting in disease susceptibility from developmental syndromes like Beckwith-Wiedemann, Angelman and Prader-Willi, to a variety of cancers and neurological disorders and obesity. It also has effects on diverse aspects of mammalian development and physiology, such as stem cells, core body temperature, nutrition and behaviour. Their work is one of the key discoveries that started the field of epigenetics, the study of heritable changes in gene function without changes in the DNA sequence.

The Work:

Dr. Hegemann’s research focused almost entirely on the characterization of natural sensory photoreceptors, mainly from microalgae. Hegemann has characterized behavioral and photoelectric responses of the unicellular alga, Chlamydomonas, which cumulated in the claim that the photoreceptors for these responses was a rhodopsin that unified the sensor and ion channel in one protein. He finally proved this hypothesis by identifying the light-gated channel, channelrhodopsin and by demonstrating its functionality in animal cells.

Of equal importance, his group discovered the fundamental principles of the unique channelrhodopsin proteins in molecular detail by a wide range of genomic, biophysical, electrophysiological and structural techniques with many mutants in close collaboration with Karl Deisseroth. This led to their deciphering of the unprecedented light-gated ion channel mechanism, including its pore gating by photons and its ion selectivity. This basic work also fundamentally enabled optogenetics (the technology wherein light-activated proteins– first and foremost channelrhodopsin- allow control of selected cells within systems as complex as the mammalian brain, with unprecedented precision in space and time by delivery of light).

The Impact:

Optogenetics has been successfully employed to enhance our understanding of neural circuit function mediating normal behavior and dysfunction underlying neurological and psychiatric disorders. Optogenetics is a technology that has revolutionized the field of neuroscience and has enabled a new generation of experiments that probe the causal roles of specific neural circuit components.

† 1942-2018

Sir John Sulston's recognition of the value of the nematode worm c. elegans as an experimental organism and his achievement in mapping the developmental lineage of all its 959 somatic cells led to his first Gairdner Award with Sydney Brenner in 1991. He went on to sequence the c. elegans genome in collaboration with Robert Waterston; completed in 1998, this was the first animal genome to be sequenced. He has played a major role in the Human Genome Project, both personally and through the Sanger Centre, which he founded in 1993 for the mapping and sequencing of the human and other genomes and served as Director from 1992-2000.

Dr. Sulston has spent virtually his entire career at the University of Cambridge. He earned a BA in organic chemistry and a PhD, spent three years as a postdoctoral fellow at the Salk Institute and then returned to Cambridge as a member of the Laboratory of Molecular Biology. He has received numerous honors and in 2001 was knighted in the New Year's Honour list.

Sir John Sulston also received the Canada Gairdner International Award in 2002 for major seminal contributions to the sequencing of the human and other genomes.

† 1925-2017

Oliver Smithies also received the Canada Gairdner International Award in 1990 for the discovery, development and application of gel electrophoresis methods that allow the separation and identification of specific proteins and nucleic acids.

As of 2002, Dr. Francis Collins is the current Director of the National Human Genome Research Institute of the National Institutes of Health, USA. In this role he oversees the Human Genome Project, the complex multidisciplinary scientific exercise directed at mapping and sequencing the entire human DNA and determining aspects of its function. An initial analysis of the human genome sequence was published in 2001 and the data has been made available to the scientific community.

Dr. Collins is a graduate of the University of Virginia with a PhD in Physical Chemistry from Yale and an MD from the University of North Carolina. After a fellowship in Human Genetics and Pediatrics at Yale, he joined the University of Michigan, Ann Arbor, where he remained until he was appointed to replace James Watson at NIH in 1993. His research has contributed to the identification of the genes for cystic fibrosis, neurofibromatosis and Huntington disease. His numerous honors include a Gairdner Award in 1990 for his work on cystic fibrosis.

† 1927-2019

Sydney Brenner also received the Canada Gairdner International Award in 1978 in recognition of his highly original and conceptual contributions to molecular biology, and to the understanding of how genetic information is read and translated.

Henry Friesen also received the Canada Gairdner International Award in 1977 in recognition of his contributions to the understanding of the biochemistry, physiology and pathophysiology of lactogenic hormones and, in particular, for the identification of human prolactin.

Les travaux Le Dr Rappuoli est un pionnier dans le domaine des vaccins et a été à l’origine de plusieurs nouveaux concepts scientifiques. Tout d’abord, il a introduit la notion selon laquelle les toxins bactériennes peuvent être détoxifiées par manipulation génétique (détoxification génétique, 1987). Puis, la notion selon laquelle il est préférable d’étudier les microbes dans le milieu cellulaire où elles interagissent (microbiologie cellulaire, 1996), enfin, l’utilisation de génomes pour developer de nouveaux vaccins (vaccinologie inverse, 2000). Dans le processus de vaccinologie inverse, la séquence génomique complète d’un agent pathogène est passée au crible à l’aide d’outils bioinformatiques pour aider à déterminer quels gènes codent pour quelles protéines, contre lesquelles des vaccins peuvent être développés. L’impact Le Dr Rappuoli a également travaillé sur plusieurs molécules qui ont été intégrées à des vaccins homologués. Il a caractérisé la molécule CRM197, aujourd’hui la plus largement utilisée comme vecteur des vaccins contre Haemophilus influenzae, les méningocoques et les pneumocoques. Subséquemment, il a développé un vaccin contre la coqueluche renfermant la toxine génétiquement détoxifiée de la coqueluche, ainsi que le premier vaccin conjugué contre le méningocoque C qui a permis d’éradiquer la maladie au Royaume-Uni en 2000. Son travail sur la vaccinologie inverse a conduit à l’homologation du premier vaccin contre le méningocoque B approuvé en Europe et au Canada en 2013 et aux États-Unis en 2015.

Les travaux Le professeur Kay et ses collègues ont apporté des contributions importantes au domaine de la spectroscopie biomoléculaire à résonance magnétique nucléaire (RMN) avec le développement de méthodes servant à « visualiser » les molécules de protéines dans leur solution ambiante naturelle et de recueillir des renseignements sur la façon dont leurs formes évoluent avec le temps, conduisant à une fonction biologique. Ces méthodes ont fait la lumière sur la façon dont les molécules impliquées dans la neurodégénérescence peuvent former des structures anormales qui aboutissent éventuellement à des états pathologiques. En outre, ces travaux nous ont permis de mieux comprendre comment fonctionnent les machines cellulaires et comment les communications entre les différentes parties de ces machines peuvent servir de cibles pour le développement de médicaments dans la lutte contre certains cancers. L’impact Ces recherches ont approfondi notre compréhension de la nature flexible de la structure des protéines et de l’importance de cette flexibilité à la fois pour la fonction et la dysfonction. Cela a ouvert de nouvelles perspectives sur les régions clés des molécules qui pourraient devenir la cible de médicaments. Les méthodes élaborées par le Dr Kay sont employées dans des laboratoires à travers le monde, notamment ceux qui font des recherches sur des maladies telles que le diabète, le cancer et les maladies cardiovasculaires. Les outils mis au point par son groupe de recherche sont diffusés librement et sont largement utilisés dans le monde entier.

Les travaux : Dans les années 1980, le VIH/sida était largement considéré comme une maladie frappant les homosexuels. Tout au long des années 1980, le Dr Frank Plummer a mené des recherches, facilitées par l’Université du Manitoba, sur une vaste cohorte de travailleuses du sexe de Nairobi, qui ont révélé que les deux tiers avaient le VIH/sida, un résultat étonnant à l’époque. Il a également montré que près de 10 % de ces travailleuses du sexe n’étaient pas infectées par le VIH, malgré de multiples expositions. L’observation d’une résistance naturelle au VIH a guidé les stratégies de développement de vaccins. Le Dr Plummer a poursuivi en faisant des recherches sur les mécanismes de résistance au VIH, les facteurs de risque de transmission hétérosexuelle du VIH et la transmission du VIH de la mère à l’enfant, et il a élaboré des stratégies de santé publique pour lutter contre les infections sexuellement transmissibles. Des recherches subséquentes ont montré qu’en plus de ces travailleuses du sexe, de nombreux groupes sont immunisés contre le VIH. Au cours des 16 années suivantes, le Dr Plummer est resté à Nairobi, et cela a conduit à une série d’études, de collaborations internationales et de certaines découvertes fondamentales sur la susceptibilité à l’infection et la transmissibilité du VIH. L’impact : Ses contributions originales et soutenues dans ce domaine ont débouché sur des stratégies novatrices de prévention du VIH internationalement reconnues qui sont employées dans le monde entier pour prévenir des milliers d’infections au VIH. Professeur émérite à l’Université du Manitoba, le Dr Plummer a fait œuvre de pionnier dans la recherche sur le VIH/sida grâce non seulement à ses travaux novateurs mais aussi à son leadership à titre de directeur scientifique du Laboratoire national de microbiologie à Winnipeg, où il a mené la réponse à de nombreuses épidémies, notamment par son soutien et son apport au développement des programmes de vaccination contre l’Ebola au Canada, au traitement du SRAS en 2003 et à la pandémie de grippe H1N1 en 2009.

Les travaux : En 2012, la Dre Charpentier et la Dre Doudna ont publié la description d’une nouvelle technologie révolutionnaire d’édition génomique qui utilise un ARN à guide unique conçu conjointement avec l’enzyme Cas9 de clivage de l’ADN pour manipuler facilement l’ADN génomique de cellules individuelles. La technologie CRISPR-Cas9 a fourni aux biologistes l’équivalent d’une trousse de chirurgie moléculaire pour inhiber, activer ou altérer facilement des gènes avec une efficacité et une précision élevées. Leur travail a collectivement mené à la découverte révolutionnaire du clivage de l’ADN au moyen de l’enzyme Cas9, une enzyme double guidée par l’ARN dont la capacité à couper l’ADN à double brin peut être programmée en modifiant la séquence de guidage de l’ARN. Reconnaissant qu’une telle activité pourrait être utilisée comme instrument moléculaire pour l’ingénierie de précision du génome de divers types de cellules, leurs équipes ont reconfiguré le guide naturel double de l’ARN en ARN à guide unique (ARNgu), créant un système à deux composantes facile à utiliser. L’impact : Cette technologie transforme les domaines de la génétique moléculaire, de la génomique, de l’agriculture et de la biologie environnementale. Les complexes Cas9 guidés par l’ARN sont des agents d’ingénierie efficaces des génomes chez les animaux, les plantes, les champignons et les bactéries. La technologie CRISPR-Cas9 est utilisée dans des milliers de laboratoires à travers le monde pour faire avancer la recherche biologique grâce à une ingénierie précise des cellules et des organismes.

Les travaux : En 2012, la Dre Charpentier et la Dre Doudna ont publié la description d’une nouvelle technologie révolutionnaire d’édition génomique qui utilise un ARN à guide unique conçu conjointement avec l’enzyme Cas9 de clivage de l’ADN pour manipuler facilement l’ADN génomique de cellules individuelles. La technologie CRISPR-Cas9 a fourni aux biologistes l’équivalent d’une trousse de chirurgie moléculaire pour inhiber, activer ou altérer facilement des gènes avec une efficacité et une précision élevées. Leur travail a collectivement mené à la découverte révolutionnaire du clivage de l’ADN au moyen de l’enzyme Cas9, une enzyme double guidée par l’ARN dont la capacité à couper l’ADN à double brin peut être programmée en modifiant la séquence de guidage de l’ARN. Reconnaissant qu’une telle activité pourrait être utilisée comme instrument moléculaire pour l’ingénierie de précision du génome de divers types de cellules, leurs équipes ont reconfiguré le guide naturel double de l’ARN en ARN à guide unique (ARNgu), créant un système à deux composantes facile à utiliser. L’impact : Cette technologie transforme les domaines de la génétique moléculaire, de la génomique, de l’agriculture et de la biologie environnementale. Les complexes Cas9 guidés par l’ARN sont des agents d’ingénierie efficaces des génomes chez les animaux, les plantes, les champignons et les bactéries. La technologie CRISPR-Cas9 est utilisée dans des milliers de laboratoires à travers le monde pour faire avancer la recherche biologique grâce à une ingénierie précise des cellules et des organismes.

Les travaux : La recherche du Dr Barrangou et du Dr Horvath a porté sur la compréhension de la base génétique des propriétés favorables à la santé et technologiques de bactéries bénéfiques utilisées dans les fermentations alimentaires. Avec leurs collègues, ils ont établi que le système CRISPR-Cas offre une immunité adaptative contre les virus dans les bactéries, où il reconnaît l’ADN étranger et utilise un scalpel moléculaire spécial pour le cibler et le détruire. Ils ont également démontré que les faisceaux CRISPR capturent l’ADN viral pour la vaccination naturelle contre les bactériophages. Enfin, ils ont démontré que les gènes cas sont impliqués dans le ciblage de séquences spécifiques et le clivage de l’ADN. L’impact : Leur découverte a établi les CRISPR-Cas en tant que système immunitaire adaptatif des bactéries et a eu un profond impact sur le milieu scientifique, ouvrant la voie à un nouveau champ de recherche. Cela a incité d’autres chercheurs à étudier les CRISPR plus attentivement. Les principaux avantages du système CRISPR par rapport à d’autres techniques d’édition génomique est sa rapidité, sa précision, son efficacité et son coût relativement bas. Et, comme la communauté scientifique l’a démontré au cours des dernières années, il est transférable à de nombreux types d’organismes vivants. La liste des applications possibles comprend l’édition génomique, la production antibactérienne et antimicrobienne, la sécurité alimentaire, la production alimentaire et la sélection végétale.

Les travaux : La recherche du Dr Barrangou et du Dr Horvath a porté sur la compréhension de la base génétique des propriétés favorables à la santé et technologiques de bactéries bénéfiques utilisées dans les fermentations alimentaires. Avec leurs collègues, ils ont établi que le système CRISPR-Cas offre une immunité adaptative contre les virus dans les bactéries, où il reconnaît l’ADN étranger et utilise un scalpel moléculaire spécial pour le cibler et le détruire. Ils ont également démontré que les faisceaux CRISPR capturent l’ADN viral pour la vaccination naturelle contre les bactériophages. Enfin, ils ont démontré que les gènes cas sont impliqués dans le ciblage de séquences spécifiques et le clivage de l’ADN. L’impact : Leur découverte a établi les CRISPR-Cas en tant que système immunitaire adaptatif des bactéries et a eu un profond impact sur le milieu scientifique, ouvrant la voie à un nouveau champ de recherche. Cela a incité d’autres chercheurs à étudier les CRISPR plus attentivement. Les principaux avantages du système CRISPR par rapport à d’autres techniques d’édition génomique est sa rapidité, sa précision, son efficacité et son coût relativement bas. Et, comme la communauté scientifique l’a démontré au cours des dernières années, il est transférable à de nombreux types d’organismes vivants. La liste des applications possibles comprend l’édition génomique, la production antibactérienne et antimicrobienne, la sécurité alimentaire, la production alimentaire et la sélection végétale.

Les travaux : M. Ohsumi a été la première personne à observer visuellement la fonction de l’autophagie (auto-alimentation), par lequel les cellules nettoient leurs déchets internes, en tuant les organismes envahisseurs et en maintenant un environnement cellulaire sain. Cette fonction opère comme un système de recyclage cellulaire servant à maintenir l’homéostasie dans le corps. Il a ensuite précisé le mécanisme de l’autophagie et les gènes en cause. L’impact : L’autophagie est maintenant considérée comme un système de recyclage cellulaire vital qui pourrait se révéler utile dans le développement futur de traitements pour les maladies neurodégénératives telles que l’Alzheimer, le cancer et d’autres troubles liés au vieillissement. Les résultats de la recherche du professeur Ohsumi ont depuis été appliqués aussi à l’autophagie chez les animaux, et de nombreux chercheurs travaillent maintenant à préciser davantage le mécanisme moléculaire et la signification physiologique de ce processus.

Lewis C. Cantley, Ph.D., est professeur Margaret et Herman Sokol et directeur du Sandra et Edward Meyer Cancer Center au Weill Cornell Medical College / New York Presbyterian Hospital. Il a grandi en Virginie occidentale et a reçu son diplôme du West Virginia Wesleyan College en 1971. Lewis Cantley a obtenu un doctorat en chimie biophysique de l’Université Cornell en 1975 et a fait un stage de formation postdoctorale à l’Université Harvard. Avant de prendre le poste qu’il occupe au Weill Cornell, il a enseigné et fait de la recherche en biochimie, en physiologie et en biologie du cancer à Boston, plus récemment au Beth Israel Deaconess Medical Center et à l’École de médecine de l’Université Harvard. Son laboratoire à découvert la voie PI 3-kinase qui joue un rôle essentiel dans la signalisation de l’insuline et dans les cancers. Lewis Cantley a été élu à l’Académie américaine des arts et des sciences en 1999 et à l’Académie nationale des sciences en 2001. Parmi les autres récompenses qu’il a reçues, mentionnons le Prix Avanti ASBMB pour la recherche sur les lipides en 1998, le Prix Heinrich Weiland pour la recherche sur les lipides en 2000, le Prix Caledonian de la Société royale d’Edimbourg en 2002, le Prix international de la Fondation Pezcoller-AACR pour la recherche sur le cancer en 2005, le Prix Rolf Luft de l’Institut Karolinska, à Stockholm, pour la recherche sur le diabète et l’endocrinologie en 2009, le Prix Pasrow pour la recherche sur le cancer en 2011, le Prix Breakthrough in Life Sciences en 2013 et le Prix Jacobaeus de l’Institut Karolinska pour la recherche sur le diabète en 2013 . Il a été élu à l’Institut de médecine 2014.

Michael N. Hall est né (1953) à Porto Rico et a grandi en Amérique du Sud (Venezuela et Pérou). Il a obtenu son doctorat de l’Université Harvard et a été boursier postdoctoral à l’Institut Pasteur (Paris, France) et à l’Université de Californie, San Francisco. Il a rejoint le Biozentrum de l’Université de Bâle (Suisse) en 1987 où il est actuellement professeur et ancien président du département de biochimie. Michael Hall est un pionnier des domaines de la signalisation TOR et du contrôle de la croissance cellulaire. En 1991, Mr Hall et ses collègues ont découvert la TOR (cible de la rapamycine), et ont subséquemment élucidés son rôle de contrôleur central de la croissance cellulaire et du métabolisme. La TOR est une protéine kinase conservée activée par l’insuline et des nutriments. La découverte de la TOR a conduit à une évolution fondamentale de la façon dont nous concevons la croissance cellulaire. Celle-ci n’est pas un processus spontané qui se déroule uniquement lorsque les blocs de construction (nutriments) sont disponibles, mais plutôt un processus plastique étroitement réglementé, contrôlé par des voies de signalisation dépendantes de la TOR. En tant que contrôleur central de la croissance cellulaire et du métabolisme, la TOR joue un rôle clé dans le développement et le vieillissement, et elle est impliquée dans des troubles tels que le cancer, les maladies cardiovasculaires, le diabète et l’obésité. Michael Hall est membre de l’Académie nationale des sciences des États-Unis, et il a reçu de nombreuses récompenses, dont le Prix Cloëtta pour la recherche biomédicale (2003), le Prix Louis-Jeantet de médecine (2009), le Prix Marcel Benoist pour les sciences ou les sciences humaines (2012) et le Prix Breakthrough in Life Sciences (2014). Il a siégé à plusieurs conseils consultatifs éditoriaux et scientifiques. Il vit avec son épouse Sabine (née Carrère) et leurs filles Zoé et Léa, à Bâle.

Lynne E. Maquat est titulaire de la chaire J. Lowell Orbison, et professeure de biochimie et de biophysique et professeure d’oncologie à l’École de médecine et de dentisterie, directrice du Center for RNA Biology: From Genome to Therapeutics et présidente des femmes diplômées en sciences à l’Université de Rochester, à Rochester, New York. Après avoir obtenu son doctorat de l’Université du Wisconsin à Madison et fait de la recherche postdoctorale au McArdle Laboratory for Cancer Research à Madison, elle est passée au Roswell Park Cancer Institute à Buffalo avant de déménager son laboratoire à l’Université de Rochester. La professeure Maquat est connue pour ses études des cellules de mammifères sur la dégradation des ARN messagères à médiation non-sens (NMD), dont elle a fait rapport pour la première fois en 1981 par le biais d’études sur l’anémie hémolytique bo-thalassémique, à partir desquelles elle a par la suite découvert la ronde pionnière de traduction, le complexe de jonction exon (EJC), et comment l’EJC marque les ARNm pour un premier cycle de traduction de contrôle de la qualité qui se produit en grande partie lorsque les ARN messagères comme nouvellement synthétisées entrent dans le cytoplasme. Elle continue à faire des contributions fondamentales sur les mécanismes de la NMD et d’une autre voie qu’elle a découverte et nommée dégradation des ARNm à médiation Staufen (SMD). Son travail sur la SMD a défini de nouveaux rôles pour les longs ARN non-codants et de petits éléments intercalés chez les humains et les rongeurs, dévoilant la complexité des interactions ARN-ARN qui comprennent d’importantes voies de régulation géniques post-transcriptionnelles au cours du développement et de la différenciation des cellules de mammifères. La professeure Maquat a siégé à des comités de rédaction, y compris ceux de RNA, Mol. Cell Biol., RNA Biol. et Methods, comme administratrice, trésorière/secrétaire et présidente élue de la RNA Society, comme membre du Comité d’information publique de l’American Society for Cell Biology, et comme présidente de la section des études des NIH. Elle est membre élue de l’Association américaine pour l’avancement des sciences (2006), membre élue de l’Académie américaine des arts et des sciences (2006) et de l’Académie nationale des sciences (2011), et chercheure Batsheva de Rothschild de l’Académie israélienne des sciences et des sciences humaines (2012). La professeure Maquat a reçu le prix C. William Rose de l’American Society for Biochemistry and Molecular Biology (2014) pour ses activités de recherche et de mentorat, en particulier son appui à la promotion des femmes en science. FAQ

Peter Piot, M.D., Ph.D., FRCP, FMedSci, est directeur de la London School of Hygiene & Tropical Medicine et professeur de santé mondiale. Il a été le premier directeur général de l’ONUSIDA, sous-secrétaire général de l’Organisation des Nations Unies de 1995 à 2008, et directeur associé du Programme mondial sur le sida de l’OMS. Clinicien et microbiologiste de formation, il a co-découvert le virus Ebola au Zaïre en 1976 et, par la suite, il a dirigé des travaux de recherche sur le sida, la santé des femmes et les infections transmises sexuellement, principalement en Afrique. Il a occupé des postes d’enseignement à l’Institut de Médecine Tropicale d’Anvers, l’Université de Nairobi, l’Université de Washington et l’Imperial College de Londres, et il a été chercheur principal à la Fondation Bill & Melinda Gates. Il a occupé la chaire « Le savoir contre la pauvreté » en 2009/2010 au Collège de France, à Paris. Il est membre de l’Institut de médecine de l’Académie nationale des sciences des États-Unis et de l’Académie royale de Médecine de sa Belgique natale, et il est membre de l’Academy of Medical Sciences et du Royal College of Physicians. Il a été président de la Société internationale sur le sida, et de la Fondation du roi Baudouin. En 1995, il a été anobli baron par le Roi Albert II de Belgique. Il a reçu de nombreux prix pour ses recherches et services, dont le Prix Nelson Mandela pour la santé et les droits humains, la Médaille F. Calderone, le Prix Hideyo Noguchi pour l’Afrique, le Prix en santé publique du Prince Mahidol, et le Prix Canada Gairdner en santé mondiale 2015. Il a publié plus de 570 articles scientifiques et 16 ouvrages, dont ses mémoires « Pas de temps à perdre ».

La Dre Janet Rossant, chef de la recherche à l’Hôpital SickKids et spécialiste de renommée mondiale en biologie du développement, est la définition même d’une pionnière. Largement connue pour ses études sur les gènes qui contrôlent le développement embryonnaire chez la souris, la Dre Rossant a été la première à employer des techniques pour suivre l’évolution des cellules et la modification des gènes dans les embryons. Ces travaux conservent toute leur pertinence dans la recherche génétique médicale. Ses recherches actuelles portent sur le développement des cellules souches et de la différenciation des cellules dans l’embryon en développement, des domaines importants pour l’étude des malformations congénitales ainsi que pour la médecine régénérative. Fermement installée à l’avant-garde du changement technologique, la Dre Rossant a placé SickKids sur la ligne de front en recherche génétique dans le monde. La Dre Rossant a reçu sa formation aux universités d’Oxford et de Cambridge, au Royaume-Uni, et travaille au Canada depuis 1977, d’abord à l’Université Brock, puis à l’Institut de recherche Samuel Lunenfeld de l’Hôpital Mount Sinai à Toronto, de 1985 à 2005. Elle s’est jointe à SickKids en 2005. Les contributions à la science de la Dre Rossant ont été reconnues par de nombreux prix, dont la médaille Ross G. Harrison (prix pour l’ensemble de son œuvre) de la Société internationale des biologistes du développement, le Prix Killam en sciences de la santé, le Prix March of Dimes en biologie du développement, la Médaille Conklin de la Société de biologie du développement et le prix Michael Smith des IRSC pour la recherche en santé. Elle est membre de deux sociétés royales, de Londres et du Canada, et est associée étrangère de l’Académie nationale des sciences des États-Unis. Plus récemment, la Dre Rossant s’est vue décerner en octobre 2014 le 10e Prix ISTT de la Société internationale des technologies transgéniques, à Edimbourg, en Écosse.

Shimon Sakaguchi est professeur émérite à la World Premier International Research Initiative (WPI)-Immunology Frontier Research Center (IFReC) de l’Université d’Osaka, au Japon. Il est un immunologiste dont les travaux sur le contrôle des réponses immunitaires ont été reconnus. Le Dr Sakaguchi est notamment connu pour sa découverte de cellules T régulatrices, un constituant indispensable du système immunitaire pour le maintien de l’autotolérance immunitaire et l’homéostasie. Shimon Sakaguchi est né au Japon en 1951; il a obtenu son diplôme de médecine en 1976, puis en 1982, un doctorat de l’Université de Kyoto, au Japon, où il a reçu une formation de pathologiste et d’immunologiste. Après des études postdoctorales à l’Université Johns Hopkins et l’Université Stanford à titre de Lucille P. Markey Scholar, il a été professeur adjoint au Département d’immunologie du Scripps Research Institute. Il est retourné au Japon en 1991 et a poursuivi ses recherches en immunologie à l’Institut RIKEN comme chercheur de l’Agence des sciences et de la technologie du Japon, puis comme chef du Département d’immunopathologie du Tokyo Metropolitan Institute of Gerontology. De 1998 à 2011, il a été professeur et président du Département de pathologie expérimentale à l’Institute for Frontier Medical Sciences, de l’Université de Kyoto, et il a servi comme directeur de cet établissement pendant plusieurs années. En 2011, il a déménagé son laboratoire à l’Université d’Osaka et a assumé son poste actuel de professeur universitaire émérite de l’Université d’Osaka.

Le Dr Harold F. Dvorak est directeur fondateur du Centre de recherche en biologie vasculaire (CVBR) au Beth Israël Deaconess Medical Center (BIDMC) et professeur émérite Mallinckrodt de pathologie à l’École de médecine de l’Université Harvard. En 1983, le Dr Dvorak et ses collègues ont été les premiers à démontrer que les cellules tumorales sécrétaient un facteur de croissance vasculaire endothélial (FCVE), appelé à l’époque facteur de perméabilité vasculaire ou VPF. Cette découverte fondamentale a fourni le fondement moléculaire pour le domaine de l’angiogenèse. Le Dr Dvorak a ensuite fait l’observation extrêmement importante que les tumeurs se comportent comme des « plaies qui ne guérissent pas » car les réponses vasculaires et stromales qu’elles induisent imitent étroitement celles de la guérison des plaies. Plus récemment, son travail a caractérisé les différents types de vaisseaux sanguins que les tumeurs génèrent et les mécanismes moléculaires par lesquels ils se forment. Le Dr Dvorak a enseigné pendant de nombreuses années à l’École de médecine de l’Université Harvard et a souvent prononcé des allocutions comme professeur invité ainsi qu’à de nombreuses conférences scientifiques nationales et internationales. Il est membre de l’Association américaine pour l’avancement de la science et de la Fondation nationale pour la recherche sur le cancer et il a servi comme président de l’American Society for Investigative Pathology, laquelle lui a décerné le Prix Rous-Whipple 2002, et, en 2013, le Prix de la canne au pommeau d’or pour ses réalisations scientifiques. En 2005, il a reçu le Grand Prix Lefoulon-Delalande de l’Institut de France et, en 2006, le premier Prix Albert Szent-Györgyi pour le progrès dans la recherche sur le cancer, de la Fondation nationale pour la recherche sur le cancer (NFCR). Formé à l’Université de Princeton et à l’École de médecine de l’Université Harvard, il a été résident en pathologie à l’Hôpital général du Massachusetts et a fait des recherches postdoctorales aux National Institutes of Health. Il est membre du corps professoral de l’École de médecine de l’Université Harvard depuis 1967 et attaché au BIDMC depuis 1979. Suivant son départ après 26 ans comme président de la pathologie au BIDMC en juillet 2005, le Dr. Dvorak a consacré ses efforts à l’édification du CVBR, tout en poursuivant ses recherches.

Le Dr Ferrara a obtenu un diplôme de médecine en 1981 de l’École de médecine de l’Université de Catane, en Italie. Après avoir terminé ses études postdoctorales à l’Université de la Californie à San Francisco, il s’est joint à la société Genentech Inc. en 1988. Il y a passé près de 25 ans, travaillant sur la caractérisation moléculaire et l’application thérapeutique du VEGF-A, qui a mené à l’élaboration du bevacizumab, le premier agent anti-angiogénique approuvé par la FDA pour le traitement du cancer. Ses recherches ont également mené à l’élaboration du ranibizumab, qui a été approuvé par la FDA pour le traitement de plusieurs troubles néovasculaires intraoculaires. En janvier 2013, le Dr Ferrara s’est joint à l’Université de la Californie à San Diego comme professeur émérite de pathologie, professeur émérite adjoint d’ophtalmologie et sous-directeur principal des sciences fondamentales au Moores Cancer Center. Le Dr. Ferrera a rédigé plus de 300 publications scientifiques. Il est récipiendaire de nombreux prix, dont le Prix Lefoulon-Delalande de l’Institut de France, le Prix Passano, le Prix pour la recherche sur le cancer de General Motors, le Prix ASCO en science de l’oncologie, le Prix international de la Fondation Pezcoller-AACR, la Bourse de la recherche médicale clinique Lasker-deBakey, le Prix Dr Paul Janssen, le Prix Economist Innovation et le Prix inaugural pour une percée en sciences de la vie. Dr Ferrara est membre de l’Académie nationale des sciences des États-Unis depuis 2006.

Après une formation en médecine et constatant que la recherche était la voie vers l’amélioration de la thérapie, il a étudié en vue d’obtenir un doctorat en immunologie à l’Institut Walter et Eliza Hall de Melbourne auprès du professeur Sir Gus Nossal. Il a appris à optimiser les réponses immunitaires en culture de tissus et a également étudié de puissants médiateurs intercellulaires, des molécules éventuellement identifiées comme les cytokines, l’auto-immunité et l’immunorégulation. En 1983, tout en travaillant à l’Unité d’immunologie tumorale d’Av Mitchison à l’ICRF, au Collège universitaire de Londres, et en réfléchissant aux nouvelles observations sur le CMH de classe II régulé positivement dans les sites locaux d’auto-immunité (p. ex. la thyroïde), il a émis l’hypothèse que cela reflétait une augmentation de la présentation d’antigène. Étant donné que les cytokines, notamment les interférons, régulent positivement les antigènes CMH, il a émis en 1983 l’hypothèse que la présentation de cytokines et d’antigènes régulées positivement est une étape clé dans l’apparition d’une maladie auto-immune chronique. Il s’agissait d’une hypothèse vérifiable, et celle-ci a été vérifiée avec succès sur la thyroïdite de Grave vers 1985-1986. Cela a mené à une collaboration avec Ravinder Maini, un déménagement à l’Institut Kennedy et l’étude de ce qui constituaient les cytokines critiques dans la maladie auto-immune humaine la plus accessible, la polyarthrite rhumatoïde. De nouvelles méthodes ont été élaborées pour évaluer quelles cytokines sont produites localement, faisant ressortir que de nombreuses cytokines pro-inflammatoires sont produites. Afin de déterminer ce qui constituait la meilleure cible, il a analysé la régulation des cytokines dans le tissu synovial dissocié de la polyarthrite rhumatoïde et trouvé que le blocage de la TNF régulait à la baisse l’IL-1 et d’autres cytokines pro-inflammatoires, ce qui indique que la TNF était la cible thérapeutique longuement recherchée. Cela a été validé dans l’arthrite de la souris, avec un traitement administré après l’apparition de la maladie. Il était donc justifié de procéder à un essai clinique de validation de principe de la thérapie anti-TNF, et Sir Marc a été un chef de file, avec son collègue le professeur Sir Ravinder Maini, de cet essai et d’autres essais cliniques subséquents qui ont conduit à l’approbation de la thérapie anti-TNF pour la polyarthrite rhumatoïde. Cette réussite et celles des essais d’autres anticorps contre la TNF ont fait en sorte que les anti-TNF ont été la classe de médicaments la plus vendue à partir de 2012. Sir Marc a succédé à Ravinder Maini au poste de directeur de l’Institut de rhumatologie Kennedy en 2002. Ces travaux ont mené à son élection à diverses académies nationales des sciences (p. ex., la Société royale, l’Académie australienne des sciences et l’Académie nationale des sciences des États-Unis, et à l’obtention de plusieurs prix prestigieux, la plupart du temps avec son collègue Sir Ravinder Maini, par exemple le Prix Crafoord de l’Académie royale de Suède, le Prix Albert Lasker de recherche médicale clinique, le Prix Ernst Schering et le Prix Paul Janssen.

Né de parents indiens, Sir Ravinder Maini a reçu son éducation initiale en Ouganda et a résidé en permanence au Royaume-Uni depuis 1955. Après ses études secondaires à Londres, il a étudié la médecine à l’Université de Cambridge et à l’Hôpital Guy de Londres (diplôme B.A., M.B., B.Chir., 1962). Il a poursuivi une formation clinique de troisième cycle et a reçu une bourse de recherche en immunologie clinique. Tout au long de sa carrière professionnelle qui a débuté en 1970, il a combiné la pratique de clinicien-chercheur en rhumatologie et en médecine interne et la recherche immunologique en laboratoire. De 1990 à 2002, il a été professeur et directeur scientifique/chef de l’Institut de rhumatologie Kennedy, à Londres. Ses recherches ont porté sur les mécanismes immunologiques et inflammatoires et le traitement des maladies rhumatismales auto-immunes. Sa recherche « du laboratoire au chevet du patient », menée en collaboration avec Sir Marc Feldmann, a débuté en 1985 et permis le développement de l’immunothérapie anti-TNF contre la polyarthrite rhumatoïde. Il a été invité comme conférencier d’honneur lors de réunions scientifiques internationales, a publié plus de 480 articles dans des revues scientifiques, a siégé au comité de rédaction des revues sur l’immunologie et la rhumatologie, et est actuellement corédacteur en chef de la revue à accès libre Arthritis Research and Therapy. Depuis sa retraite, il est professeur invité à l’Institut de rhumatologie Kennedy à Oxford. Il continue de servir à titre de consultant et de conseiller auprès de l’industrie biotechnologique et pharmaceutique, ainsi que d’organismes nationaux d’octroi de subventions. Il est fiduciaire d’organismes caritatifs du domaine médical et est actuellement administrateur et président de la fiducie Kennedy Rheumatology Research, au Royaume-Uni, et fiduciaire de la fiducie Sir Jules Thorn. Ses contributions à la recherche ont été reconnues par l’obtention d’un titre de chevalier (2003) conféré par la reine Elizabeth, et son élection à des sociétés scientifiques : Il est membre de la Société royale de Londres (FRS), membre de l’Académie des sciences médicales (FMedSci), membre associé étranger de l’Académie des sciences des États-Unis, membre des Collèges royaux de Londres et d’Édimbourg et membre honoraire du Collège Sidney Sussex; il a reçu des doctorats honorifiques de l’Université de Glasgow et de l’Université René Descartes, à Paris; il a aussi reçu le titre de chercheur émérite, décerné par le Collège de rhumatologie des États-Unis; enfin, il est membre honoraire de sociétés scientifiques au Royaume-Uni, en Europe et en Australie. Suite à l’identification des TNF comme cible thérapeutique et le transfert de la thérapie anti-TNF à la clinique, les professeurs Maini et Feldmann ont conjointement reçu de nombreux prix, notamment le Prix Crafoord de l’Académie royale des sciences de Suède, le Prix Lasker pour la recherche clinique, le Prix Dr Paul Janssen en recherche biomédicale, le Prix Ernst Schering et, en 2014, ils ont été sélectionnés comme récipiendaires du Prix international Canada Gairdner.

Le Dr Allison est professeur et président du Département d’immunologie, directeur général de la Plate-forme d’immunothérapie et directeur adjoint du Centre David H. Koch pour la recherche appliquée sur les cancers génito-urinaires au MD Anderson Cancer Center de l’Université du Texas. En poste au MD Anderson Cancer Center depuis novembre 2012, le Dr Allison s’emploie à mettre en place une équipe de cliniciens et de médecins-chercheurs pour accélérer la progression des thérapies combinatoires à base immunitaire vers les essais cliniques. Depuis son arrivée, il a déjà reçu du financement de Stand Up to Cancer et de l’Institut de recherche sur le cancer (SU2C/CRI) pour diriger une équipe chevronnée en recherche sur l’immunologie translationnelle en vue de faciliter le développement clinique de formes nouvelles et améliorées d’immunothérapie du cancer. Le Dr Allison a obtenu un B.S. en microbiologie et un doctorat en sciences biologiques de l’Université du Texas à Austin, et il a ensuite effectué un stage postdoctoral au Département d’immunologie moléculaire de la Scripps Clinic and Research Foundation en Californie. Il a commencé sa carrière universitaire comme professeur adjoint au Département de biochimie de l’Université du Texas, à la Division Science-Park Research, à Smithville, au Texas, et a rapidement atteint le rang de professeur au sein de la Division d’immunologie du Département de biologie moléculaire et cellulaire de l’Université de la Californie, à Berkeley. Le Dr Allison a été recruté au MD Anderson Cancer Center alors qu’il travaillait au Memorial Sloan-Kettering Cancer Center, où il a été président du Programme d’immunologie, immunologiste traitant et directeur du Ludwig Center for Cancer Immunotherapy, et professeur au Collège de médecine Weill de l’Université Cornell depuis 2004. Le Dr Allison a à son actif plus de 260 publications, y compris des articles dans Nature, Science, Cell, Immunity, Cancer Cell et Blood. Il a reçu de nombreux prix en reconnaissance de son travail pionnier, dont le Prix de la Dana Fondation pour la recherche en immunologie humaine (2008), le Prix Richard V. Smalley M.D. Memorial Lectureship (2010), un Prix de l’Association américaine des immunologistes pour l’ensemble de ses réalisations (2011), le Prix Roche en immunologie et immunothérapie du cancer (2011), le Prix Novartis en immunologie clinique (2013) et le Prix de la percée en sciences de la vie (2013).

Titia de Lange a reçu une formation en biochimie à l’Université d’Amsterdam et à l’Institut néerlandais du cancer. Au cours de sa formation de premier cycle, elle a travaillé sur l’expression génique des globines avec Richard Flavell au NIMR, à Mill Hill, avant de rejoindre Piet Borst, en 1981, à l’Institut néerlandais du cancer comme étudiante diplômée. En 1985, elle a obtenu un doctorat (cum laude) et a rejoint Harold Varmus à l’Université de la Californie à San Francisco pour poursuivre des études postdoctorales. Avec ce dernier, elle a isolé l’ADN télomérique humaine et a été la première à montrer que les télomères tumorales raccourcissent. En 1990, elle a été nommée professeure adjointe à l’Université Rockefeller, où elle a été promue au rang de professeure en 1997. Elle est présentement professeure Leon Hess, professeure-chercheure à l’American Cancer Society et directrice du Anderson Cancer Research Center de l’Université Rockefeller. Titia De Lange est membre (étrangère) de l’EMBO, de l’Académie nationale des sciences des États-Unis, de l’Académie royale néerlandaise des sciences, de l’Académie américaine des arts et des sciences, de l’Association américaine pour l’avancement des sciences, de la Société américaine de microbiologie, de l’Académie des sciences de New York et de l’Institut de médecine. Elle a reçu le premier Prix Paul Marks pour la recherche sur le cancer, le Prix du Massachusetts General Hospital Cancer Center, les Charlotte Friend et G.H.A Clowes Prix de l’AACR, le Prix Vilcek, le Prix Vanderbilt, le Prix Dr. HP Heineken, et le Prix pour la percée en sciences de la vie. Elle est titulaire d’un doctorat honorifique de l’Université d’Utrecht. Titia De Lange a siégé aux conseils scientifiques consultatifs de plusieurs établissements universitaires américains et européens, dont le MSKCC, le CSHL, le Cancer Center du MIT, l’IMP de Vienne, le CRUK / LRI de Londres et l’Institut Ludwig pour la recherche sur le cancer. Elle siège également à plusieurs comités d’octroi de bourses et subventions, y compris le jury du Prix Lasker, le comité de sélection du Prix Vilcek et le comité de sélection du Prix Pearl Meister Greengard.

Les travaux de Salim Yusuf, qui se sont poursuivis sur plus de 35 ans, ont considérablement influencé la prévention et le traitement des maladies cardiovasculaires à l’échelle mondiale. Diplômé en médecine à Bangalore en 1976, il a obtenu une bourse Rhodes et reçu un doctorat en philosophie de l’Université d’Oxford. À cette époque, en collaboration avec Richard Peto et Peter Sleight, il a élaboré les concepts des grands essais simples et des méta-analyses. Il a coordonné l’essai ISIS (qui a établi la structure pour les futurs travaux de collaboration internationale sur les maladies cardiovasculaires) démontrant le rôle des bêtabloquants pour l’infarctus du myocarde, et a siégé au comité de direction de tous les essais subséquents dans le cadre de l’ISIS. En 1984, il s’est joint aux National Institutes of Health, à Bethesda, aux États-Unis, où il a été un chef de file dans l’essai SOLVD (établissant l’utilité des inhibiteurs de l’ECA pour la dysfonction LV) et l’essai DIG (visant à clarifier le rôle de la digitaline). En 1992, il est passé à l’Université McMaster, où il a mis sur pied un programme international de recherche sur les maladies cardiovasculaires et la prévention, qui a mené à la création de l’Institut de recherche en santé de la population, qu’il dirige toujours. Ses essais thérapeutiques ont permis de préciser le rôle des inhibiteurs de l’ECA dans la prévention des maladies cardiovasculaires (étude HOPE), des bithérapies antiplaquettaires des syndromes coronariens aigus (étude CURE), ainsi que le rôle des nouveaux antithrombotiques et des interventions invasives. L’IRSP a récemment été cité par SCImago comme étant l’établissement canadien ayant le plus grand impact et le 7ème plus important à ce chapitre dans le monde. Les travaux épidémiologiques du Dr Yusuf ont été menés dans plus de 60 pays, sur tous les continents habités, et ont démontré que la majorité des risques de maladie cardiovasculaire et cérébrovasculaire est attribuable au même petit groupe de facteurs de risque. Le Dr Yusuf dirige actuellement la plus grande étude jamais entreprise sur le rôle des changements sociétaux dans les MCV qui rejoint 155 000 personnes dans 700 collectivités de 22 pays à revenu élevé, intermédiaire ou faible. Ces études ont conduit à une meilleure compréhension de l’influence des changements sociétaux sur les comportements et les facteurs de risque, et la façon dont ils entraînent des maladies cardiovasculaires. Au cours des trois dernières décennies, il a contribué à renforcer les capacités de recherche clinique et d’étude de population à travers le Canada (d’abord au sein de la Collaboration canadienne de cardiologie et, plus récemment, de CANNeCTIN) et dans le monde en établissant des réseaux regroupant plus de 1500 sites dans 85 pays sur tous les continents habités. Il a formé plus de 50 chercheurs, dont plusieurs sont devenus des chefs de file nationaux ou internationaux reconnus en recherche médicale. Il a contribué au développement d’établissements ou de grands programmes de recherche au Canada, en Inde, en Argentine, au Brésil, en Afrique du Sud, en Arabie saoudite, en Malaisie et en Chine. Il détient une chaire de la Fondation des maladies du cœur de l’Ontario, et a été chercheur principal des Instituts de recherche en santé du Canada (1999-2004). Il a reçu plus de 35 prix nationaux et internationaux en recherche, il a été intronisé au sein de la Société royale du Canada, nommé officier de l’Ordre du Canada et, en 2014, intronisé au Temple de la renommée médicale canadienne. Le Dr Yusuf a publié plus de 800 articles dans des revues soumises à l’examen de pairs, devenant le deuxième chercheur le plus cité dans le monde en 2011. Il est président élu de la Fédération mondiale du cœur, où il a lancé un programme de chefs de file émergents dans 100 pays en vue de réduire de moitié le fardeau des maladies cardiovasculaires à l’échelle mondiale d’ici une génération.

Le Dr Harvey Alter a obtenu son diplôme de médecin à la Faculté de médecine de l’Université de Rochester et a acquis une formation en médecine interne à l’Hôpital Strong Memorial et à l’Hôpital de l’Université de Washington, à Seattle. En 1961, il s’est joint aux National Institutes of Health (NIH) comme associé-clinicien. Il a ensuite passé plusieurs années à l’Université de Georgetown, retournant aux NIH en 1969 comme chercheur principal au Département de médecine transfusionnelle du Centre clinique, où il est devenu par la suite chef des études cliniques et directeur adjoint de la recherche. Le Dr Alter a co-découvert l’antigène d’Australie, un élément clé dans la détection du virus de l’hépatite B. Subséquemment, le Dr Alter a dirigé un projet au Centre clinique des NIH qui a mené à la création d’un entrepôt d’échantillons de sang utilisés pour découvrir les causes de la transmission de l’hépatite lors d’une transfusion et en réduire les risques. Il a été chercheur principal dans le cadre des études qui ont identifié l’hépatite autre que A et B, aujourd’hui appelée l’hépatite C. Son travail a contribué à établir le fondement scientifique des programmes de dépistage des donneurs de sang, qui ont réduit l’incidence de l’hépatite post-transfusionnelle à près de zéro. Le Dr Alter a reçu le Prix clinique Lasker en 2000. En 2002, il est devenu le premier scientifique du Centre clinique des NIH à être élu à l’Académie nationale des sciences (NAS). La même année, le Dr Alter a été élu à l’Institut de médecine.

Après avoir obtenu son diplôme de l’Université de San Jose, en 1964, le Dr Bradley a été recruté par le Service de santé publique des États-Unis (USPHS) afin d’élaborer des méthodes de détection de toute une variété de composés cancérigènes dans l’atmosphère, une tâche particulièrement dangereuse. À la fin de son service au USPHS, il a poursuivi ses études et obtenu un diplôme de maîtrise en biochimie de l’Université de la Californie et un doctorat de l’Université de l’Arizona. En 1971, il a été embauché par le Center for Disease Control (CDC) à Phoenix, en Arizona, pour étudier la possibilité que l’acide ascorbique abrège la durée des infections virales respiratoires. Ne pouvant observer un tel avantage, le Dr Bradley a ensuite centré ses efforts sur le virus de l’hépatite A et B, étudiant leur infectivité chez les primates non-humains. Ces études se sont déroulées entre 1972 et 1975 et ont conduit à l’identification d’un nouveau groupe de virus de l’hépatite. En 1975, son laboratoire a été contacté par un scientifique de Hyland Laboratories qui s’intéressait à l’identification possible d’un virus responsable de l’hépatite autre que A ou B chez plusieurs patients hémophiles. D’autres études menées dans les années 1970 et 1980 ont révélé la présence d’un flavivirus, ce qui a conduit à l’identification précoce de ce qui est maintenant connu comme le virus de l’hépatite C (VHC). Bien qu’un fragment du génome du VHC ait été identifié en 1987, l’annonce publique du clonage réussi du VHC n’est survenue qu’en 1989.

Le Dr Stephen J. Elledge a fait ses études de premier cycle à l’Université de l’Illinois et a obtenu un doctorat en biologie de l’Institut de Technologie du Massachusetts (MIT) en 1983. En 1989, il a été nommé professeur adjoint au Département de biochimie du Collège de médecine Baylor. En 1993, il est devenu chercheur au Howard Hughes Medical Institute et, en 1995, a été promu au poste de professeur. En 2003, il s’est joint au Département de génétique de l’École de médecine de l’Université Harvard et à la Division de génétique de l’Hôpital Brigham and Women. Présentement, le Dr Elledge est professeur Gregor Mendel de génétique et de médecine à l’École de médecine de l’Université Harvard. En plus d’être un ancien boursier-chercheur Helen Hay Whitney, le Dr Elledge a été associé principal de l’American Cancer Society et chercheur-boursier Pew. Il a reçu de nombreux prix et distinctions pour ses recherches innovantes, dont le Prix Michael E. Debakey pour l’excellence en recherche (2002), le Prix GHA Clowes Memorial de l’Association américaine de recherche sur le cancer (2001), le Prix inaugural Paul Mark en recherche sur le cancer (2001), le Prix de biologie moléculaire de l’Académie nationale des sciences (2001), le Prix John B. Carter Jr. d’innovation technologique (2002), un Prix du mérite des NIH (2003), la Médaille de la Société américaine de génétique (2005), le Prix international Hans Sigrist de l’Université de Berne (2005), le Prix Dickson en médecine (2010), le Prix de l’American Italian Cancer Foundation pour l’excellence scientifique en médecine (2012) et le Prix Lewis Rosenstiel pour des travaux remarquables en sciences médicales fondamentales (2013). En 2003, le Dr Elledge a été élu à l’Académie nationale des sciences et à l’Académie américaine des arts et des sciences; en 2005, il a été élu à l’Académie américaine de microbiologie, et, en 2006, à l’Institut de médecine.

Sir Gregory Winter est membre du Laboratoire de biologie moléculaire ((LMB) du Conseil de recherches médicales, à Cambridge et, jusqu’à récemment, il en était le directeur adjoint. Il est aujourd’hui maître du Collège Trinity, à Cambridge. Sir Gregory est diplômé de l’Université de Cambridge, avec spécialisation en chimie et en biochimie (1973). Il a poursuivi ses études au même établissement, où il a reçu un doctorat en 1976, se spécialisant dans le séquençage des protéines et des acides nucléiques. Sir Gregory est un pionnier de la science de l’ingénierie des protéines; il s’est d’abord concentré sur les enzymes, puis sur les anticorps. Au LMB, il a inventé des techniques pour humaniser les anticorps de rongeurs en vue de leur utilisation comme agents thérapeutiques (1986) et, plus tard, pour produire des anticorps entièrement humains (1989) en utilisant des répertoires de gènes combinatoires. Ses inventions sont utilisées dans près de la moitié des produits à base d’anticorps que l’on retrouve sur le marché, y compris les anticorps humanisés Campath-1H, Herceptin, Avastin, Synagis, et le premier anticorps humain (Humira) à être approuvé par la Food and Drug Administration des États-Unis. Sir Winter est aussi un entrepreneur. Il est l’un des fondateurs de Cambridge Antibody Technology (1989) et de Domantis (2000). Ces deux sociétés ont été des pionnières dans l’utilisation des technologies de répertoire d’anticorps pour la production d’anticorps thérapeutiques entièrement humains. En 2006, Cambridge Antibody Technology Ltd a été acquise par AstraZeneca PLC, et Domantis Ltd a été acquise par GlaxoSmithKline PLC en 2006. Plus récemment, Sir Gregory a fondé Bicycle Therapeutics Ltd., une société de biotechnologie spécialisée dans le développement d’une nouvelle génération de produits biothérapeutiques.

Le Dr Hogg a obtenu son diplôme de médecine de l’Université du Manitoba en 1962, une maîtrise en médecine expérimentale de l’Université McGill en 1967, et un doctorat en médecine expérimentale de l’Université McGill en 1969. Tout au long de sa carrière, les recherches du Dr Hogg ont porté sur les mécanismes et les sites anatomiques de la maladie pulmonaire obstructive. Les recherches du Dr Hogg ont fait progresser les connaissances sur la façon dont fonctionne un poumon en santé et un poumon malade, y compris la physiopathologie de l’asthme et les effets nocifs du tabagisme et de la pollution. En 1977, le Dr Hogg a été recruté par l’Université de la Colombie-Britannique et l’Hôpital Saint-Paul, où il a mis sur pied un centre de renommée mondiale pour la recherche pulmonaire et cardio-vasculaire, qui est passé d’un stagiaire par an à environ une centaine aujourd’hui. En son honneur, ce laboratoire s’appelle maintenant le Centre de recherche James Hogg de l’Université de la Colombie-Britannique pour la recherche cardiovasculaire et pulmonaire. Officier de l’Ordre du Canada (2005), le Dr Hogg a été élu à la Société royale du Canada (1992) et au Temple de la renommée médicale canadienne (2010); ses travaux ont aussi été reconnus par tout un éventail de prix scientifiques. En 2003, il a été récipiendaire du Prix Chugai, de l’American Society for Investigative Pathology, et il a été honoré par l’American Thoracic Society à plusieurs reprises. La carrière professionnelle du Dr Hogg, consacrée à la pathologie, à la physiologie pulmonaire et à la biologie moléculaire, a mis au service de l’humanité plus de de 40 années de contributions à la compréhension des maladies pulmonaires. Il a sans aucun doute exercé une plus grande influence sur les connaissances pertinentes à la maladie pulmonaire obstructive chronique et à l’asthme au sein de la communauté médicale que toute autre personne dans le monde.

Le défi : Le système nerveux envoie des signaux à partir de notre cerveau à différentes parties de notre corps par l’intermédiaire de circuits. Cela nous permet de voir, de nous déplacer et de gérer nos pensées. Cependant, une paralysie accidentelle ou une maladie neurodégénérative vient perturber ces circuits. Le travail : Le Dr Jessell a découvert des voies génétiques et moléculaires conduisant au développement complexe de la moelle épinière. Cela améliore notre compréhension de la façon dont notre système nerveux communique.

Pourquoi cela est important : En comprenant comment les neurones sensoriels et les motoneurones communiquent, nous pouvons réparer les circuits endommagés et traiter ou guérir des lésions traumatiques causées par des maladies telles que la SLA, les accidents vasculaires cérébraux ou une blessure à la moelle épinière.

Tom Jessell était professeur Claire Tow aux départements de neurosciences, de biochimie et de biophysique moléculaire de l’Université Columbia. Il est ancien co-directeur du Kavli Institute for Brain Sciences et de la Mind Brain Behaviour Initiative.

De 1985 à 2018, Dr Jessell était le chercheur au Howard Hughes Medical Institute. Le Dr Jessell est membre de la Royal Society et de l’Académie britannique des sciences médicales, et il est associé étranger de l’Académie nationale des sciences et membre de l’Institut de médecine des États-Unis. En 2008, le Dr Jessell a été co-lauréat du Prix inaugural Kavli en neurosciences. Il a également reçu de nombreux autres prix.

† 1951-2019

Le défi : Comment notre horloge biologique interne guide-t-elle notre corps toute la journée? Le travail : Avec les Drs Michael Rosbash et Jeffrey Hall, le Dr Michael Young a découvert que nos horloges circadiennes sont contrôlées par un petit groupe de gènes qui travaillent au niveau de la cellule individuelle. Des mutations subtiles dans l’un de ces gènes peuvent accélérer ou ralentir nos rythmes quotidiens. Pourquoi cela est important : Leurs découvertes au sujet de l’horloge biologique ont des applications pour les troubles du sommeil et de l’appétit. Elles ont également des applications pour des organes tels que le cerveau, le foie, les poumons et la peau, qui utilisent les mêmes mécanismes génétiques pour contrôler leurs activités rythmiques. Le Dr Young a obtenu un doctorat en génétique de l’Université du Texas (1975). Il a fait un stage postdoctoral à l’Université Stanford avant de passer à l’Université Rockefeller. En 1991, il est devenu chef de l’unité du Science and Technology Center for Biological Timing, de la National Science Foundation, à l’Université Rockefeller. Il a été nommé vice-président des Affaires académiques (2004) et professeur Richard et Jeanne Fisher la même année. Son travail à l’Université Rockefeller a mis l’accent sur deux domaines : le développement neuromusculaire – découlant de l’isolement en laboratoire et de l’étude du locus Notch de la Drosophile – et la génétique du comportement, particulièrement les rythmes circadiens (y compris le clonage initial du gène de l’horloge biologique de la drosophile, la découverte et les caractérisations fonctionnelles des gènes de l’horloge circadienne intemporels, double-temps, ‘shaggy’, vrille et PDP1, et la modélisation des principales caractéristiques moléculaires du système circadien de la drosophile). Le Dr Young a été chercheur au Howard Hughes Medical Institute (1987 à 1996); il est membre de l’Académie nationale des sciences et de l’Académie américaine de microbiologie. Parmi les distinctions qu’a reçues le Dr Young, il y a le Prix en neuroscience 2009 de la Fondation Pierre et Patricia Gruber et le Prix Louisa Gross Horwitz de l’Université Columbia en 2011.

Le défi : La méningite, la pneumonie et le paludisme – tous dictés par le climat saisonnier – tuent des millions d’enfants dans le monde en développement chaque année. Le travail : Le paludisme est très répandu au cours de la saison des pluies. Le Dr Greenwood a démontré la valeur des moustiquaires de lit enduites d’insecticide et le traitement à l’aide de médicaments dans la prévention du paludisme. La pneumonie et la méningite sont plus répandues au cours de la saison sèche. Le Dr Greenwood a mis au point et testé deux groupes de vaccins contre ces infections, qui se sont révélés très efficaces pour sauver des vies d’enfants. Pourquoi cela est important : Le Dr Greenwood a été un promoteur infatigable de la santé des enfants dans les pays en développement en combattant la propagation de la maladie et en formant des scientifiques postdoctoraux en Afrique. Brian Greenwood a étudié la médecine à Cambridge (1962) et a poursuivi sa formation pendant trois ans dans l’Ouest du Nigeria, à l’Hôpital du Collège universitaire d’Ibadan. Après avoir acquis une formation complémentaire en immunologie clinique en Grande-Bretagne, il est retourné au Nigeria (1970) pour aider à établir une nouvelle école de médecine à l’Université Ahmadu Bello, à Zaria. Il a poursuivi ses recherches sur le paludisme et les maladies à méningocoques dans cet établissement. Le Dr Greenwood a dirigé pendant 15 ans le UK Medical Research Council Laboratories en Gambie (1980-1995). Il a aidé à établir un programme de recherche multidisciplinaire axé sur les maladies infectieuses les plus répandues : le paludisme, la pneumonie, la rougeole, la méningite, l’hépatite et le VIH2. Il a démontré l’efficacité des moustiquaires de lit imprégnées d’insecticide dans la prévention des décès dus au paludisme chez les enfants, ainsi que l’impact des vaccins Haemophilus influenzae de type b et antipneumococciques conjugués en Afrique subsaharienne. En 1996, le Dr Greenwood a rejoint la London School of Hygiene and Tropical Medicine, où il est maintenant professeur Manson de médecine tropicale clinique. Il a dirigé le Gates Malaria Partnership (2001-2009) et, en 2008, est devenu directeur du Malaria Capacity Development Consortium, qui appuie les programmes de formation de lutte contre le paludisme dans cinq universités d’Afrique subsaharienne. Il est également directeur d’un consortium qui étudie l’épidémiologie de l’infection à méningocoques en Afrique avant l’introduction d’un nouveau vaccin conjugué.

Le défi : Comment notre horloge biologique interne guide-t-elle notre corps toute la journée? Le travail : Avec les Drs Jeffrey Hall et Michael Young, le Dr Rosbash a découvert que nos horloges circadiennes sont contrôlées par un petit groupe de gènes qui travaillent au niveau de la cellule individuelle. Des mutations subtiles dans l’un de ces gènes peuvent accélérer ou ralentir nos rythmes quotidiens. Pourquoi cela est important : Leurs découvertes au sujet de l’horloge biologique ont des applications pour les troubles du sommeil et de l’appétit. Elles ont également des applications pour des organes tels que le cerveau, le foie, les poumons et la peau, qui utilisent les mêmes mécanismes génétiques pour contrôler leurs activités rythmiques. Michael Rosbash, Ph.D., est chercheur au Howard Hughes Medical Institute et professeur de biologie à l’Université Brandeis, à Waltham, au Massachusetts. Michael Rosbash a contribué à révéler la base moléculaire des rythmes circadiens, l’horloge biologique intégrée qui régit le sommeil et l’éveil, l’activité et le repos, les niveaux d’hormones, la température du corps et d’autres fonctions. À l’aide de la mouche à fruit drosophile, il a identifié des gènes et des protéines impliquées dans la régulation de cette horloge et a proposé une théorie de son fonctionnement. Les découvertes de Michael Rosbash s’appliquent aux humains et à d’autres mammifères et pourraient éventuellement conduire à la mise au point de médicaments pour traiter l’insomnie, le décalage horaire et d’autres troubles du sommeil. Après son arrivée à l’Université Brandeis, Michael Rosbash s’est de plus en plus intéressé à l’influence des gènes sur le comportement. En 1974, il a commencé à travailler avec Jeffrey Hall et, en 1984, ils ont cloné le gène de l’horloge interne. Plusieurs années plus tard, ils ont proposé un mécanisme par lequel une horloge moléculaire de 24 heures pourrait fonctionner : une boucle de rétroaction négative transcriptionnelle. Leur modèle tient toujours, en dépit de la découverte de gènes supplémentaires du rythme circadien. En substance, les gènes qui font partie de cette boucle activent la production de protéines clés jusqu’à ce qu’une activité critique de chacune s’accumule et désactive la transcription.

Le défi : Comment les cellules savent-elles quels gènes utiliser et lesquels ignorer? Le travail : Howard Cedar – avec Aharon Razin et Adrian Bird – a démontré comment l’ajout d’un groupe chimique simple (un groupe méthyle) à l’ADN affecte le moment et la façon dont l’information génétique est utilisée. Pourquoi cela est important : Comprendre comment activer et désactiver la méthylation pourrait conduire à des traitements pour le cancer et d’autres maladies. Biographie Le professeur Howard Cedar est né à New York en 1943. Il a obtenu un B.Sc. en mathématiques du M.I.T. et a ensuite poursuivi des études de médecine et un doctorat en microbiologie sous la tutelle du Dr James Schwartz à l’Université de New York (N.Y.U.), recevant son diplôme en 1970. Il a effectué des recherches postdoctorales avec le Dr Eric Kandel à NYU et, par la suite, avec le Dr Gary Felsenfeld aux NIH au sein du Service de santé publique. En 1973, il a émigré en Israël où il s’est joint au corps professoral de l’Université hébraïque, devenant professeur titulaire en 1981. Le professeur Cedar est récipiendaire du Prix Hestrin de biochimie (1979) et d’une bourse de chercheur exceptionnel de l’Université hébraïque (1991), Il a été élu à l’EMBO en 1982, a reçu le Prix d’Israël en 1999 et est devenu membre de l’Académie israélienne des sciences en 2003. Il a reçu le prix Wolf en médecine en 2008 et le Prix Emet en sciences de la vie en 2009. Trois de ses élèves ont remporté indépendamment le prestigieux prix GE-Sciences pour le meilleur travail de doctorat à travers le monde.

Le défi : Trouver un traitement efficace pour les maladies diarrhéiques, qui entraînent le décès de 1,3 million d’enfants chaque année. Le travail : Grâce à l’étude de l’interaction des maladies infectieuses et de la nutrition, le Dr Black a découvert que l’adoption d’une formule de reconstitution du zinc pourrait permettre à la fois de traiter et de prévenir la diarrhée. Pourquoi cela est important : La reconstitution du zinc pour contrer la diarrhée infantile est maintenant le traitement normalisé recommandé par l’OMS et l’UNICEF. Robert E. Black, M.D., M.P.H., est professeur Edgar Berman et président du Département de santé internationale et directeur de l’Institut des programmes internationaux de l’École de santé publique Johns Hopkins Bloomberg à Baltimore, au Maryland. Il a acquis une formation en médecine axée sur les maladies infectieuses et l’épidémiologie, et il a servi comme médecin épidémiologiste au Centers for Disease Control. Le Dr Black a travaillé dans des établissements au Bangladesh et au Pérou, effectuant de la recherche sur les maladies infectieuses infantiles et les problèmes nutritionnels. Les recherches actuelles du Dr Black comprennent des essais sur le terrain portant sur des vaccins, des micronutriments et d’autres interventions nutritionnelles, des études sur l’efficacité des programmes de santé (tels que la gestion intégrée de l’approche des maladies de la petite enfance) et l’évaluation des programmes de services de santé préventifs et curatifs dans les pays à revenu faible ou intermédiaire. Il s’intéresse également à l’utilisation de données probantes dans les politiques et les programmes, y compris les estimations du fardeau de la maladie, le développement des capacités de recherche et le renforcement de la formation en santé publique. À titre de membre de l’Institut de médecine, d’organes consultatifs de l’Organisation mondiale de la Santé, et de l’Institut international de recherche sur les vaccins, entre autres, le Dr Black participe à l’élaboration de politiques visant à améliorer la santé des enfants. Il préside actuellement le Groupe de référence sur l’épidémiologie de la santé de l’enfant et l’Initiative de recherche sur la nutrition et la santé des enfants. Il dirige des projets au Bangladesh, au Bénin, au Ghana, en Inde, au Mali, au Pakistan, au Pérou, au Sénégal, à Zanzibar et au Zimbabwe. Il a contribué à plus de 450 articles parus dans revues scientifiques et a co-rédigé l’ouvrage « International Public Health ».

Le défi : Pour savoir ce qu’elle est la réponse immunitaire naturelle reconnaissant les bactéries et les virus étrangers. Le travail : Les récepteurs ressemblant aux Toll présents dans les cellules de l’organisme détectent les microbes et mobilisent le système immunitaire afin de combattre l’infection et développer une immunité à long terme. Pourquoi cela est important : Le travail conduit à la mise au point de médicaments et de thérapies pour le cancer, les allergies, les maladies auto-immunes et le choc septique. Biographie Jules Hoffmann est né au Luxembourg et a obtenu un doctorat en biologie (1969) de l’Université de Strasbourg. Il a occupé divers postes au sein de l’Agence nationale française de recherche (CNRS), et plus récemment celui de directeur de recherche émérite et membre du conseil d’administration. Il est aussi professeur invité à l’Université de Strasbourg. Il a été directeur de l’Institut de biologie moléculaire et cellulaire du CNRS à Strasbourg (1993-2005). La recherche du Dr Hoffmann a porté sur le développement et les réactions de défense des insectes. Depuis 1990, lui et son laboratoire ont exploré les mécanismes antimicrobiens puissants de la drosophile comme paradigme des défenses immunitaires innées. En particulier, le groupe est réputé avoir décrypté le rôle des récepteurs Toll dans la lutte contre les infections. Membre de l’Académie nationale des sciences de France, le Dr Hoffmann a servi comme président en 2007-2008. Il est membre de l’Organisation européenne de biologie moléculaire (EMBO) et de l’Académie nationale des sciences Leopoldina d’Allemagne. Le Dr Hoffmann est associé étranger de l’Académie nationale des sciences des États-Unis, de l’Académie américaine des arts et des sciences et de l’Académie des sciences de Russie. Il est récipiendaire du Prix Alexander von Humbold, du Prix William B. Coley, du Prix Robert Koch, du Prix Balzan, du Prix Lewis Rosenstiel et du Prix Keio en sciences médicales.

Le défi : Pour savoir ce que la réponse immunitaire naturelle est qui reconnaît les bactéries et les virus étrangers. Le travail : Des récepteurs ressemblant aux Toll présents dans les cellules de l’organisme détectent les microbes et mobilisent le système immunitaire afin de combattre l’infection et de développer une immunité à long terme. Pourquoi cela est important : Le travail conduit à la mise au point de médicaments et de thérapies pour le cancer, les allergies, les maladies auto-immunes et le choc septique. Biographie Shizuo Akira a reçu un diplôme de médecine de l’Université d’Osaka en 1977. Après une formation clinique de trois ans, il est entré à l’École supérieure de médecine de l’Université d’Osaka, où il a obtenu un doctorat en 1984. Il a passé deux ans (1985-1987) comme stagiaire postdoctoral au Département de microbiologie et d’immunologie de l’Université de la Californie à Berkeley. Il a été associé de recherche (1987-1995) à l’Institut de biologie moléculaire et cellulaire de l’Université d’Osaka dans le laboratoire du Dr Tadamitsu Kishimoto, où il a cloné deux facteurs de transcription NF-IL6 (C/EBPbeta) et STAT3. En 1996, le Dr Akira est devenu professeur au Département de biochimie du Collège de médecine Hyogo. En 1999, il a été nommé professeur à l’Institut de recherche sur les maladies microbiennes de l’Université d’Osaka. Depuis 2007, il est directeur du WPI Immunology Frontier Research Center, à l’Université d’Osaka. Le Dr Akira est membre de l’Académie nationale des sciences et de l’Organisation européenne de biologie moléculaire (EMBO). Il a reçu un certain nombre de prix prestigieux, dont le Prix Robert Koch, le Prix William B. Coley et le Prix Keio en science médicale internationale.

The challenge: How do cells know which genes to use and which to ignore?

The work: Bird – along with Aharon Razin and Howard Cedar – demonstrated how adding a simple chemical group (a methyl group) to DNA affects how and when genetic information is used.
Why it matters: Understanding how to turn methylation on and off could lead to treatments for cancer and other diseases.
Bio
Adrian Bird holds the Buchanan Chair of Genetics at the University of Edinburgh and is Director of the Wellcome Trust Centre for Cell Biology. He obtained his PhD at Edinburgh University. Following postdoctoral experience at the Universities of Yale and Zurich, he joined the Medical Research Council's Mammalian Genome Unit in Edinburgh. In 1987 he moved to Vienna to become a Senior Scientist at the newly-founded Institute for Molecular Pathology. Dr Bird's research focuses on the basic biology and biomedical significance of DNA methylation. His laboratory identified CpG islands as gene markers in the vertebrate genome and discovered proteins that read the DNA methylation signal to influence chromatin structure. Mutations in one of these proteins, MeCP2, cause the autism spectrum disorder Rett Syndrome. Dr Bird's laboratory established a mouse model of Rett Syndrome and showed that the resulting severe neurological phenotype can be cured. Awards include the Louis-Jeantet Prize for Medicine (1999) and the Charles-Léopold Mayer Prize of the French Academy of Sciences (2008). He was a governor of the Wellcome Trust from 2000 - 2010 and is currently a Trustee of Cancer Research UK.

The challenge: Treating patients who have rare genetic diseases such as Huntington’s and lipid diseases.
The work: Hayden defined the mechanisms that underlie 10 genetic diseases and developed applicable treatments. He also created a network of research, clinical trials and companies now working on effective products.
Why it matters: Hayden’s leadership has had a profound impact on science in Canada and abroad and has generated hope in the effective treatment of genetic diseases.

Bio
Michael Hayden MB (1975) PhD (1979), University of Cape Town, did post-doctoral work and training in Internal Medicine at Harvard Medical School. His research focuses on genetic diseases, including genetics of lipoprotein disorders, Huntington’s disease, and predictive and personalized medicine. He is co-leader of the Canadian Pharmacogenomics Network for Drug Safety project. Honours include the Order of Canada, Jacob Biely Prize, Prix Galien, and Order of British Columbia. In 2008 he was named CIHR’s Health Researcher of the Year. He was awarded the Leadership and Research Excellence Award by the National Centres of Excellence and the Lifetime Achievement Award by the Huntington Society of Canada (2001).

Dr. Hayden has founded three successful biotechnology companies and, in 2006, received 5 different entrepreneurial awards.

Dr. Hayden has initiated, and leads, an international effort to bring benefit to a community living with HIV/AIDS in South Africa. It aims to promote responsible sexual behaviors among at-risk youth, empower HIV/AIDS-affected youth, and build a sense of self and community participation.

William G. Kaelin Jr. est professeur au Département de médecine du Dana-Farber Cancer Center et au Brigham and Women’s Hospital, de l’École de médecine de l’Université Harvard, où il est directeur associé des sciences fondamentales pour le Dana-Farber/Harvard Cancer Center. Il a obtenu un baccalauréat et un diplôme de médecine de l’Université Duke et a complété sa formation en médecine interne à l’Hôpital Johns Hopkins, où il a été chef résident en médecine. Il a été chercheur-clinicien en oncologie médicale au Dana-Farber Cancer Institute et, subséquemment, stagiaire postdoctoral dans le laboratoire de David Livingston, alors qu’il était chercheur boursier McDonnell. Le Dr Kaelin est membre de l’American Society for Clinical Investigation et de l’American College of Physicians. Il a récemment siégé au National Cancer Institute Board of Scientific Advisors, au conseil de direction de l’AACR, et à l’Institute of Medicine National Cancer Policy Board. Il est récipiendaire du Prix Paul Marks pour la recherche sur le cancer remis par le Memorial Sloan-Kettering Cancer Center, du Prix Richard et Hinda Rosenthal de l’AACR, et du Prix Doris Duke de scientifique clinique chevronné. En 2007, il a été élu à l’Institut de médecine. Chercheur au Howard Hughes Medical Center depuis 1998, les recherches du Dr Kaelin visent à comprendre comment, sur le plan mécanique, les mutations affectant les gènes suppresseurs de tumeurs sont une cause de cancer. Son laboratoire se concentre actuellement sur l’étude des gènes VHL, RB-1 et p53, suppresseurs de tumeurs. Son objectif à long terme est d’établir les fondements de nouvelles thérapies anticancéreuses reposant sur les fonctions biochimiques de ces protéines. Ses travaux sur la protéine VHL ont aidé à susciter les essais cliniques, éventuellement couronnés de succès, sur les inhibiteurs du VEGF dans le traitement du cancer du rein. En outre, cette voie de recherche a ouvert de nouvelles perspectives sur la façon dont les cellules détectent et réagissent aux changements dans l’oxygène, ce qui a des conséquences pour les maladies autres que le cancer, telles que l’anémie, l’infarctus du myocarde et les accidents vasculaires cérébraux.

Le Dr Stiller est professeur émérite au Département de médecine et au Département de microbiologie et d’immunologie de l’Université Western Ontario. Il a créé le Service de transplantation d’organes multiples à London, en Ontario, et a été chef de cette unité jusqu’en 1996. Au cours de cette période, il a été chercheur principal au sein de l’étude multicentrique canadienne qui a établi l’importance de la cyclosporine dans la transplantation et conduit à son utilisation dans le monde entier comme thérapie de première ligne lors du rejet d’une greffe. Il fut le premier à démontrer l’efficacité de l’immunosuppression dans le diabète de type 1 nouvellement diagnostiqué, établissant que cette maladie humaine constitue un trouble immunitaire. Il a publié plus de 250 articles scientifiques. Le Dr Stiller est co-fondateur de deux fonds en soins de santé, dont le Fonds de découvertes médicales canadiennes Inc., où il a servi à titre de président du conseil et chef de la direction. Il a été membre du conseil et du comité exécutif du Conseil de recherches médicales du Canada (1987-1993), président fondateur du Fonds ontarien d'encouragement à la recherche-développement, et président du conseil (co-fondateur) de l’Institut ontarien de recherche sur le cancer et du Fonds ontarien pour l'innovation. Le Dr Stiller est membre du conseil d’administration de plusieurs entreprises publiques et fondations, et il est co-fondateur et directeur du MaRS Discovery District. Il est également récipiendaire de nombreux prix dont le Prix MEDEC (1992), l’Ordre du Canada (1995) et de l’Ordre de l’Ontario (2000). Il a reçu trois doctorats honorifiques – de l’Université McMaster, de l’Université de la Saskatchewan et de l’Université Western. Il a été intronisé au Temple de la renommée médicale canadienne en 2010.

Le Dr Pierre Chambon est professeur honoraire au Collège de France (Paris) et professeur émérite à la Faculté de médecine de l’Université de Strasbourg. Il a été le fondateur et ancien directeur de l’IGBMC et, aussi, le fondateur et ancien directeur de l’Institut clinique de la souris (ICS/MCI), à Strasbourg. Le Dr Chambon est un expert mondial dans les domaines de la structure des gènes et du contrôle transcriptionnel de l’expression génique. Au cours des 25 dernières années, ses études sur la structure et la fonction des récepteurs nucléaires ont changé notre conception de la transduction du signal et de l’endocrinologie. En clonant les récepteurs de l’œstrogène et de la progestérone, et en découvrant la famille des récepteurs de l’acide rétinoïque, il a largement contribué à la découverte de la superfamille des récepteurs nucléaires et à l’élucidation de leur mécanisme d’action universel, qui relie la transcription, la physiologie et la pathologie. Au fil de ses études poussées sur la mutagenèse dirigée et la génétique chez la souris, Pierre Chambon a dévoilé l’importance primordiale de la signalisation des récepteurs nucléaires dans le développement embryonnaire et l’homéostasie au stade adulte. Les découvertes de Pierre Chambon ont révolutionné les domaines du développement, de l’endocrinologie et du métabolisme, et leurs troubles, pointant vers de nouvelles méthodes de découverte de médicaments et trouvant des applications importantes en biotechnologie et en médecine moderne. Ces réalisations scientifiques sont logiquement inscrites dans une série ininterrompue de découvertes faites par Pierre Chambon durant les 45 dernières années dans le domaine du contrôle transcriptionnel de l’expression génique chez les eucaryotes supérieurs : la découverte de la PolyADPribose (1963), la découverte de plusieurs ARN polymérases différemment sensibles à l’a-amanitine (1969), la contribution à l’élucidation de la structure de la chromatine – le nucléosome (1974), la découverte de gènes divisés chez les animaux (1977), la découverte d’éléments amplificateurs (1981) et la découverte d’éléments promoteurs multiples et de leurs facteurs apparentés (1980 à 1993). Le Dr Pierre Chambon a reçu de nombreux prix internationaux, dont le Prix Lasker en recherche médicale fondamentale 2004 pour la découverte de la superfamille des récepteurs nucléaires hormonaux et l’élucidation d’un mécanisme unificateur qui régule le développement embryonnaire et diverses voies métaboliques. Il est membre de l’Académie française des sciences et, également, membre étranger de l’Académie nationale des sciences des États-Unis et de l’Académie royale suédoise des sciences. Pierre Chambon siège à divers comités de rédaction, dont ceux des revues Cell et Molecular Cell. Il est l’auteur de plus de 900 publications. Il a été classé au quatrième rang des plus éminents spécialistes des sciences de la vie pour la période 1983-2002.

Natif du Rhode Island, le Dr William A. Catterall a reçu un baccalauréat en chimie de l’Université Brown en 1968 et un doctorat en chimie physiologique de l’École de médecine de l’Université Johns Hopkins en 1972, et il a effectué sa formation postdoctorale en neurobiologie et en pharmacologie moléculaire comme chercheur à l’Association de la dystrophie musculaire auprès du Dr Marshall Nirenberg aux National Instituts of Health de 1972 à 1974. Après trois autres années passées comme chercheur aux National Institutes of Health, il s’est joint au corps professoral de l’École de médecine de l’Université de Washington en 1977, où il est devenu professeur agrégé au Département de pharmacologie, puis professeur titulaire en 1981 et président du Département en 1984. Après avoir établi son laboratoire à l’Université de Washington, le Dr Catterall et ses collègues ont découvert les protéines sodiques et calciques sensibles au voltage, responsables de la production des signaux électriques dans le cerveau, le cœur, les muscles squelettiques et d’autres cellules excitables. Leurs travaux ultérieurs ont beaucoup contribué à la compréhension de la structure, de la fonction, de la régulation et de la pharmacologie moléculaire de ces molécules clés de signalisation cellulaire. Les récents travaux du docteur Catterall ont porté sur la compréhension des maladies causées par l’altération de la fonction et de la régulation des canaux ioniques sensibles au voltage, y compris l’épilepsie et la paralysie périodique. Les premières recherches du Dr Catterall ont été reconnues par l’octroi du Prix de jeune scientifique de la Fondation Passano, en 1981, et du Prix Jacob Javits de chercheur en neurosciences, en 1984 et 1991. Le Dr Catterall a reçu le Prix en science fondamentale de l’American Heart Association en 1992, le Prix Mathilde Solowey en neurosciences des National Institutes of Health, le Prix H.B. Van Dyke en pharmacologie de l’Université Columbia en 1995, le Prix de chercheur principal en neurosciences de la Fondation McKnight en 1998, et le Prix Bristol-Myers Squibb pour ses réalisations exceptionnelles en recherche neuroscientifique en 2003. Le Dr Catterall a été élu à l’Académie nationale des sciences en 1989, où il a servi comme président de la Section de physiologie et de pharmacologie de 1998 à 2001. Il a été élu à l’Institut de médecine et à l’Académie des arts et des sciences des États-Unis en 2000, et a été élu membre étranger de la Royal Society de Londres en 2008. Il a été rédacteur en chef de Molecular Pharmacology de 1985 à 1990, membre fondateur du comité de rédaction de Neuron en 1988 et membre du comité de rédaction de nombreuses autres revues professionnelles. Le Dr Catterall et ses collègues ont publié plus de 400 articles scientifiques et 30 critiques et textes de référence sur les canaux ioniques sensibles au voltage.

Le Dr Semenza a reçu sa formation de premier cycle (A.B.) en biologie à l’Université Harvard; il a ensuite obtenu un diplôme de médecine et un doctorat de l’Université de Pennsylvanie; Il a ensuite poursuivi une formation de résident en pédiatrie au Centre médical de l’Université Duke et une formation postdoctorale en génétique médicale à l’École de médecine de l’Université Johns Hopkins, où il a passé toute sa carrière. Il est actuellement professeur C. Michael Armstrong à l’université Johns Hopkins comportant des affectations en pédiatrie, en médecine, en oncologie, en radio-oncologie et en chimie biologique, ainsi qu’à l’Institut McKusick-Nathans de médecine génétique. Depuis 2003, il a été directeur-fondateur du Programme vasculaire au Johns Hopkins Institute for Cell Engineering. Le laboratoire du Dr Semenza a identifié le facteur 1 (HIF-1) inductible par hypoxie, un facteur de transcription qui permet aux cellules de réagir aux changements dans la disponibilité de l’oxygène. La purification du HIF-1 et l’identification de ses séquences codantes en 1995 ont ouvert le champ de la biologie de l’oxygène à l’analyse moléculaire et révélé des rôles importants pour le facteur HIF-1 dans de nombreux processus développementaux, physiologiques et pathologiques, y compris les maladies cardiovasculaires et le cancer. Le Dr Semenza est membre du comité de rédaction des revues Antioxidants and Redox Signaling, Cancer Research, Cardiovascular Research, Circulation Research, Experimental Physiology, Journal of Clinical Investigation, Molecular and Cellular Biology, Molecular Cancer Therapeutics, et Oncogene. Il est rédacteur en chef du Journal of Molecular Medicine. Il a été élu membre de la Society for Pediatric Research, de l’American Society for Clinical Investigation, de l’Association of American Physicians et de l’Académie nationale des sciences des États-Unis.

Peter J. Ratcliffe a fréquenté l’école Lancaster Royal Grammar, où il a obtenu une bourse ouverte pour étudier au Collège Gonville and Caius, à Cambridge, en 1972. Il a fait son cours de médecine à Cambridge et à l’hôpital St. Bartholomew de Londres, obtenant son diplôme avec distinction en 1978. Il s’est spécialisé en médecine rénale à Oxford, travaillant d’abord sur la physiologie de l’oxygénation rénale et ses conséquences pour les lésions rénales en état de choc. En 1989, après avoir obtenu une bourse de chercheur principal du Wellcome Trust, il a changé de domaine pour fonder un nouveau laboratoire travaillant sur les voies de détection de l’oxygène au niveau cellulaire. Pendant plus de 20 ans, il a dirigé le groupe ‘de détection de l’oxygène’ successivement à l’Institut Weatherall de médecine moléculaire, au Centre Henry Wellcome de médecine génomique, et au Centre Henry Wellcome de physiologie moléculaire, à l’Université d’Oxford. Il a été nommé enseignant universitaire en 1992, et professeur titulaire en 1996. Il a été élu Professeur Nuffield de médecine en 2003, et nommé chef du Département de médecine en 2004. Les distinctions qu’il a reçues comprennent le Prix de la Fondation Milne-Muerke en 1991, le Prix Bull Graham en 1998, le Prix de l’International Society for Blood Purification en 2002 et le Prix Louis Jeantet de médecine en 2009. Il a été élu membre de l’Académie des sciences médicales et membre de la Royal Society en 2002; il a également été nommé au sein du EMBO en 2006 et membre étranger honoraire de l’Académie américaine des arts et des sciences en 2007.

The Work:
Dr. Endo discovered the first statin drug, compactin, and demonstrated its clinical efficacy. Statins are a class of drugs with remarkable cholesterol-lowering properties that have revolutionized the prevention and treatment of coronary heart disease (CHD). They lower the part of cholesterol known as “bad cholesterol”, technically known as low density lipoprotein or LDL cholesterol. Dr. Endo sifted through thousands of organisms, hunting for natural substances(products) that block a key enzyme in the biochemical pathway that produces cholesterol, a major contributor to CHD. The organism he found does exactly that and his work stimulated Merck to launch a drug-development program that led, 20+ years ago, to the first statin approved for medical use. This advance paved a path for other pharmaceutical companies to follow.

The Impact:
Statins are now routinely used to prevent and treat CHD throughout the world. Although CHD is aggravated by multiple risk factors, reducing LDL levels alone makes a significant impact. By discovering statins, Dr. Endo ushered in a new era in preventing and treating CHD and it is estimated that millions of people have extended their lives through statin therapy.

Les travaux:

Le Dr Hakim est l’un des plus éminents scientifiques du Canada et il a acquis une renommée mondiale par son leadership en recherche neuroscientifique, ciblant ses efforts sur les AVC. Au début des années 1980, le Dr Hakim à caractérisé une région pénombrale autour du noyau ischémique d’un AVC – du tissu cervical ayant assez d’énergie pour survivre durant une courte période après la perte de sang et ayant la possibilité de retrouver une fonction normale si la circulation sanguine est rétablie. Le Dr Hakim, qui s’est joint à l’Université d’Ottawa en 1992, a été l’origine de la création d’un Réseau de Centres d’excellence, le Réseau canadien contre les accidents cérébrovasculaires; il s’est ensuite associé avec la Fondation des maladies du cœur et d’autres organisations pour élaborer et mettre en œuvre à l’échelle nationale la Stratégie canadienne de l’AVC. Ce travail a été essentiel à l’évolution des attitudes envers les accidents vasculaires cérébraux, qui est passée d’une affection dévastatrice à une maladie évitable, traitable et réparable.

L’impact:

En 2006, le Dr Hakim et ses collègues ont publié la première « Recommandations canadiennes pour les pratiques optimales de soins de l'AVC » (mise à jour en 2008, 2010 et 2012) et élaboré des indicateurs de performance et des trousses à l’intention des fournisseurs de soins de santé en vue de mettre en place des unités d’AVC et d’améliorer les services médicaux d’urgence. Ils ont également institué un programme national d’éducation à plusieurs volets pour améliorer la prévention des accidents vasculaires cérébraux et la prestation des soins aux patients atteints d’un AVC aigu grâce à la coordination des services et à l’application de pratiques optimales. Dans les cinq ans de la mise en œuvre de cette stratégie, en Ontario seulement, les renvois aux cliniques de prévention des AVC ont augmenté de 34 % tandis que les admissions de patients victimes d’un AVC ont diminuaient de 11 %.

The Work:

Dr. Hakim is one of Canada’s most distinguished scientists who has earned a world-renowned reputation for his leadership in neuroscience research with an emphasis on stroke research. In the early 1980's Dr. Hakim characterized a penumbral region around a stroke’s ischemic core — brain tissue with enough energy to survive for a short time after blood loss and with the potential to regain normal function if blood flow was restored. Dr. Hakim, who joined the University of Ottawa in 1992, led the charge to set up the Canadian Stroke Network, a network of centres of excellence; he then partnered with the Heart and Stroke Foundation and other organizations to develop and apply a nation-wide Canadian Stroke Strategy. This work was critical to changing attitudes towards strokes, which went from being a devastating condition to one that is preventable, treatable and repairable.

The Impact:

In 2006, Dr. Hakim and colleagues published the first ‘Canadian Best Practice Recommendation for Stroke Care’ (updated in 2008, 2010 and 2012) and developed performance indicators and toolkits for healthcare providers to set up stroke units and improve emergency medical services. They also instituted a multi-layered national education program to enhance stroke prevention and the delivery of acute stroke care through the coordination of services and the implementation of best practices. Within five years of the Strategy’s implementation, Ontario alone saw referrals to stroke prevention clinics increase by 34% and stroke patient admissions decrease by 11%.

The work:

Dr. Victora’s career has focused on the factors affecting maternal and child health in low- and middle income countries. He has concentrated in the three main areas of child health and nutrition, health program monitoring and evaluation, and health equity. Returning to Brazil after his doctorate, he helped set up one of the longest running birth cohort studies in the world, the 1982 Pelotas Birth Cohort, in which 6,000 individuals are being followed up to the present time. His studies helped establish the influence of the first 1,000 days (from conception until the age of two years) on lifelong outcomes, including chronic diseases and human capital.

The Impact:

Possibly, Dr. Victora’s greatest contribution to Public Health was his work in the 1980s with the first study showing the importance of exclusive breastfeeding for preventing infant mortality. His findings contributed to global policy recommendations by UNICEF and the World Health Organization for mothers to breastfeed their infants exclusively for the first six months of life. More recently, his long-term birth cohorts documented the benefits of breastfeeding for adult intelligence, education and income, as well as the long-term consequences of early-life undernutrition. Dr. Victora also made important contributions on how to evaluate the impact of health programs on child mortality and on the study of social inequalities in child health.

The work:
Dr. Rappuoli is a pioneer in the world of vaccines and has introduced several novel scientific concepts. First, he introduced the concept that bacterial toxins can be detoxified by manipulation of their genes (genetic detoxification, 1987). Next, the concept that microbes are better studied in the context of the cells they interact with (cellular microbiology, 1996), and then the use of genomes to develop new vaccines (reverse vaccinology, 2000). In the process of reverse vaccinology the entire genomic sequence of a pathogen is screened using bioinformatics tools to help determine which genes code for which proteins, against which vaccines can be developed.

The impact:
Dr. Rappuoli also worked on several molecules which became part of licensed vaccines. He characterized a molecule, CRM197, that today is the most widely used carrier for vaccines against Haemophilus influenzae, meningococcus and pneumococcus. Later he developed a vaccine against pertussis containing genetically detoxified pertussis toxin and the first conjugate vaccine against meningococcus C that eliminated the disease in the United Kingdom in 2000. His work on reverse vaccinology led to the licensure of the first meningococcus B vaccine approved in Europe and Canada in 2013 and USA in 2015.

The Work:
Professor Kay and his coworkers have made important contributions to the field of biomolecular nuclear magnetic resonance (NMR) spectroscopy, with the development of methods that are used to ‘visualize’ protein molecules in their natural solution environment and to obtain information about how their shapes evolve in time, leading to biological function. These methods have shed light on how molecules involved in neurodegeneration can form abnormal structures that ultimately lead to diseased states. In addition, his work has extended our understanding of how cellular machines function and how the communication between different parts of these machines can be targeted for the development of drugs in the fight against certain cancers.

The Impact:
His research has expanded our understanding of the flexible nature of protein structure and the importance of flexibility to both function and malfunction. This, in turn, has led to new insights into what the key regions of molecules might be for drug targeting. The methods developed by Dr. Kay are used in labs around the world, including those researching illnesses such as diabetes, cancer and cardiovascular disease. The tools developed by his research group are disseminated freely and are extensively used worldwide.

The Work:
Trained as a child neurologist, Zoghbi could not bear the plight of children affected by devastating neurological diseases so she pursued research in hope of helping her patients. After encounters with patients with Rett syndrome—a disorder that strikes after a year of normal development and presents with developmental regression, social withdrawal, loss of hand use and compulsive wringing of the hands, seizures and a variety of neurobehavioral symptoms—she decided to find its genetic roots. The biggest challenge was that Rett syndrome is typically a sporadic disorder (one in a family) and the genome was neither mapped nor sequenced. Zoghbi’s perseverance paid off when after a 16-year search she discovered that Rett syndrome is caused by mutations in MECP2. Zoghbi revealed the importance of MeCP2 for the function of various neuronal subtypes and pinpointed the contributions of various neuronal subtypes in the brain to various neuropsychiatric features. Zoghbi also provided evidence that the brain is exquisitely sensitive to the levels of MeCP2 and that doubling MeCP2 levels causes progressive neurological deficits in mice. This disorder is now recognized as MECP2 Duplication Syndrome in humans. Her recent work showed the symptoms of adult mice modeling the duplication disorder can be reversed using antisense oligonucleotides that normalize MeCP2 levels.

The Impact:
The discovery of the Rett syndrome gene provided a straightforward diagnostic genetic test allowing early and accurate diagnosis of the syndrome. It also revealed that mutations in MECP2 can also cause a host of other neuropsychiatric features ranging from autism to juvenile onset schizophrenia. Further, it provided evidence that an autism spectrum disorder (ASD) or an intellectual disability disorder (IDDs) can be genetic even if it is sporadic (not inherited). Today we know that dozens of ASDs and IDDs are caused by sporadic new mutations. Moreover, her discovery opened up a new area of research on the role of epigenetics in neuropsychiatric phenotypes. Her use of an antisense oligonucleotide to lower MeCP2 levels provides a potential therapeutic strategy for the MECP2 duplication syndrome and inspires similar studies for other duplication disorders.

The Work:

Dr. Julius has used distinctive molecules from the natural world – including toxins from tarantulas and coral snakes, and capsaicin, the molecule that produces the “heat” in chili peppers – to understand how signals responsible for temperature and pain sensation are transmitted by neural circuits to the brain.

In his research Dr. Julius has homed in on a class of proteins called TRP (pronounced “trip”) ion channels to discover how the chemical compound responsible for the spicy heat of chili peppers – called capsaicin – elicits a burning sensation when eaten or touched. The research led to the identification and cloning of the specific protein responsible, named TRPV1. On the flip side, Dr. Julius has used menthol, a natural cooling agent, to identify a receptor for “real” cold. This protein, named TRPM8, is a close molecular cousin of TRPV1, pointing to a common mechanism for sensing temperature. As in the case of TRPV1, this ion channel contributes to hypersensitivity to cold, such as that experienced after chemotherapy or other types of nerve injury.

The Impact:

Somatosensation, our sense of touch and pain, serves as a warning system to guard us against injury. While critical to our survival and well-being, this system can become hypersensitive, resulting in chronic pain. This work helps to explain how such positive and negative aspects of pain sensation arise – insight that is critical to understanding the genesis of chronic pain syndromes. One indication of the importance of this work to medicine is the interest in TRP channels as potential targets for a new generation of painkillers.

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Dr. Benzer's work in the 1950's, which was recognized by a Gairdner Award in 1964, achieved the fine-structure mapping of a gene, thereby laying the foundations of molecular genetics. His later studies, recognized by the 2004 Gairdner Award, tackled the problem of the inheritance of behavior, using gene mutations to dissect the underlying events in the nervous system of the fruit fly, Drosophila. His work led to the discovery of specific genes that participate in various behavioral phenomena, including genes such as per, which controls the biological clock, dunce, which is needed for learning, and other genes, shown to be important for sexual courtship, vision, or prevention of neurodegeneration. At age 82, Benzer continues to do pioneering research that focuses on the problem of aging, with Drosophila as a model organism.

Dr. Seymour Benzer is the Boswell Professor of Neuroscience, Emeritus (Active) at the California Institute of Technology (Caltech), in Pasadena, California. Benzer grew up in Brooklyn, New York, and majored in physics at Brooklyn College. Graduating in 1942, he continued his studies at the Purdue University, Lafayette, Indiana, where he participated in the war effort to develop semiconductor devices for detecting radar microwaves. On receiving his PhD in 1947, he was appointed to the faculty at Purdue, but, inspired by reading Schrodinger's book "What is Life", soon requested leave of absence to study genes, spending two years with Max Delbruck at Caltech and a year at the Pasteur Institute with Jacob, Monod, and Lwoff. Benzer moved his laboratory from Purdue University to Caltech in 1965. He received The Lasker Award in 1971, International Academy of Sciences in 1975 and 2001 and the Wolf Prize for Medicine in 1991.

He also received the Canada Gairdner International Award in 2004 for pioneering discoveries that both founded and greatly advanced an entire field of neurogenetics, thereby transforming our understanding of the brain and its mechanisms.

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Frederick Sanger also received the Canada Gairdner International Award in 1971 for his contributions to the study of the structure of complex biochemical substances, and in particular for determining the precise chemical composition of insulin.

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Sydney Brenner also received the Canada Gairdner International Award in 1991 for establishing C. elegans as a model for studying the genetic control of development.

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Oliver Smithies also received the Canada Gairdner International Award in 1993 for pioneering work in the use of homologous recombination to generate targeted mutations in the mouse.

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† 1952-2016

† 1925-2013

Janet Davidson Rowley was born in New York City. She received her BS, PhD and MD degrees from the University of Chicago. Her interest in cytogenetics was sparked by her work as a Research Fellow in a clinic for retarded children at Cook County Hospital, Chicago, in the early days of human cytogenetics, and led to postdoctoral research at Oxford University in 1961-62 and again in 1970-71. She developed her academic career at the University of Chicago where she became a full Professor in 1978 even though she worked only three days a week while her children were young. She received certification by the American Board of Medical Genetics in 1982 and was awarded the Blum-Riese Distinquished Service Professorship in 1984.

Dr. Rowley has virtually single-handedly changed the view of the hematology/oncology community and of the cancer biology community regarding the critical importance of recurring chromosome abnormalities in leukemia and lymphoma. She has provided some of the most persuasive evidence that tumours are associated with specific cytogenetic changes which reflect critical genetic changes.

Dr. Langer is the Kenneth J. Germeshausen Professor of Chemical and Biomedical Engineering at the Massachusetts Institute of Technology. The strength of his curriculum vitae is best illustrated by the fact that he has been elected to membership in all three academies - Institute of Medicine of the National Academy of Sciences, National Academy of Engineering and National Academy of Science.

There is general agreement that Dr. Langer pioneered the field of controlled drug release delivery systems (slow release oral systems, transdermal patches, injectable microspheres, and slow release implants). These delivery systems involve macromolecules that have been incorporated into solid polymers from which they are released at controlled rates. This development has revolutionized medical therapy, permitted new therapies for patients, and by reducing the dose administered, has avoided complications and reduced costs. Examples of current drug applications include nitroglycerin, nicotine, cancer chemotheraputics, hormones and vaccines. In subsequent work, he determined the mechanism of release of drugs from polymers and then identified the factors that could be used to control the rate of release.

Dr. Marshall was born in Kagoorlie, Western Australia, and educated in Perth. He graduated in Medicine from the University of Western Australia in 1974. After completion of his postgraduate training, he became a fellow of the Royal Australian College of Physicians (FRACP) in 1983, and held positions in General Medicxine, Microbiology, and Gastroenterology at the Royal Perth Hospital until 1986. In 1986 he joined the Division of Gastroenterology, Faculty of Medicine, University of Virginia, in Charlottesville, VA, where he is currently Clincal Associate Professor. He is also the founder and President of the Helicobacter Foundation in Charlottesville.

When he was a medical resident in 1981, Dr. Marshall and pathologist Dr. Robin Warren noticed that spiral bacteria, though not recognized as common occupants of the human gastric mucosia, were present in over half the patients attending for upper GI endoscopy. In 1982 Dr. Marshall was the chief investigator in a study that established the significance of the new bacterium in gastric ulcer and doudenal ulcer. The organism was isolated and given the name Helicobacter Pylori. Later, initially through experiments with himself as a subject, Dr. Marshall established that gastritis associated with hypochlorhydria is symptomatic of acute H. Pylori infection. Dr. Marshall was the first to appreciate the need for drugs with an antibacterial effect rather than acid-reducing drugs, to reduce the relapse rate in duodenal ulcers.

Dr. James E. Rothman is the Chairman of the Cellular Biochemistry and Biophysics Program of the Rockefeller Research Laboratory at the Memorial Sloan-Kettering Cancer Center in New York. He obtained his BA at Yale University, his PhD at Harvard University under Eugene Kennedy, did a post-doctoral stage in the laboratory of Dr. H. Lodish at MIT, and immediately landed a position in the Department of Biochemistry at Stanford University. After advancing to the rank of Professor in that institution, he became a Squibb Professor of Molecular Biology at Princeton University, and in 1991 became Chairman of the Program in Cellular Biochemistry of the Sloan-Kettering Institute. He is currently also the Vice-Chairman of that Institution.

Dr. Rothman was the first one to develop in vitro assays to reproduce the intricate intracellular movement, targeting and delivery of goods among organelles. These in vitro reconstitution assays continue to be the gold standard in the description of novel intracellular pathways. In addition, together with Dr. Gunter Blobel, Dr. Rothman has made major advances in the discovery of the recognition of the signal peptide of proteins during translation.

Together with Dr. Randy Schekman from Berkeley University, James Rothman developed and exploited the isolation and analysis of mutants of yeast which are defective in intracellular protein transport, and expanded these discoveries to the identification and cloning of the proteins that constitute the ubiquitous machinery of membrane docking and fusion.

Dr. Schekman is Professor and Chair of the Department of Molecular and Cell Biology and Investigator, Howard Hughes Medical Institute, University of California, Berkley. Schekman received his BA in Molecular Biology at UCLA, his PhD in Biochemistry, studying with Arthur Kornberg at Stanford University and he conducted postdoctoral work with S.J. Singer at UCSD. Schekman joined the Berkley facility in 1976.

At Berkley, Schekman initiated studies on the mechanism of protein secretion using the model eukaryotic cell, S. cerevisiae. A classic genetic approach was developed to illuminate the processes of polpeptide import into the endoplasmic reticulum, protein sorting, and packaging into transport vesicles to acceptor membrane compartments. SEC genes that encode the proteins implicated in these processes were cloned and shown to be evolutionary conserved. Mammalian orthologs of the yeast SEC genes are now known to define most aspects of normal and specialized secretory processes. Schekman's group developed complementary biochemical approaches to define the exact roles of SEC proteins. Novel insights included the discovery of the major subunit of the polypeptide translocation channel of the ER (sec61p), the demonstration that cytosolic hsp70 promotes the post-translational translocation of secretory and mitochondrial precursor polypeptide, and the isolation of a novel coat protein complex, COPII, responsible for secretory and membrane cargo sorting and anterograde vesicle budding from the ER.

† 1922-2016

† 1923-2008

Dr. Attardi was born in Sicily and studied medicine at the University of Padua where he obtained his MD degree in 1947. He received his graduate training from the Karolinska Institute in Stockholm, and Washington University in St. Louis. In 1963, Dr Attardi became Associate Professor, Division of Biology at the California Institute of Technology in Pasadena where he is currently Grace C. Steele Professor of Molecular Biology in the Division of Biology. His many honours include the Antonio Feltrinelli International Prize for Medicine and he is a member of the National Academy of Sciences and a Guggenheim Fellow.

Born in Hobart, Tasmania, Australia, she received her BSc and MSc degrees in Biochemistry at the University of Melbourne and her PhD in Molecular Biology in 1975 at the Univ. of Cambridge in the UK. Dr. Blackburn is a member of the National Academy of Sciences and is a recipient of its Award in Molecular Biology. She received the Australia Prize in 1998 and is a fellow of the Royal Society.

Dr. Greider obtained her BA degree in Biology from the University of California at Santa Barbara in 1983. In 1987, she received her PhD from the University of California at Berkeley while working in Dr. Blackburn's laboratory. Dr. Greider received the Schering-Plough Scientific Achievement Award, American Society for Biochemistry and Molecular Biology in 1997 and the Cornelius Rhodes Award in 1996.

† 1939-2019

Dr. Walter Neupert obtained his PhD in Biochemistry in 1968 and his MD in 1970, from the University of Munich. In 1977 he moved to the University of Göttingen until 1983 when he returned to the University of Munich as a Professor of Biochemistry and Cell Biology. Professor Neupert has been a member of the editorial board of numerous journals including Cell, Europeon Molecular Biology Organization Journal, and the Journal of Biological Chemistry. Professor Neupert received the Academia Europaea, the Heinrich-Wieland Prize in 1993 and the Feldberg Foundation Prize in 1996. He is Chairman of the EMBO Council.

† 1936-2015

Dr. Schatz holds a PhD in Chemistry and Biochemistry from the University of Gratz, Austria. He received his postdoctoral training at the University of Vienna. From 1964 to 1966, he worked as a postdoctoral fellow at the Public Health Research Institute of the City of New York on the mechanism of oxidative phosphorylation. After a brief interlude back in Vienna, Dr. Schatz returned to the US in 1968 as Associate Professor at Cornell University. Since 1974, he has been a Professor at the renowned Biozentrum of the University of Basel, Switzerland, of which he was chairman for two years. He has received more than 12 international prizes and medals including the Louis Jeantet Prize for Medicine(1990), the Lynen Medal(1997) and the Otto Warburg Medal(1988).

† 1931-2011

† 1930-2003

Dr. Hershko obtained his MD degree from the Hebrew University-Hadsassah Medical School in 1965 and his PhD in 1969 from Hebrew University. He carried out post-doctorial research at the University of California Medical Centre, San Francisco from 1969 to 1971. Dr. Hershko has pursued his research on intracellular proteolysis at the Technion, where he was appointed Associate Professor in 1972, Professor in 1980 and Distinquished Professor in 1998. Through rigorous biochemical experimentation, Dr. Hershko discovered the role of ubiquitin modification in energy dependent proteolysis and defined the enzymatic machinery that catalyzes ubiquitin conjugation. Since 1987, he has been a member of the Rappaport Institute for Research in the Medical Sciences, and Member, European Molecular Biology Organization (EMBO) since 1993. Dr. Hershko was awarded the Weizmann Prize in 1987 and the Israel Prize in 1994.

Dr. Varshavsky obtained his BSc in Chemistry from Moscow State University in 1970 and his PhD in Biochemistry from the Institute of Molecular Biology in Moscow in 1974. From 1974 to 1977, Dr. Varshavsky directed a research group at the Institute of Molecular Biology. In 1977, he emigrated to the United States to join the Department of Biology at the Massachusetts Institute of Technology as an Assistant Professor. Dr. Varshavsky was appointed Associate Professor in 1980 and Professor in 1986. By genetic analysis in yeast and mammalian tissue culture cells, Dr. Varshavsky elucidated many of the essential roles of the ubiquitin pathway in cellular function. He was elected to the U.S. National Academy of Sciences in 1995 and the American Academy of Arts and Sciences in 1987. He was awarded a National Institutes of Health Merit Award and the Novartis-Drew Award in Biomedical Science in 1998. Dr. Varshavsky moved his laboratory to the California Institute of Technology in 1992.

Dr. Horvitz obtained SB degrees in Mathematics and Economics from MIT in 1968 and his PhD from Harvard University in 1974. During his post-doctoral fellowship with Dr. Sydney Brenner, (Gairdner Awardee 1978, 1991), Dr. Horvitz began using the nematode Caenorhabditis elegans as a simple model system to study development. In 1986, Dr. Horvitz described the genetic basis of programmed cell death in the development of this organism. He discovered many of the regulatory genes controlling apoptosis and showed that similiar genes exist in humans. Horvitz's work definitively showed that apoptosis was a genetically regulated mechanism and has subsequently led to the discovery of countless novel death signalling pathways whose dysregulation directly contributes to human disease. He has consistently published in high-quality journals and has served on many editorial boards, visiting committees and advisory committees. He has received numerous awards for his accomplishments, including the General Motors Cancer Research Foundation, Alfred P. Sloan Jr. Prize in 1998. He is a member of the U.S. National Academy of Sciences as well as a Fellow of the American Academy of Arts and Sciences and the American Academy of Microbiology.

† 1944-2022

Prof. Andrew Wyllie is Head of the Department of Pathology, Cambridge University, United Kingdom and an Honorary Consultant, Addenbrooke's Hospital in Cambridge. Prof. Wyllie trained at the University of Aberdeen where he received his BSc, MB, ChB and PhD In the 1970s and 1980s, Dr. Wyllie coined the term "apoptosis", outlined the cardinal characteristics of this program of cell death and articulated the significance of apoptosis in human disease. The conceptual breakthrough provided by Dr. Wyllie and his subsequent championing of this field have led to numerous presentations at prestigious international symposia. He has been an Editorial Board Member of the Journal of Pathology, Member of the Advisory Editorial Board for the International Review of Experimental Pathology, Editor (Pathology Section) British Journal of Cancer and has been a Member of the Editorial Academy of the International Journal of Oncology since 1992. Among Prof. Wyllie's honours are the Bertner Award, MD Anderson Cancer Centre, University of Texas (1994), Fellow of the Royal Society (1995), Hans Bloemendal Award, University of Nijmegen (1998) and Founder Member, British Academy of Medical Science.

Robert Roeder is honored for his pioneering contributions to the field of transcription of genetic information, a theme of central importance in the biology of eukaryotic (nucleated) cells. He is recognized especially for his description of the complex array of protein factors involved in transcription, notably his analysis of three RNA polymerases and the development of assays for their activities. He has continued to make significant contributions to the identification and cloning of eukaryotic transcription factors and to pursue the detailed characterization of the transcription apparatus and its regulation, work which has important applications in medical science.

Dr. Roeder was born in Indiana where he received his BA and MS, and earned a PhD in biochemistry at the University of Washington, Seattle, in 1969. His interest in transcription began when he was a graduate student. After postdoctoral studies at the Department of Embryology, Carnegie Institute of Washington, Baltimore, he joined the faculty of Washington University School of Medicine, St. Louis. He is now at The Rockefeller University in New York, where he is Professor and Head of the Laboratory of Biochemical and Molecular Biology. He is a member of many scientific organizations including the National Academy of Sciences, the American Association for the Advancement of Science and the American Academy of Arts and Sciences. Among his many honors are the Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Sciences, the Passano Award, the General Motors Cancer Research Foundation's Alfred P. Sloan Prize, the Louisa Gross Horwitz Prize and the National Academy of Sciences - U.S. Steel Award in Molecular Biology.

Roger Kornberg is honored for his pioneering research in the field of transcription, a theme of central importance in the biology of eukaryotic (nucleated) cells. He is recognized primarily for his significant studies of the components involved in the regulation of gene expression. One of his key contributions has been his discovery and detailed description of the nucleosome a structural unit of packaging of chromosomes which has influenced much later work on the structure of chromatin and its role in gene regulation. Dr. Kornberg continues to work on chromatin structure and gene regulation having made many significant contributions.

Dr. Kornberg is a graduate of Harvard University and obtained his PhD at Stanford University. His postdoctoral training was in Cambridge, England, at the MRC Laboratory of Molecular Biology, where he was also later a member of the scientific staff. He went on to be a Junior Fellow at Harvard University and a member of Harvard University School of Medicine. Since 1978, he has been Professor of Structural Biology at Stanford University School of Medicine and was chair of the Department from 1984-1992. His many societal memberships include the National Academy of Sciences and the American Academy of Arts and Sciences. Among his many honors and awards are the Eli Lilly Award, the Passano Award, the Ciba-Drew Award and the Harvey Prize.

Alain Townsend is honored for seminal contributions to the understanding of T-cell activation and its regulation. He observed that T cells can recognize portions of a pathogen that are not expressed on its surface. This gave rise to experiments demonstrating that viral pathogens are degraded inside antigen presenting cells, and ultimately pieces of the virus derived from its core associate with Class I products of the Major Histocompatibility Complex (MHC). Subsequently Dr. Townsend established the essential role of these components in the assembly and surface expression of MHC Class I molecules themselves, leading to the discovery of peptide transporters in the endoplasmic reticulum. These fundamental contributions established the integral role that pathogens play in regulating immune system function, and a new paradigm of MHC gene expression and function relevant to the rational understanding of infectious and autoimmune diseases.

Dr. Townsend is a medical graduate of St. Mary's Hospital, London (1977) where he first developed his interest in human diseases associated with alleles of the MHC complex. He then began graduate study in immunology at the National Institute for Medical Research, Mill Hill, London. In 1984 he joined the Institute of Molecular Medicine, Oxford, and in 1992 became Ad Hominem Professor of Molecular Immunology. Recently he has undertaken further clinical training at the John Radcliffe Hospital where he is an Honorary Consultant in General Internal Medicine. Among other honors he is a Fellow of the Royal Society and an International Research Scholar of the Howard Hughes Medical Institute. His honors include the William B. Coley Award, the Cheadle Medal and Prize for Clinical Medicine and the Louis Jeantet Prize for Medicine.

1934-2022

Emil Unanue is honored for his seminal contributions to the understanding of T-cell activation and its regulation. He showed that T-cells do not recognize intact pathogens but rather, recognize small components of the pathogen presented in the context of Class II products of the Major Histocompatibility Complex (MHC). These components are generated and presented in association with MHC Class II molecules by antigen-presenting cells. The discovery of the molecular and cellular basis of this process has provided a new interpretation of how the cells of the immune system recognize pathogens, and has opened up novel approaches to a rational analysis of the pathobiology of infectious and autoimmune diseases.

Dr. Unanue graduated in medicine in 1960 from the University of Havana, Cuba. He trained from 1961 to 1970 in Pittsburgh and La Jolla in the United States and at the National Institute for Medical Research, Mill Hill, London. In 1985 he joined Harvard University Medical School, where he became Mallinckrodt Professor of Immunopathology. In 1985 he moved to Washington University, St Louis, where he is Mallinckrodt Professor and Chairman of the Department of Pathology and Pathologist-in-Chief of the Barnes Jewish Hospital. Dr. Unanue's long record of distinctions includes the Albert Lasker Basic Medical Research Award and Membership in the Institute of Medicine of the National Academy of Sciences. He has also made distinguished contributions as a speaker, author, editor and member of scientific organizations and has been Chair of the National Academy of Sciences Section of Microbiology and Immunology.

Jack Hirsh is a medical scientist equally at home in the laboratory and the clinical setting. His many distinguished contributions to the field of thromboembolism, which combine basic research, patient management and clinical trials, underlie the therapy of thromboembolism worldwide. His original observation in 1972 of the relationship between the in vitro anticoagulant activity of heparin and its efficacy in patients with venous thrombosis found immediate and widespread clinical application. His subsequent demonstration, with his colleagues, of the superior clinical efficacy of low-molecular-weight heparin revolutionized anti-thrombotic treatment, allowing management on an outpatient basis. His work on oral anticoagulants led to the development of the International Normalized Ratio, an advance in laboratory diagnosis and to clinical trials that assessed the efficacy and risk: benefit ratio of anticoagulants in a variety of clinical situations. Dr. Hirsh and his colleagues also established the value of aspirin in the prevention of stroke. These different but related observations have changed the clinical management of thromboembolism and have had a significant effect on patients' lives.

Born in Australia, Dr. Hirsh is a graduate of the University of Melbourne Medical School. He expanded his background in hematology at Washington University, St. Louis, the London Postgraduate Medical School and the University of Toronto. In 1973 he joined the Faculty of Medicine of McMaster University, Hamilton, where he is now Professor Emeritus of Medicine and is Director, Hamilton Civic Hospital Research Centre. He has received numerous honors including the Trillium Award of Ontario, the Order of Canada and election to the Canadian Medical Hall of Fame.

Much of our present knowledge concerning ion channel structure and function can be traced to Dr. Clay Armstrong. He provided the first general description of the K+ channel pore, including the fundamental ideas of a selectivity filter, a wider inner vestibule and a gate on the inside. A consistent feature of Armstrong's contributions is the absolutely quantitative nature of the work and the resulting fidelity of his clear and concise descriptions. His work has been so profound that it has had enormous influence on the work of others, leading to our present understanding of channel structure and function. Armstrong's seminal work is of enormous value to human disease, the relief of human suffering and the broader aspects of medicine because of subsequent development of drug therapies that work through channels.

Clay Armstrong received his BA degree from Rice University in 1956 and his MD degree from Washington University, St. Louis in 1960. He was a postdoctoral fellow with Dr. K.S. Cole at the NIH from 1961-1964 and with Dr. A.F. Huxley, University College, London from 1964-1966. He has held professorial appointments at Duke University, the University of Rochester and the University of Pennsylvania School of Medicine, where he has been Professor of Physiology since 1976. Among his many honours are election to the National Academy of Sciences, 1987; Columbia University Louisa Gross Horwitz Prize for Biology or Biochemistry (shared with Bertil Hille) 1996; The Albert Lasker Basic Medical Research Award (shared with Bertil Hille and Rod MacKinnon) 1999.

Dr. Bertil Hille has provided medical science with a foundation for modern understanding of ion channels; his findings being as important for cardiac muscle as for the brain. His work has had enormous influence on the work of others, in no small part because his book on ion channels is widely read, being readily understood by novices in the field. Clinical medicine owes the concept of use-dependant block of ion channels by local anesthetics to Hille. He discovered the way that muscarinic acetycholine receptors in the heart, acting through G-proteins, turn on M-type Ca2+channels. He dissected the mechanism for modulation of K+ and N-type Ca2+ channels in sympathetic neurons. These contributions are all relevant to the development of drug therapies that work through channels. Thus Hille's seminal work is of enormous value to human disease and relief of human suffering and to the broader aspects of medicine.

Bertil Hille received his BS degree from Yale University in 1962 and his PhD from Rockefeller University in 1967. He was a postdoctoral fellow with Dr. A.L. Hodgkin at the Physiological Laboratories, Cambridge University from 1967-1968. He has been Assistant, Associate and Full Professor in the Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, since 1968. Among his many honours are: election to the National Academy of Sciences, 1986; Harvey Lecturer, New York, 1986; the Bristol Myers Squibb Award for distinquished Achievement in Neuroscience Research, 1990; Columbia University Louisa Gross Horwitz Prize for Biology or Biochemistry (shared with Clay Armstrong) 1996; The Albert Lasker Basic Medical Research Award (shared with Clay Armstrong and Rod MacKinnon) 1999.

Dr. Roderick MacKinnon's crystal structure of a K+ channel is the end point of a half-century of analysis of cation channel structure-function relationships. It is a stunning accomplishment that solidifies all of the work on the structure of the pore. MacKinnon has driven his field forward with an exceptional focus and intensity. His early work on the pore focussed attention on this critical region; his later work on the crystal structure has opened the field to other investigators who now have a firm basis for further molecular analysis. His work explains at the molecular level, exactly how drugs and toxins alter the properties of channels. His contributions, which are relevant to the development of drug therapies that work through channels. are of enormous value to human disease and relief of human suffering and to the broader aspects of medicine.

Roderick MacKinnon received his BA degree from Brandeis University in 1978 and his MD from Tufts University in 1982. He was a postdoctoral fellow with Dr. R. Morgan at Beth Israel Hospital, Harvard University from 1985-1986 and with Dr. C. Miller at Brandeis University from 1986-1989. He was Assistant, Associate and Full Professor in the Department of Neurobiology, Harvard Medical School from 1989-1996 and since 1996; he has been Professor of Molecular Neurobiology and Biophysics at Rockefeller University. Among his many honours are: election to the National Academy of Sciences, 2000; The Albert Lasker Basic Medical Research Award (shared with Clay Armstrong and Bertil Hille) 1999; and the Lewis S. Rosenstiel Award for Distinguished work in Basic Medical Research, 2000. Dr. MacKinnon is an Investigator for the Howard Hughes Medical Institute.

Dr. Marc Kirschner is the quintessential Cell Biologist. The breadth of his knowledge and the scope of his research are unique: he has made extremely important contributions in three seperate areas of modern Cell Biology. His studies of tubulin and associated proteins constitute a large fraction of our current understanding of the structure, dynamics and regulation of microtubules. In addition, Dr. Kirschner has contributed greatly to the elucidation of the pathways that underlie morphogenesis, using amphibians as a model. Last but not least, he has been instrumental in identifying the elements that control the progression of the cell cycle. Dr. Kirschner's versatility and integrative ability are unprecedented in modern Biology.

Dr. Kirschner is a graduate of Northwestern University and obtained his PhD degree from the University of California at Berkeley. His postdoctoral training was initially at Berkeley and subsequently at Oxford, UK. In 1972, he was appointed Assistant Professor at Princeton University where he remained until 1978, the year he was promoted to Professor of Biochemical Sciences. He next spent fifteen years at the University of California, San Francisco, before becoming Chair of the Department of Cell Biology at Harvard in 1993. Dr. Kirschner is a member of the National Academy of Sciences of the USA and is a Foreign Member of the Royal Society of London and of the Academia Europaea.

Henry Friesen also received the Canada Gairdner Wightman Award in 2001 for his leadership to Canadian medical research and especially for leading to the establishment of the Canadian Institutes of Health Research.

Dr. James Watson has enjoyed international recognition since 1953, as the co-discoverer with Francis Crick of the double helical structure of DNA. For this feat he, Crick and Maurice Wilkins, were jointly awarded the 1962 Nobel Prize in Medicine. Today he is recognized as the major figure behind the Human Genome Project. He was the Director of the National Center for Genome Research from 1989 to 1992. In that role he recruited key scientists to the project, as well as professionals concerned with ethical, legal and social issues. His contributions of creativity, vision and intuition have been of immeasurable value to the Human Genome Project.

Dr. Watson graduated in zoology from the University of Chicago and earned a PhD at Indiana University. He was a postgraduate student at the University of Cambridge when the breakthrough in DNA research occurred. He has been a faculty member at Harvard since 1968 and has been a Director and later President at the Cold Spring Harbor Laboratory, with a three-year hiatus at the National Center for Genome Research in Washington, during which the Human Genome Project was born. Among innumerable honors, he has recently been named an honorary Knight of the British Empire by Queen Elizabeth.

Dr. Green, a mathematician, has had a broad and profound impact on the development and success of genome analysis. His software has made possible the automated sequencing of the three billion base pairs in the human genome and represents the most important technical advance in DNA sequencing of the 1990's. He was the first to recognize that only a subset of genes evolve sufficiently slowly to maintain recognizable sequence similarity across phylogenetically distant groups and was one of the first to recognize that the true number of human genes was much less than the 100,000 previously estimated.

Dr. Green is a graduate of Harvard University and the University of California at Berkeley and has also worked at the Institute for Advanced Study, Princeton, Columbia University, the University of North Carolina at Chapel Hill, Collaborative Research Inc. and Washington University, St. Louis. Since 1994 he has been at the University of Washington, Seattle. He is an Investigator of the Howard Hughes Medical Institute and has been elected to the National Academy of Sciences.

Dr. Eric Lander has been one of the driving forces behind the genomics revolution. The Whitehead Institute Center for Genome Research, of which he is the founder and Director, has been responsible for developing key tools of modern mammalian genomics. The Center has identified numerous human genes and has made the data available to the scientific community. Dr. Lander and his colleagues have also pioneered in the application of genomics to biomedical research, such as methods for analyzing complex genetic traits. Among diseases of special interest to his group are cancer, diabetes, hypertension and dwarfism.

Dr. Lander is a geneticist, mathematician and molecular biologist. He graduated in mathematics at Princeton, was named a Rhodes Scholar and earned a PhD at the University of Oxford. Concurrently with his Whitehead Institute role, he is a Professor of Biology at the Massachusetts Institute of Technology. He is an enthusiastic teacher who has won the Baker Memorial Award for Undergraduate Teaching at MIT. Among many other distinctions, he was selected to deliver a special Millennium Lecture at the White House in 2000.

Dr. Robert Waterston is a graduate of Princeton University and received his MD and PhD degrees from the University of Chicago. One of the first graduate students of Sydney Brenner in Cambridge, he set up an independent laboratory that helped to establish the nematode worm c. elegans as a powerful experimental organism. Following a second visit to Cambridge to work with John Sulston in 1985, his work increasingly concentrated on genomic mapping and sequencing. Building on his experience, he led one of the teams that published the working draft of the human genome in 2001.

Dr. Waterston was at Washington University, St. Louis, MI, from 1976-2003 and moved to University of Washington, Seattle in 2003. He has had close scientific collaborations with many prominent genome researchers on both sides of the Atlantic and had a pivotal role in the completion of the first rough draft of the human genome in 1990.

Dr. Maynard Olson was one of the first to recognize the potential of genome analysis and to develop experimental techniques for analysis of complex genomes. He developed the technologies of yeast-artificial-chromosome (YAC) cloning and sequence-tagged-site (STS) mapping that provided a direct path to the Human Genome Project. The YAC system has become routine for positional cloning of genes involved in human diseases and was the prototype for other large-fragment cloning systems that play a central role in genome analysis.

Dr. Olson graduated from the California Institute of Technology and earned a Ph.D. in chemistry at Stanford. His major interest changed to genetics during his faculty positions at Dartmouth College, the University of Washington, Seattle and Washington University, St. Louis, where he became a Professor of Genetics. In 1992 he returned to Seattle and is now Professor of Medicine (Division of Medical Genetics) and Professor of Genetics, as well as Adjunct Professor of Computer Science. He is also Chairman of the Genome Research Review Committee of the NIH Genome Research Institute. His many honors include the 1992 Genetics Society of America Medal.

Dr. Craig Venter has played a vital role in the sequencing and analysis of the human genome. His accomplishments in the development of methods for decoding genetic sequences, notably expressed-sequence tags (ESTs) and in bioinformatics, have provided a foundation for understanding the relationships between species and the biology of microbes. He is known for the so-called "shotgun sequencing" strategy, which accelerates sequencing and is now a central component of all whole genome-sequencing strategies.

Dr. Venter served with Navy Medical Corps in Vietnam in 1967-68 and received a PhD from the University of California, San Diego, in 1975. He joined the State University of New York (SUNY) at Buffalo and later went to NIH in the National Institutes of Neurological Disorders and Stroke. In 1992 he left NIH to found The Institute of Genomic Research (TIGR). In 1998, with the Perkins-Elmer Corporation, he founded Celera Genomics. His many honors include the 2001 Taylor International Prize in Medicine from the Robarts Research Institute, London, Ontario.

Dr. Michael Waterman is responsible for the introduction of some of the most important mathematical concepts, statistical models and computer algorithms used for genome analysis. He pioneered RNA secondary structure prediction, evolutionary tree comparison, gapped alignment, parametric alignment and other sequence analyses. He has recently released a new algorithm representing a remarkable improvement in the efficiency and accuracy of genome sequence assembly. He has trained many prominent computational genomicists and has been a prime mover in the development of the field.

Dr. Waterman graduated in mathematics from Oregon State University and obtained his Ph.D. from Michigan State. He has been a faculty member at Idaho State University and at the Los Alamos Scientific Laboratory and since 1982 has been at the University of Southern California, where he is a Professor of Biological Sciences, Mathematics and Computer Science as well as a University Professor.

Dr. Jean Weissenbach is recognized for his work in human molecular genetics, particularly his studies of the human sex chromosomes, linkage mapping and the mapping and cloning of disease genes. His studies of linkage led to the construction of the first extensive map of the human genome and greatly accelerated this field, while his own research on disease genes and his extensive network of collaborations demonstrated the usefulness of unpublished data from the genetic linkage map.

Dr. Weissenbach received his PhD from the University of Strasbourg in Molecular Biology and has worked at the University of Strasbourg, the Pasteur Institute and Genethon. He is currently Director of Genoscope, the French National Sequencing Centre, which is actively contributing to the sequencing of genes on chromosome 14.

Dr. Collins is a graduate of the University of Virginia with a PhD in Physical Chemistry from Yale and an MD from the University of North Carolina. After a fellowship in Human Genetics and Pediatrics at Yale, he joined the University of Michigan, Ann Arbor, where he remained until he was appointed to replace James Watson at NIH in 1993. His research has contributed to the identification of the genes for cystic fibrosis, neurofibromatosis and Huntington disease.

Francis Collins also received the Canada Gairdner International Award in 2002 for his outstanding leadership in the Human Genome Project and particularly for the international effort to map and sequence the human and other genomes. As of 2002, Dr. Francis Collins was the current Director of the National Human Genome Research Institute of the National Institutes of Health, USA. In this role he oversees the Human Genome Project, the complex multidisciplinary scientific exercise directed at mapping and sequencing the entire human DNA and determining aspects of its function. An initial analysis of the human genome sequence was published in 2001 and the data has been made available to the scientific community.

† 1942-2018

Sir John Sulston's recognition of the value of the nematode worm c. elegans as an experimental organism and his achievement in mapping the developmental lineage of all its 959 somatic cells led to his first Gairdner Award with Sydney Brenner in 1991. He went on to sequence the c. elegans genome in collaboration with Robert Waterston; completed in 1998, this was the first animal genome to be sequenced. He has played a major role in the Human Genome Project, both personally and through the Sanger Centre, which he founded in 1993 for the mapping and sequencing of the human and other genomes and served as Director from 1992-2000.

Dr. Sulston has spent virtually his entire career at the University of Cambridge. He earned a BA in organic chemistry and a PhD, spent three years as a postdoctoral fellow at the Salk Institute and then returned to Cambridge as a member of the Laboratory of Molecular Biology. He has received numerous honors and in 2001 was knighted in the New Year's Honour list.

† 1943-2011

Ralph Steinman was a cell biologist whose research focused on the immune system including the human immune system in the setting of several diseases. He and his collaborators discovered a previously unknown class of immune cells, called dendritic cells. Dendritic cells are important and unique accessories in the onset of several immune responses including graft rejection, resistance to tumors, autoimmune diseases, and infections such as AIDS.

Ralph Steinman, born in Montreal, Canada, he received a BS degree, with honors, from McGill University in 1963, and an MD, magna cum laude, from Harvard Medical School in 1968. After completing an internship and residency at Massachusetts General Hospital, he joined The Rockefeller University in 1970 as a postdoctoral fellow in the Laboratory Cellular Physiology and Immunology headed by Dr. Zanvil A.Cohn and the late James G. Hirsch. He was named Henry G. Kunkel Professor in 1995, and Director of the Chris Browne Center for Immunology and Immune Diseases in 1998.

Ralph Steinman is editor of the Journal of Experimental Medicine and serves on numerous editorial and advisory boards. He is a member of the National Academy of Sciences USA and has received many international awards including the Freidrich-Sasse, Emil von Behring, and Robert Koch Prizes, the Rudolf Virchow and Coley Medals.

Richard Axel's laboratory studies how sensory information is represented in the brain. Olfactory sensory neurons expressing a given receptor project to spatially invariant loci in the brain to create a topographic map of olfactory information. His studies suggest a mechanism by which this sensory map may be translated in higher brain centers to allow for the discrimination of odors and appropriate behavioral responses.

Richard Axel received his degree from Columbia College and his MD degree from the Johns Hopkins University School of Medicine. He then held fellowships in the Columbia University Institute of Cancer Research and at the National Institutes of Health. Dr. Axel is a member of the National Academy of Sciences and the American Academy of Arts and Sciences. Among his many honors are the Eli Lilly Award in biological chemistry, the Richard Lounsbery Award from the National Academy of Sciences and the Bristol-Myers Squibb Award for distinguished achievement in neuroscience research.

Linda Buck explores the mechanisms underlying smell, taste, and pheromone sensing in mammals. In the olfactory system, hundreds of different odorant receptors are used in a combinatorial fashion to encode the identities of thousands of odorous chemicals. Studies using receptor genes as molecular and genetic tools have revealed how these combinatorial codes are represented in the nose, olfactory bulb, and olfactory cortex to ultimately generate diverse odor perceptions.

Linda Buck received her undergraduate degree from the University of Washington, Seattle, and her PhD degree from the University of Texas Southwestern Medical Center at Dallas. She did postdoctoral research in neuroscience at Columbia University College of Physicians and Surgeon. Linda Buck's honors include the Lewis S. Rosenstiel Award for distinguished work in basic medical research, the Louis Vuitton-Moet Hennessy Science for Art Prize, the R. H. Wright Award in olfactory research, the Unilever Science Award. Linda Buck is a Fellow of the American Association for the Advancement of Science and a member of the National Academy of Sciences.

Wayne Hendrickson's pioneering studies of the anomalous dispersion effect have established this technique as the method of choice for determining protein crystal structures in as rapid and straightforward manner as possible and has made the concept of structural genomics an experimental reality. In addition to his central role in the development of multi-wavelength anomalous diffraction (MAD) methods, he was also a pioneer in the development of computer programs that are used to build and refine atomic models for proteins on the basis of X-ray diffraction measurements. His contributions to methodology are complemented by his determination of the first structure of a tyrosine kinase and the structure of the HIV protein, gp120, in complex with the CD4 receptor and a neutralizing human antibody.

Wayne Hendrickson was born in Spring Valley, Wisconsin, he received his BA in Physics and Biology at the University of Wisconsin and his PhD in Biophysics from Johns Hopkins University, followed by postdoctoral work at the Naval Research Laboratory in Washington. In 1984, he joined the faculty of the Department of Biochemistry and Molecular Biophysics at Columbia. Wayne Hendrickson is a member of the National Academy of Sciences and is a recipient of several awards including the Alexander Hollaender Award of the National Academy of Sciences, the Christian B. Anfinsen Award of the Protein Society, the Merit Award of the National Institutes of Health, the Academy Medal, New York Academy of Medicine (2003), the Paul Janssen Prize (with M. G. Rossmann), Rutgers University (2004), and the Harvery Prize, Technion - Israel Institute of Technology (2004).

Seiji Ogawa discovered that Magnetic Resonance Imaging (MRI) could be used to visualize active regions in the living human brain. He showed that this functional brain mapping depended on the oxygenation status of the blood feeding the active neurons. Functional MRI (fMRI) has been used to map the visual, auditory and sensory regions. It is used in surgical planning to identify the motor cortex. fMRI is a revolutionary tool for neuroscience and has become essential for investigating higher order cognitive function and brain interconnectivity and plasticity.

Seiji Ogawa trained as an applied physicist in Tokyo and as a PhD chemist at Stanford. He joined the Technical Staff in Biophysics Research at the Bell Laboratories in Murray Hill, NJ where he became a Distinguished Member and where he stayed for 33 years. Since 2001, he has been Director of the Ogawa Laboratories for Brain Function Research in Tokyo. He is the recipient of a number of awards in Magnetic Resonance, is a member of the Institute of Medicine of the National Academy of Sciences and this year was awarded the Japan International Prize.

John Ellis was a leader in the field of chloroplast biogenesis. He studied the biochemistry of the development of chloroplasts in higher plants. In 1980 Ellis discovered the first molecular chaperone. He found that in chloroplasts unassembled subunits of the rubisco complex were associated with another protein which turned out to be a chaperone. These seminal experiments foreshadowed the discoveries of Horwich and Hartl. Ellis subsequently made substantial contributions to the concept of molecular chaperones which are required to assist a variety of cellular processes in all types of cells.

Dr. Ellis earned his doctorate in 1960 from King's College, London for research on transamination reactions with Professor Davies. Postdoctoral studies were done at Oxford in the Biochemistry Department on sulfate reduction in bacteria with Professor Pasternak. In 1964 Dr. Ellis joined the Departments of Botany and Biochemistry at the University of Aberdeen. He moved to the newly founded Department of Biological Sciences at the University of Warwick in 1970 as Senior Lecturer and Head of the Chloroplast Research Group. In 1976 was awarded a Personal Chair in the department and in 1983 was elected to the Royal Society.

F. Ulrich Hartl's research is in mechanisms of cellular protein folding, specifically the structure and function of molecular chaperones. He delineated, resolved and reconstituted the complete pathway by which molecular chaperones cooperate to fold proteins in the living cell. In a series of elegant studies he established how the folding protein is recognized by one chaperone, thereby preventing premature misfolding, and then transferred to a molecular machine which promotes proper folding. While initially highly controversial, this mechanism is now well accepted and confirmed by x-ray crystallography. When these protein folding pathways are saturated or non-functional, protein aggregates accumulate in the cell. Examples of diseases that are likely the result of such aggregates are Alzheimer's and Huntington's Diseases.

Dr. Hartl earned his medical degree from the University of Heidelberg in 1990. He began his postdoctoral fellowship in organelle biogenesis at the Institute of Physiological Chemistry at the University of Munich and continued his studies in protein secretion at the University of California at Los Angeles. From 1993 to 1997, Dr. Hartl was an Associate Professor of Cell Biology and Genetics at Cornell University School of Medical Sciences. He received the Howard Hughes Award in 1994 and was an Associate Investigator for the Howard Hughes Medical Institute. In 1995 he was appointed to the William E. Snee Chair of Cellular Biochemistry at Memorial Sloan-Kettering Cancer Center. Dr. Hartl was appointed managing Director of the Max-Planck-Institut fur Biochemie, Germany in 1997.

Arthur Horwich is a pioneer in the field of molecular chaperones. These are a special class of proteins that assist other proteins in folding into their final form, which determines their function. Horwich discovered an accessory protein that is required for folding of proteins imported into mitochondria. He then led the way in understanding the cavity-based chaperonins GroEL/GroES. His discoveries have advanced the understanding of protein folding and have profound implications for diseases, such as Alzheimer's, that are thought to result from protein misfolding.

Arthur Horwich received AB and MD from Brown University in 1973, trained in clinical pediatrics at Yale, and then pursued postdoctoral fellowship training first at the Salk Institute in the Tumor Virology Laboratory with Walter Eckhart and then at Yale in Medical Genetics with Leon Rosenberg. Dr. Horwich is a recipient of the 2001 Hans Neurath Award. He is a member of the National Academy of Sciences.

†1935-2019

Dr. George Sachs is an exemplary bench to bedside medical scientist. He discovered the proton or acid pump in the stomach and then led the development of H+K+ dependent ATPase inhibitors or PPI's. These agents have truly revolutionized the therapy for gastric acid disorders such as ulcers and gasttroesophageal reflux, which has benefited millions of patients, reduced greatly the need for surgery and simultaneously created a billion dollar industry. Dr. Sachs continues his translational research in defining mechanisms for gastric disease and producing new agents to optimize treatment.

Dr. Sachs, born in Austria, is a medical graduate of the University of Edinburgh in 1960. He was on the faculty of the University of Alabama from 1963 - 1982 as Professor of Medicine and Physiology and Director of Membrane Biology. In 1982 he became the Wilshire Chair in Medicine and Professor, Medicine and Physiology at the University of California, Los Angeles. In 1987 he became Director of Membrane Biology Laboratory and Co-Director - Center for Ulcer Research & Education. Dr. Sachs has had many professional and editorial responsibilities and his honours include the Beaumont Prize and the Hoffman LaRoche Award.

† 1931-2014

The incidence of obesity is reaching epidemic proportions in developed countries. Importantly, Douglas Coleman is a pioneer in the field of obesity. His innovative studies in mouse genetic models of obesity in the early 1970s provided compelling evidence for the existence of a hormone system that participated in the control of fat cell homeostasis. His research was the first to hint that the "dumb" fat cell participates in regulating the integrative biology of metabolism and weight control. Using elegant parabiosis cross-circulation protocols he noted that deficiency of a circulating "satiety" factor, or resistance to a circulating "satiety" factor, explained the phenotype of the obese (ob) and diabetes (db) mice, respectively. He concluded that the circulating factor would be fat cell-derived. The ob and db mice are now known to carry mutations in the leptin ligand and leptin receptor, respectively. These seminal findings, performed using integrative physiologic approaches, provided breakthrough insights into the causes of obesity.

Douglas Coleman was born and raised in Stratford, Ontario, Canada, and received his BSc degree from McMaster University in 1954. He completed his PhD at the University of Wisconsin in Biochemistry in 1958. His full career has been spent at the Jackson Laboratory in Bar Harbour, Maine, where he performed his classic parabiosis studies. Douglas Coleman is a recipient of numerous prestigious awards and accolades including the Claude Bernard Medal (1977) and membership in the National Academy of Sciences (1998).

For more than 50 years, the name of Professor Brenda Milner has been synonymous with memory. In the early 1950s, in collaboration with Dr.Wilder Penfield at the Montreal Neurological Institute/McGill University, she made various seminal contributions on the key role of the hippocampus and temporal lobes in recent memory events. The origins of modern cognitive neuroscience of memory can be traced directly to her rigorous and imaginative studies. She continues to pursue her research activities using modern brain imaging to dissect even further key components and regions functionally involved in cognitive processes. Her research has paved the way to molecularly-oriented approaches aimed at deciphering key genomic and cellular steps leading to memory traces.

Brenda Milner earned her BA (1939) in Experimental Psychology and her ScD (1972) from the University of Cambridge, and her PhD from McGill University in 1952 for research on intellectual effects of temporal-lobe damage in man with Professor D.O. Hebb. Since her service at the Universite de Montreal as Professeur agrege at the Institut de psychologie (1944-1952), she has been associated with McGill University, where she first became Research Associate in the Psychology Department in 1952. She has received a large number of national and international awards including 19 honorary degrees, fellowships in the Royal Society of Canada (1975) and of London (1979), the Foreign Associate title at the National Academy of Sciences - USA (1976), Officers of the Order of Canada (1984) and of Quebec (1985), first recipient of the Wilder Penfield Prize for Biomedical Research (Quebec, 1993), member of the Canadian Medical Hall of Fame (1997), Golden Jubilee Medal of Her Majesty Queen Elizabeth II (2002) and the National Academy of Sciences Award in the Neurosciences, USA (2004) and, the most recent, Companion of the Order of Canada (2005)

Endel Tulving has clarified the nature of human memory at the behavioural level and made substantial additions to our knowledge of its neural correlates. His theorizing is of unusual breadth and coherence, has dealt with the relations between memory and consciousness at the experimental level, with the measurement of memory organization at the behavioural level, with methods for distinguishing memory systems at the experimental level, and with the neuroanatomical correlates of memory systems and processes at the level of brain mechanisms. In an incredibly productive career spanning nearly half a century, he has radically changed how scientists view human memory, and his theoretical frameworks now guide the whole field of memory research.

Dr. Tulving was born in Estonia, moving to Canada as a young adult. He earned his doctorate from Harvard University in 1957 and accepted a position at the University of Toronto. He remained in Toronto (except for a brief period at Yale University), serving as Chair of the Department of Psychology from 1974 to 1980, and becoming University Professor in 1985. He joined The Rotman Research Institute of Baycrest Centre in 1992 as the Tanenbaum Chair and is also the Clark Way Harrison Distinguished Visiting Professor of Psychology and Cognitive Neuroscience, Washington University in St. Louis. He is a member of seven distinguished societies: Fellow, Royal Society of Canada; Foreign Member, Royal Swedish Academy of Sciences; Fellow, Royal Society of London; Foreign Honorary Member, American Academy of Arts and Sciences; Foreign Associate, National Academy of Sciences, U.S.A; Foreign Member Academia Europaea; Foreign Member, Estonian Academy of Sciences. He has also been the recipient of numerous prestigious awards, including the Distinguished Scientific Contribution Award (American Psychological Association), Gold Medal Award for Life Achievement in Psychological Science (American Psychological Foundation), and the Izaak Walton Killam Memorial Prize for Distinguished Career Contributions to the Field of Natural Sciences (Canada Council).

Jeffrey M. Friedman is a leader in the biology of the mechanisms that control body weight. In 1994 he completed an investigative "tour de force" that spanned nearly a decade when he discovered the genetic defect in the murine "obese" (ob) mutant. Leptin was the first fat cell-derived hormone to be discovered. Building on the seminal early work of Douglas Coleman (2005 Gairdner International Award Winner) he employed positional cloning approaches to characterize the defective gene well before the advent of today's repositories of gene sequence and sophisticated investigative genetic tools and informative DNA markers. The isolation of the gene rapidly led to his integrative studies which helped define the biological effects of leptin at the whole animal level and the elucidation of a genetic defect in the leptin receptor in the "diabetes" (db) mouse model of obesity. Taken together his work provided the "spark" that has ignited an international frenzy of academic and industry-based research into the study of the causes and treatment options for obesity. The discovery of leptin and newer studies defining the link between leptin released from fat cells and modulation of brain function by leptin have fundamentally advanced our understanding of the control of total body fat content.

Jeffrey M. Friedman, born in Orlando, Florida, received his medical degree from Albany Medical College of Union University and residency training in Internal Medicine at Albany Medical Center Hospital. He received his PhD degree in 1986 from the Rockefeller University and later joined the Faculty, where he is presently Professor and an Investigator of the Howard Hughes Medical Institute. Most recently, he has been awarded many accolades and awards including membership in the National Academy of Sciences (2001) and the Bristol-Meyers Squibb Award for Distinguished Achievement in Metabolic.

Andrew Fire, with his studies on gene regulation in the nematode Caenorhabditis elegans, has made important contributions to describing and elucidating mechanisms of gene silencing by double stranded RNA. This paradigm of gene silencing contributed to by the work of Fire has been described as "one of the most exciting discoveries of recent times in molecular biology". Much effort has been focused on the efficacy of a system that can use just a few molecules of dsRNA to silence a large population of target molecules. The underlying responses to these silencing triggers are present in many organisms, and in plants have clearly been shown to be involved in response to pathogenic challenges. These gene silencing processes in animal systems have a role in viral pathogenesis and in tumor progression in mammalian systems.

Andrew Fire is a native of Santa Clara County, California. Dr. Fire received training at UC Berkeley receiving a BA in mathematics in 1978. He received his PhD in biology from MIT in 1983 studying with Dr. Philip Sharp and did postdoctoral work at the Medical Research Council laboratory in Cambridge, UK in the group of Dr. Sydney Brenner from1983-1986. From 1986 to 2003, Dr. Fire was on the staff of the Carnegie Institution of Washington's Department of Embryology in Baltimore, Maryland during which time he was also Adjunct Professor of Biology at Johns Hopkins University. In 2003, Dr. Fire joined the faculty as Professor in the Departments of Pathology and Genetics at Stanford University School of Medicine. He is a member of the National Academy of Sciences and a recipient of many awards and prizes including the Wiley Prize, Rockefeller University in 2003, the National Academy of Sciences Molecular Biology Award in 2003, and the H.P. Heineken Prize in Biochemistry and Biophysics from the Netherlands Academy of Sciences in 2004.

Craig Mello is a pioneer in the field of regulation of gene expression by small RNA molecules, an area recently described as "arguably the most important advance in biology in decades". His studies, focused through elegant experiments with a very powerful model organism, the nematode Caenorhabditis elegans, were and continue to be instrumental in elucidating mechanisms of gene regulation through short double-stranded RNAs, short interfering siRNA. This work has opened the field that has been named as RNA-mediated interference (RNAi) by Mello. RNAi has become an extremely powerful tool for basic studies on gene silencing and has led the way to important practical applications in biotechnology and medicine.

Craig Mello received his ScB in Biochemistry from Brown University in 1982 and additional training in Developmental Biology at the University of Colorado from 1982-1984. He went on to do doctoral work at Harvard University receiving his PhD in 1990, and postdoctoral work from 1990-1994 at the Fred Hutchinson Cancer Research Center in Seattle. Dr. Mello is the recipient of many honors and awards including the Wiley Prize, Rockefeller University in 2003, and the National Academy of Sciences Molecular Biology Award in 2003. He has been an Assistant Investigator of the Howard Hughes Medical Institute since 2000 and holder of the Blais University Chair in Molecular Medicine at the University of Massachusetts Medical School since 2003.

Dr. Ronald has had an outstanding career as a leader at the University of Manitoba, as the physician who provided the leadership in launching the subspecialty of infectious diseases in Canada, and as a leader in the fight against HIV/AIDS in East Africa. He is known in both the developed world and in East Africa for his research as a clinical scientist and as a humanitarian who has given selflessly in nurturing others. He mentored 70 infectious diseases Fellows who have gone on to populate Canadian academic institutions. He began a shared program with the University of Nairobi where over 80 Africans have received MSc or PhD degrees, and in collaboration with major universities over 300 peer-reviewed papers have been published. Central to these have been studies on the epidemiology of HIV and other sexually transmitted diseases.

Dr. Ronald was born in Manitoba and graduated in medicine from the University of Manitoba (1961). He trained in Internal Medicine at the University of Maryland (1962-64) and was a Fellow in Infectious Diseases at the University of Washington (1965-68). He joined the Faculty of Medicine in the Department of Microbiology and Internal Medicine at the University of Manitoba in 1968, rising to the rank of Professor (1977) and Distinguished Professor (1986). Dr. Ronald was head of the Department of Medical Microbiology (1976-1985), and H.E. Sellers Professor and Head of Internal Medicine (1983-1990).

Dr. Ronald has held many international appointments including: founding member University of Manitoba/University of Nairobi/WHO Research and Training Program on Sexually Transmitted Diseases and Chair, Diagnostics Committee (1989-2004) and President of the International Society for Infectious Diseases (1996-98). He is an Officer of the Order of Canada, Fellow of the Royal Society of Canada, member of the American Association of Physicians, and recipient of the International St Boniface Hospital Award and the F.N.G. Starr Award (CMA).

Dr. Ralph Brinster is a pioneer in the development of techniques for manipulating the cellular and genetic composition of early mouse embryos. These techniques have made the mouse the major genetic model for understanding the basis of human biology and disease. He began his work by showing how mouse embryos could be cultured in a Petri dish in a simple culture medium and then showing how cells could be added to such embryos to make animals of mixed cell origins or chimeras. This work was a key enabler of targeted mutagenesis in embryonic stem cells, which has revolutionized our ability to understand gene function in mammals. He is acknowledged as the founder of the field of mammalian transgenesis, with its applications to human disease models and biotechnology. In recent years he has developed new models of germline manipulation using sperm progenitor cell transplants. In all these studies, Dr. Brinster has been an innovator, a perfectionist and a forward thinker, understanding clearly the need to develop enabling technologies to pursue novel biological questions. His range of contributions is unmatched in the field.

Dr. Brinster grew up on a small farm in Cedar Grove, New Jersey, where some of his early experiences with animals included, as a teenager, running a small poultry business, which helped finance his studies in veterinary medicine. After completing his DVM and PhD studies at the University of Pennsylvania, he joined the faculty of the School of Veterinary Medicine there in 1960. He remains on faculty today as Richard King Mellon Professor of Reproductive Physiology in the School of Veterinary Medicine. He is a member of the National Academy and the Institute of Medicine and has received many awards and honours including the Wolf Prize, 2003 and the first March of Dimes Prize in Developmental Biology in 1996.

Ronald A. Evans' scientific contributions in the field of nuclear receptors and their function have been seminal. His work is in an area that has wide medical application. In 1985, his cloning and characterization of the first nuclear hormone receptor, the human glucocorticoid receptor, heralded a "molecular revolution" that transformed the field and, with it our understanding of how hormones, fat-soluble vitamins and dietary lipids elicit changes in gene expression in health and disease. In the years that followed, he uncovered nearly 50 such receptors that, taken together, constitute the nuclear receptor superfamily and represent an important mechanistic link between diet, exercise and a myriad of human diseases, including cancers, diabetes and osteoporosis. Particularly noteworthy was the discovery of the peroxisome proliferator-activated receptor (PPAR) family of orphan receptors that provided "a molecular interface between dietary fats and the genome."

Ronald M. Evans, born in East Los Angeles, California, received his BA in Bacteriology (1970) and PhD in Microbiology (1974) at the University of California, Los Angeles (UCLA). He completed postdoctoral work at the Rockefeller University in New York in the laboratory of Dr. James Darnell. In 1978, he joined the faculty of the Salk Institute for Biological Studies in La Jolla, California. He is currently the March of Dimes Chair in Molecular and Developmental Biology at the Salk Institute and an Investigator of the Howard Hughes Medical Institute. He is a recipient of numerous awards including membership in the National Academy of Sciences (1989), the 1st Bristol-Meyers Squibb Award for Distinguished Achievement in Metabolic Research (2000), the Albert Lasker Basic Medical Research Award (2004) and the "Grande Medaille D'Or" from the French Academy of Sciences.

† 1952-2015

Prof. Alan Hall has been a pioneer in showing how external signals control the cellular cytoskeleton, composed of proteins such as actin, which in turn organizes the shape and movement of cells. His research revealed a series of crucial molecular switches (called Rho GTPases), which acting together determine when and where the cell's outer membrane and actin cytoskeleton become rearranged to drive changes in cell migration. These are crucial features of cellular function in normal tissues, and critical for the aberrant behaviour of cancer cells. Dr. Hall's work has therefore transformed our understanding of the biology of human cells.

Prof. Hall was born in England and received his BA in Chemistry at Oxford. He obtained his PhD from Harvard University (1977). Following postdoctoral training in Edinburgh and Zurich, he became a group leader at the Chester Beatty Laboratories in London (1981), where he was promoted to Professor (1989). He was appointed as Professor at the University College London (1993) and became Director of the Medical Research Council Laboratory for Molecular Cell Biology and Cell Biology Unit at the University College London (2001). In April 2006, he became Chair of the Cell Biology program at Memorial Sloan Kettering Cancer Center in New York.

Prof. Hall holds many prominent editorial and advisory positions. He has won a number of prestigious awards including the Feldberg Foundation Prize, the Novartis Medal and the Louis-Jeantet Prize. He is a Fellow of the Royal Society, the Academy of Medical Sciences, and the European Molecular Biology Organization.

Dr. Thomas Pollard pioneered the biochemical and biophysical analysis of the actin cytoskeleton, which is responsible for form and movement in all cells. His many contributions have defined the actin cytoskeleton field for nearly three decades, and include the basis for directional actin polymerization, the discovery of actin capping, severing and nucleation factors and the mechanisms of actin-based intracellular movement. The complex actin-based cytoskeletal network underlies cell shape and motility in virtually all biological contexts, including intracellular transport, polarized cell growth and division, tissue formation and developmental morphogenesis. In addition, actin dynamics is essential for virulence of a number of human bacterial pathogens.

Dr. Thomas Pollard obtained his MD from Harvard Medical School (1968) and became a staff associate at the National Institutes of Health in 1969. He returned to Harvard in 1972, and was promoted to Associate Professor (1975). He was Professor and Director of the Department of Cell Biology and Anatomy at Johns Hopkins Medical School from 1987-1996. He assumed the Presidency of the Salk Institute in 1996, where he was also Professor and an Adjunct Professor at UCSD. He moved to Yale University in 2001, where he is currently the Eugene Higgins Professor and Chair of the Department of Molecular, Cellular and Developmental Biology.

Dr. Pollard has held innumerable prestigious advisory and editorial board positions, including the Presidency of the American Society for Cell Biology and the Biophysical Society. He is a Fellow of the American Academy of Arts and Sciences, the National Academy of Sciences of the United States, the American Society of Microbiology, and the Biophysical Society. He has given many named lectures and won a number of prestigious awards including a Guggenheim Fellowship, the Rosensteil Award and the E.B. Wilson Medal. He is also a renowned mentor, for which he has won numerous teaching awards.

Joan Steitz has been a leader in the field of RNA biology for a generation, from her graduate work on the structure and function of RNA in RNA-containing bacterial viruses (bacteriophages), to the discovery of the role of small nuclear and nucleolar ribonucleoprotein particles (snRNPs and snoRNPs) in RNA processing, and the discovery of a rare mRNA processing pathway. She has worked with many different biological systems, from bacterial viruses to unicellular eukaryotes, to other eukaryotic model organisms, to mammalian systems including human to address key questions about fundamental biological questions. Her enthusiasm for scientific research has been influential in the education, training, and mentoring of numerous students and postdoctoral fellows, particularly women, many who have gone on to exceptional careers and contributions of their own.

Joan Steitz, a native of Minneapolis, Minnesota received her BS in Chemistry (1963) from Antioch College, Ohio and a PhD in Biochemistry and Molecular Biology (1967) from Harvard University, working with Nobel Prize winner Dr. James Watson. Following postdoctoral studies at the Division of Cell Biology, Medical Research Council Laboratory of Molecular Biology, Cambridge, England, she joined the faculty of Yale University in the Department of Medical Biophysics and Biochemistry (1970). She became Professor (1978), Henry Ford II Professor (1992) and Sterling Professor (1998). She became an Investigator of the Howard Hughes Medical Institute in 1986. Prof Steitz is a member of the National Academy of Sciences and holds many awards including the Eli Lilly Award in Biological Chemistry (1976), the U.S. Steel Foundation Award in Molecular Biology (1982), the National Medal of Science (1986), the Novartis-Drew Award in Biomedical research (1999), the RNA Society Lifetime Achievement Award (2004), the E.B. Wilson Medal (2005), the Rosalind E. Franklin Award for Women in Science, National Cancer Institute (2006), and many honorary doctorates.

† 1951-2023

C. David Allis is a leader in the field of chromatin biology. He has pioneered experimental and theoretical studies elucidating the mechanisms by which post-translational modifications of histones regulate the functions of chromatin. His studies demonstrating the identity between biochemically purified histone modifying enzymes and genetically defined transcription co-activators established a critical link between covalent histone modifications and gene activation and opened a new era in chromatin biology and our understanding of genome function. He proposed and refined the current paradigm referred to as the 'histone code hypothesis' to explain how cell signaling cascades result in individual or combinatorial histone modifications, forming an epigenetic code that dictates specific functional outcomes through downstream interactions with distinct combinations of transcriptional regulatory factors. His research has been driven by his development of novel methods for studying protein modifications that are now mainstream in the field. His work has brought together the fields of chromatin biology and genome function and has had major impact on the basic fields of genetics, cell, developmental, and molecular biology with major impact for the understanding of abnormal development and cancer.

A native of Cincinnati, Ohio Dr Allis received a PhD from Indiana University (1978). Following postdoctoral studies (1978-1981) at the University of Rochester, he has held academic positions at Baylor College of Medicine as Assistant Professor (1981) to Professor (1988), Syracuse University,University of Rochester (Marie and Joseph Wilson Professor, Departments of Biology and Oncology), and the University of Virginia Health System (Harry F. Byrd Jr. Professor of Biochemistry and Molecular Genetics). Since 2002, he has been Joy and Jack Fishman Professor and Head, Laboratory of Chromatin Biology, The Rockefeller University. He has been elected to numerous prestigious societies including Phi Beta Kappa, the American Academy of Arts and Sciences, The American Academy of Microbiology, the Harvey Society, the American Society for Biochemistry and Molecular Biology, and the National Academy of Sciences. He has received numerous awards including the Syracuse University William J. Wasserman Prize, the University of Rochester Davey Award, the Baxter Award for Distinguished Research, the Massry Prize, and the John Wiley Prize, to name a few. He has presented many Distinguished Lectures, has published over 240 scientific papers, and is co-editor of a recent ground breaking book on Epigenetics.

Proper chromosome segregation during mitosis is essential for all life, and has been one of the outstanding problems in cell biology for over 100 years. Nasmyth has dominated the field of mitotic regulation with a series of incisive discoveries, including characterization of the anaphase promoting complex that degrades mitotic cyclins, the cohesin complex that links sister chromatids together prior to mitosis, and most importantly, the novel proteolytic mechanism that rapidly breaks up sister chromatid cohesion at the onset of mitosis. Nasmyth's work on fundamental aspects of cell divison has profound implications for our understanding of chromosome non-disjunction in human cancer and other genetic diseases.

Kim Nasmyth obtained his PhD from the University of Edinburgh (1977), followed by postdoctoral training with Ben Hall at the University of Washington. From 1980-81 he was a Robertson Fellow at Cold Spring Harbor Laboratory, before becoming a staff member at the Laboratory for Molecular Biology in Cambridge (1982-1987). He joined the Institute for Molecular Pathology in Vienna as a Senior Scientist in 1988 and became Director 1997. In 2005, he became Whitley Chair of the Department of Biochemistry at Oxford University.

Professor Nasmyth has won a number of career awards including the Max Perutz Prize, the FEBS Silver Medal, the Unilever Prize, the Louis Jeantet Prize, and the Wittgenstein Prize. He is a member of the European Molecular Biology Organization, a Fellow of the Royal Society, a Foreign Member of the American Academy of Arts and Sciences, and a Member of the Austrian Academy of Sciences.

Harry F. Noller's work has led to fundamental changes in our thinking about the role of RNA in the many steps of protein synthesis. He has used the full range of techniques including traditional biochemical as well as high resolution structural analysis to elucidate mechanisms of protein synthesis. His contributions to the sequencing and of genes encoding ribosomal RNAs and to phylogenetic and other analysis of these data led to insights into the secondary structure of these molecules and to functional inferences. Chemical probing and crosslinking experiments provided the key insights to appreciate the possibility that the peptidyl transferase activity of the large subunit of the ribosome may comprise RNA. His subsequent refined structural analysis building on results from biochemical analysis of stripping of proteins from the large ribosomal subunit and assaying for peptidyl transferase activity has provided a significant contribution to the full understanding of RNA catalysis of peptide bond synthesis and other aspects of ribosome structure and function and protein synthesis.

A native of Oakland, California, Harry Noller received PhD in Chemistry from the University of Oregon (1965). Following postdoctoral work at the Medical Research Council Laboratory of Molecular Biology, Cambridge and the Institute of Molecular Biology, University of Geneva, he joined the Department of Biology, University of California, Santa Cruz as Assistant Professor (1968), becoming Professor in 1979. He has been Robert L. Sinsheimer Professor of Molecular Biology since 1987 and since 1992, Director, Center for Molecular Biology. He was Sherman Fairchild Distinguished Scholar, Division of Biology, California Institute of Technology (1989-1990).

He is a member of the American Academy of Microbiology, the American Academy of Arts and Sciences, The RNA Society, The National Academy of Sciences, and The American Association for the Advancement of Science and others. He presented the Harvey Lecture at Rockefeller University (1989), and has received the Rosensteil Award in Basic Biomedical Science (2001), AAAS Newcomb Cleveland Prize (2002), Speaker of the Year, Netherlands Society for Biochemistry and Molecular Biology (2002), RNA Society Lifetime Achievement Award (2003), Massry Prize (2004), and the Paul Ehrlich and Ludwig Darmstaedter Prize (2007). He has authored or co-authored approximately 200 high impact publications and has trained many outstanding students and postdoctoral fellows.

† 1940-2018

Thomas Steitz's scientific career has involved studies of biological structure using X-ray crystallography including developing and refining novel techniques to determine the structure of proteins and nucleic acids with the focus of addressing questions of biological function and mechanism of action. Much of his work has been directed to understanding the structural basis of enzyme mechanisms and on protein-nucleic acid interactions.

His earliest studies on protein structure and mechanism of enzyme action include work on yeast hexokinase demonstrating that substrate binding induces a large conformational change in the enzyme providing experimental support for the induced fit mechanism of enzyme specificity. Subsequently, his work has focused on providing a structural basis for understanding the mechanisms and specificity of gene expression including replication, genetic recombination, transcription, reverse transcription, and translation, the work cited for this award.

He provided the first structure of a DNA polymerase, a bacterial polymerase, followed by studies on mammalian polymerases and the HIV reverse transcriptase. These studies and elucidating structures of recombination enzymes, RNA polymerases, transcription factors, and aminoacyl tRNA synthetases have all provided important and in many cases unexpected insights into biological function in pathways involved in information transfer and genome stability and change. His structural studies on the large ribosomal subunit provided the first atomic level insights into the structure and function of the ribosome, the site of protein synthesis in the cell.

Further studies have refined insights into principles of RNA folding, stability, and RNA-protein interaction, and have also addressed questions of the mechanisms of peptide bond formation and other aspects of protein synthesis on the ribosome. Structures of complexes between the large subunit and antibiotics make possible the structure-based design of new antibiotics potentially active against antibiotic resistant microorganisms.

Tom Steitz is a co-founder and Chairperson of the Scientific Advisory Board of a company involved in the translation of the basic studies of the ribosome to be applied to the development of important health care products, effective antibiotics active against presently antibiotic resistant microorganisms. Likely the most significant outcome of the studies on the ribosome from the Steitz lab is the elucidation of the chemical mechanism of RNA catalyzed peptide bond formation and the key role of RNA in ribosome structure and function; the ribosome is a ribozyme.

Dennis Slamon's work exemplifies translational research of the highest order. He has taken a basic research finding, HER2/neu oncogenes, and developed a better understanding of how this marker serves as a surrogate for prognosis, a therapeutic target, and a predictive test for therapeutic outcome. His work has saved the lives of thousands of women. Herceptin has provided a paradigm shift in the field of cancer therapy by showing that drugs can be developed against defects present in specific cancers.

Born in Pennsylvania, Dr Slamon obtained his BA at Washington & Jefferson College, and his MD from the University of Chicago (1975). He received his PhD in cell biology the same year (1975). He has spent his whole career at the UCLA School of Medicine, Los Angeles, first as a Fellow in the Division of Hematology-Oncology, Department of Medicine, (1979-81), Associate Chief (1989-1991), and as full Professor (1993). In 1994 he became Executive Vice-Chair for Research.

He is the recipient of many honours and awards, including Outstanding Young Investigator Award (Western Society of Clinical Investigation, 1988), the University of California, San Diego/Salk Translational Award (2000), the Medal of Honour for Clinical Research (American Cancer Society 2004), the David A Karnofsky Memorial Award (American Society of Clinical Oncology, 2006), and the European Institute of Oncology Breast Cancer Award (Milan, Italy 2006).

Prof. zur Hausen received his MD in 1960 from the University of Dusseldorf. After receiving further medical training, he was a research fellow first at the University of Dusseldorf 1962-1965, and then at the Children's Hospital of Philadelphia, 1966-1969, where he worked under Prof. Werner Henle. In 1969, he returned to Germany, at the University of Wurzburg, as a Senior Scientist at the Institute for Virology. During 1972-1977, he was the Chairman and Professor in the Institute for Clinical Virology at the University of Erlangen-Nurnberg, and then during 1977-1983 the Chairman and Professor at the Institute for Virology at the University of Freiburg. From 1983 until 2003, he was the Scientific Director and Chairman of the Management Board of the German Cancer Research Center (DKFZ) in Heidelberg. In 2003, he became an emeritus professor at the German Cancer Research Center. Prof. zur Hausen's laboratory has made several particularly noteworthy findings in papillomavirus research. The earliest was the recognition that there are multiple HPV genotypes, particularly that the HPVs that caused non-genital warts and those that caused genital warts might be distinct (2,3). Prior to his studies, it was believed that there might be a single HPV, as it had been shown in the first part of the 20th century that cutaneous warts could be induced with filtrates from genital or laryngeal warts.

His most important finding was the identification and molecular cloning of the HPV16 and HPV18 genomes, and the associated demonstration that a majority of cervical cancers contained DNA that hybridized under stringent conditions to probes from HPV16 or HPV18 and that an even higher proportion of cervical cancers would hybridize to these probes under less stringent conditions. These observations strongly implied: 1) papillomaviruses were etiologically involved in this cancer; 2) infection by more than one HPV type could result in cervical cancer; and 3) there were additional related HPV types that also caused cervical cancer. Indeed, subsequent research has indicated that infection by more than 10 other HPVs that are phylogenetically related to HPV16 and HPV18 are also in cervical cancer. HPV16 and 18 are the most oncogenic, accounting for about 70% of cervical cancer.The third critical finding was that the HPV DNA was integrated into the host genome in cervical cancer cell lines and the associated demonstration that the viral E6 and E7 genes were preferentially retained and expressed in the tumors. These observations provided a mechanism for the efficient transfer of viral DNA progeny cells, implied that viral gene expression might be required for maintenance of the tumorigenic phenotype, and that E6 and E7 probably represented key viral oncogenes.The findings related to HPV16 and HPV18 formed the basis for subsequent epidemiologic studies confirming that infection by a subset of HPV types, most notably HPV16 and HPV18, accounts for virtually all cervical cancers. In addition to the role of HPV in cervical cancer, other evidence has led to the conclusion that a substantial proportion of several additional types of cancer are also caused by HPV infection. These include various genital cancers (such as vulvar and penile cancers), anal cancers, and head-and-neck cancers.

Prof. zur Hausen has continued to run a highly productive laboratory since making the above seminal findings, publishing an average of more than 5 papers per year. Some of the more important findings made during this period include: 1) finding that most Buschke-Loewenstein tumors, which are large but low-grade malignant penile tumors, contain HPV6 or HPV11, which usually do not cause malignancy at other sites; determining that E6 and E7 expression in cervical cancer cell lines is required for maintaining the transformed phenotype; finding that HPV DNA in cervical tumors may be integrated near the c-Myc oncogene and be associated with its activation; the isolation of several new HPV types and their clinical importance; epidemiological studies delineating the prevalence of genital HPV infection and the risk of progression dysplasia or cancer; identification of cellular transcription factors that interact with the main HPV promoter; and the role of AP-1, Fos, and Fra-1 in regulating HPV transcription. He has also been a highly sought after and effective spokesman for the papillomavirus research community and for the role of viruses in human cancer.

Gary Ruvkun is a professor of genetics at Harvard Medical School. Dr. Ruvkun is a graduate of UC Berkeley and Harvard. His PhD thesis with Fred Ausubel explored the symbiotic nitrogen fixation genes of Rhizobium. Dr. Ruvkun began to work with C. elegans as a postdoc with Bob Horvitz at MIT and Walter Gilbert at Harvard, where he collaborated with fellow postdoctoral fellow Victor Ambros on the molecular analysis of the heterochronic genes.

The work on miRNAs and their target mRNA genes by Ambros and Ruvkun began in 1982 when they targeted the lin-14 gene for molecular analysis. The genetic analysis that Ambros and Horvitz had done suggested that the gene lin-4 negatively regulates lin-14 but the molecular basis of that regulatory axis was not known. In the Horvitz lab, Ruvkun and Ambros had to develop new technologies to allow such genetically defined loci to be analyzed molecularly, and they succeeded to isolate the lin-14 gene. This work continued in their own labs at Harvard, starting in 1984 for Ambros and 1985 for Ruvkun. The first hint that the key regulatory element of the lin-14 gene was in its 3' untranslated region came from the molecular analysis of lin-14 gain-of-function mutations, showing that they are deletions of conserved elements in the lin-14 3' untranslated region that relieve the normal late stage-specific repression of LIN-14 protein production, and showing that lin-4 is necessary for that repression. The Ambros lab discovered in 1993 that lin-4 encodes a very small RNA product. When Ambros and Ruvkun compared the sequence of the lin-4 miRNA and the lin-14 3' untranslated region, they discovered that the lin-4 RNA base pairs with conserved bulges and loops to the 3' untranslated region of the lin-14 target mRNA to downregulate its translation, and that deletions in the lin-14 3' UTR complementary sites, which are conserved in evolution, relieve the repression normally induced by base pairing to the lin-4 miRNA These papers revealed a world of RNA regulation at an unprecedented small size scale and the mechanism of that regulation.

In 2000, the Ruvkun lab, again in collaboration with the Ambros and Horvitz labs, reported in Nature the identification of second microRNA, let-7, which like the first microRNA regulates translation of the target gene lin-41 via imperfect base pairing to the 3' untranslated region of that mRNA. This was the first indication that miRNA regulation via 3' UTR complementarity was a general phenomenon.

The microRNA field was shown to be general in biology with the publication from the Ruvkun lab of a second Nature paper in 2000 reporting that the sequence and regulation of the let-7 microRNA is conserved across animal phylogeny, including in humans. Presently thousands of miRNAs have been discovered, pointing to a world of gene regulation at this size regime.

Dr. Ruvkun lab has also identified protein coding genes that constitute a genetic pathway for the regulatory function of miRNAs and siRNAs and other small RNAs. In a 2005 Nature paper, the Ruvkun lab reported that mutations in the retinoblastoma ortholog of C. elegans dramatically activates RNAi, and that cell lineage defects in animals with defective retinoblastoma could be reversed by inactivating particular RNAi pathway genes. This revealed that small RNAs are likely to mediate the dysregulations of cell cycle during tumor formation, a previously unsuspected regulatory modality in tumor formation. In addition to revealing fundamental regulatory axes in biology, some of these components may be developed as drug targets to enhance RNAi in mammals, a technical improvement that may be necessary to elevate a laboratory tool to a therapeutic modality.

Dr. Ruvkun has also worked in other fields, such as control of longevity and fat storage, where his lab discovered for example that insulin signaling is key to longevity in C. elegans. Dr. Ruvkun has an active research program in microbiology, searching for deeply divergent microbial life, even on other planets.

Victor Ambros grew up in Vermont and graduated from MIT in 1975. He did his graduate research (1976-1979) with David Baltimore at MIT, studying poliovirus genome structure and replication. He began to study the genetic pathways controlling developmental timing in the nematodeC. elegansas a postdoc in H. Robert Horvitz's lab at MIT, and continued those studies while on the faculty of Harvard (1984-1992) Dartmouth (1992-2007), and the University of Massachusetts Medical School (2008-present). In 1993, members of the Ambros lab identified the first microRNA, the product oflin-4, a heterochronic gene ofC. elegans. Since then, the role of microRNAs in development has been a major focus of his research.

Primarily a developmental biologist, Prof. Ambros is interested in the genetic regulatory mechanisms that control animal development, and in particular the molecules that function during animal development to ensure the proper timing of developmental events. He has primarily employed the nematodeCaenorhabditis elegansas a model system for studying the function of regulators of developmental timing, which inC. elegansare known as the "heterochronic genes", in reference to the remarkable changes in relative timing of developmental event that are elicited by mutations in these genes. The heterochronic genes comprise a set of interrelated regulatory pathways that include proteins that regulate the transcription of other genes, and also a class of small RNA, known as microRNAs, that regulate the production of protein by the messenger RNAs of specific target genes. Much of his research in recent years has been aimed at understanding how microRNAs are integrated into broader regulatory networks related to animal development and human disease, and at uncovering the molecular mechanisms for how microRNAs exert their effects on gene expression.

Dr. Sonenberg received his BSc and MSc (Microbiology and Immunology) from Tel-Aviv University. Upon completing his Ph.D. (Biochemistry) at the Weizmann Institute of Science (Rehovot, Israel), he joined the Roche Institute of Molecular Biology in Nutley, New Jersey with a Chaim Weizmann postdoctoral fellowship. He joined McGill University in 1979, and is currently the James McGill Professor in the Department of Biochemistry and the McGill Cancer Centre.

Dr. Sonenberg's primary research interest has been the control of protein synthesis. He identified the mRNA 5' cap-binding protein, eIF4E, in 1978. He later discovered the IRES (internal ribosome entry site) mechanism of translation initiation in eukaryotes, as well as the regulation of cap-dependent translation by the eIF4E binding proteins (4E-BPs). He also discovered that eIF4E is a proto-oncogene, levels of which are elevated in cancer, and subsequently demonstrated that rapamycin (an important anti-cancer drug) inhibits eIF4E activity. Finally, while generating 4E-BP 'knock-out' mice, he and his colleagues found that this translation inhibitor plays critical roles in the metabolism of adipose tissue, and learning and memory.

In 2002, Dr. Sonenberg was awarded the Robert L. Noble Prize from the National Cancer Institute of Canada. He is an International Research Scholar of the Howard Hughes Medical Institute, a Canadian Institutes of Health Research Distinguished Scientist and has been a fellow of the Royal Society of Canada since 1992. Dr. Sonenberg has recently been awarded the Killam Prize for Health Sciences.

Dr. Samuel Weiss is Professor and Alberta Heritage Foundation for Medical Research (AHFMR) Scientist in the Departments of Cell Biology & Anatomy and Pharmacology & Therapeutics at the University of Calgary Faculty of Medicine. He is the inaugural Director of the Hotchkiss Brain Institute, a partnership between the Faculty of Medicine and the Calgary Health Region, whose mission is to translate innovative research and education into advances in neurological and mental health care.In 1978, Dr. Weiss received his BSc in Biochemistry at McGill University and in 1983 completed his PhD in Chemistry (Specialization: Neurobiology) at the University of Calgary. Following post doctoral fellowships (1983-1988), funded by AHFMR and the Medical Research Council of Canada (MRC), at the Centre de Pharmacologie-Endocrinologie, Montpellier, France, and at the University of Vermont College of Medicine, Burlington, Vermont. Dr. Weiss was appointed Assistant Professor and MRC Scholar at The University of Calgary in 1988.

Two major discoveries are the hallmarks of Dr. Weiss' research career. In 1985, together with Dr. Fritz Sladeczek, Dr. Weiss discovered the metabotropic glutamate receptor - now a major target for pharmaceutical research and development for neurological disease therapies. In 1992, Dr. Weiss discovered neural stem cells in the brains of adult mammals. This research has lead to new approaches for brain cell replacement and repair. Dr. Weiss sits on numerous national and international peer review committees, has authored many publications, holds key patents in the neural stem cell field and has founded two biotechnology companies. In 2002, Dr. Weiss was awarded the Fondation IPSEN (France) prize in Neuronal Plasticity and in 2004 he received the Canadian Federation of Biological Societies Presidents' Award in Life Sciences Research.

Dr. Weiss' current research focuses on the cellular, molecular and in vivo biology of neural precursors, and on the direct regulation of intrinsic adult neural stem cells and functional recovery in animal models of brain and spinal cord injury or disease. Two new research avenues are directed towards: (1) elucidating the role for new adult neurons in the formation of social memories and (2) understanding adult human brain tumour stem cell biology, in particular the mechanisms of autocrine growth factor signalling that lead to uncontrolled growth.

Dr. Bernstein is currently the President of the Canadian Institute for Advanced Research (CIFAR), one of Canada’s major global research assets. From 2008-2011, Dr. Bernstein was the executive director of the Global HIV Vaccine Enterprise, an international alliance of researchers and funders charged with accelerating the search for an HIV vaccine. Previously, he served as the founding president of the Canadian Institutes of Health Research (2000-07), Canada’s federal agency for the support of health research. In that capacity, he led the transformation of health research in Canada.

After receiving his PhD from the University of Toronto, and following postdoctoral work in London, Dr. Bernstein joined the Ontario Cancer Institute (1974-1985). In 1985 he joined the new Samuel Lunenfeld Research Institute in Toronto, was named Associate Director (1988) and then Director of Research (1994-2000). The author of over 225 scientific publications, Dr. Bernstein has made extensive contributions to the study of stem cells, hematopoiesis and cancer. He is a member and/or chair of advisory and review boards in Canada, the US, UK, Italy and Australia. Dr. Bernstein has received numerous awards and honorary degrees for his contributions to science, including the 2008 Canada Gairdner Wightman Award. He is a Senior Research Fellow of Massey College and was inducted into the Order of Canada in 2002.

Inside the cell, many newly made proteins pass through a maze-like structure of membranes, where they are folded and groomed into their final shapes before being shipped to precise destinations to carry out their functions. This structure, called the endoplasmic reticulum, enforces strict quality control standards to help ensure that defective or misfolded proteins are not allowed to leave. Peter Walter expores the signaling pathway by which cells alter their quantities of endoplasmic reticulum. This communication process is so crucial to cells that imbalances can lead to a number of diseases, including cancer, diabetes, cystic fibrosis, and vascular and neurodegenerative diseases.

Growing up in his native Germany, Walter spent hours in his father's West Berlin "chemist shop," a drugstore where medicines and chemicals were mixed and sold. This exposure-along with his own dabbling in the pyrotechnical adventures of mixing chemicals-fostered Walter's early interest in science. By age 12, he knew he wanted to be a chemist. He came to Vanderbilt University as a graduate student, part of a nine-month exchange program in organic chemistry. Walter's main intent was to immerse himself in the English language, a prerequisite he thought necessary to further his research career. He quickly discovered, however, that American universities offered scientists-to-be more hands-on experience and training to eventually work as independent researchers. Walter became hooked on this style of learning and never left.

As a PhD student at the Rockefeller University in the late 1970s, Walter worked with Günter Blobel, an HHMI investigator and winner of the 1999 Nobel Prize in Physiology or Medicine for his discovery of the mechanisms that proteins use to find their correct locations within the cell. Blobel had postulated that newly synthesized proteins contain built-in signals, or address tags, that direct them to their proper destinations, but it remained unclear how the address tags were recognized. That problem was solved when Walter identified the six proteins and the small bit of RNA that make up the signal recognition particle. The identification of this particle was central to Blobel's hypothesis. To this day, Walter continues to study the signals used by proteins to ensure they are shuttled to their proper destinations.

In his laboratory at the University of California, San Francisco, Walter also has turned his attention to deciphering the pathways that cells use to regulate the abundance of their organelles. With a particular focus on the endoplasmic reticulum (ER), he has uncovered a feedback loop within cells called the "unfolded protein response." Working with yeast as a model, his pioneering studies have shown that cells need the right amount of ER to properly fold newly assembled proteins. The same principles also apply in higher organisms, including humans. "Regulating how much ER you have is a fundamental process for cells, and it is a key determinant for any number of diseases," Walter noted. "By understanding the details of this mechanism, we hope to make significant contributions to understanding many medically important pathologies."

Proteins must be correctly folded and assembled to fulfill their functions as assigned by genetic code. Unfolding or misfolding of proteins constitutes a fundamental threat to all living cells. In eukaryotes, proteins can be unfolded or misfolded in a variety of subcellular compartments, but the risk of protein misfolding is particularly acute in the endoplasmic reticulum, in which newly synthesized secretory and transmembrane proteins attain their proper tertiary structure. With their pioneering work on an intracellular signaling pathway called the 'Unfolded Protein Response', Dr. Mori, together with Dr. Walter, has elucidated the molecular mechanisms by which cells adjust their capacity for protein folding and quality control according to need. Their work provides answers to the fundamental question of how cells maintain a proper abundance of organelles and has far reaching implications for our understanding of the development of specialized cell types and various diseases, including protein folding disorders, diabetes, heart diseases, atherosclerosis and cancer.

Dr. Kazutoshi Mori is a professor at the Graduate School of Science, Kyoto University since 2003. He graduated from the Graduate School of Pharmaceutical Sciences, Kyoto University. He was Instructor at Gifu Pharmaceutical University from 1985 to 1989, and then worked as a postdoctoral fellow at the University of Texas Southwestern Medical Center at Dallas from 1989 to 1993 (under supervision from Drs. Mary-Jane Gething and Joe Sambrook). He was Deputy Research Manager from 1993 to 1996 and Research Manager from 1996 to 1999 at the HSP Research Institute in Kyoto (directed by Dr. Takashi Yura). He was Associate Professor at the Graduate School of Biostudies, Kyoto University from 1999 to 2003.

Lucy Shapiro is a Professor in the Department of Developmental Biology at Stanford University School of Medicine where she holds the Virginia and D. K. Ludwig Chair in Cancer Research and is the Director of the Beckman Center for Molecular and Genetic Medicine. She received her PhD in Molecular Biology from Albert Einstein College of Medicine. She joined the faculty of Stanford University School of Medicine in 1989 and served as the founding Chair of the Department of Developmental Biology from 1989-1997. Prior to coming to Stanford, Professor Shapiro was the Higgins Professor and Chair of Microbiology at the College of Physicians and Surgeons of Columbia University, and prior to that she held the Lola and Saul Kramer Endowed Chair at Albert Einstein College of Medicine where she was Chair of the Department of Molecular Biology.

Professor Shapiro is a member of the Board of Advisors of The Pasteur Institute, The Ludwig Institute for Cancer Research, and Lawrence Berkeley National Labs. She was a member of the Board of Directors of SmithKline Beecham, PLC, Silicon Graphics, Inc. and GlaxoSmithKline, PLC, and she currently serves on the Board of Directors of Gen-Probe, Inc. She founded the anti-infectives discovery company, Anacor Pharmaceuticals, in 2001 and is a member of the Anacor Board of Directors. Professor Shapiro has been the recipient of multiple honors, including: the FASEB Excellence in Science Award, the UC Berkeley Hitchcock Professorship, and election to the Institute of Medicine, The American Academy of Arts and Sciences, the US National Academy of Sciences, and the American Philosophical Society. She was awarded the 2005 Selman A. Waksman Award in Microbiology from the US National Academy of Sciences.

Studying the molecular mechanisms by which cells switch identity was a passion throughout Prof. Losick's career. He tackled this problem in a primitive organism, a bacterium that can either grow and divide or transform itself into a dormant cell known as a spore. Making a spore involves two cells, one that will become the spore and one that nurtures the developing spore. Prof. Losick and his colleagues discovered mechanisms by which a cell divides asymmetrically to give rise to the developing spore and the nurturing cell. They discovered an important class of regulatory proteins that controls the expression of large blocks of genes during spore formation and as we now know in many other kinds of bacteria as well. They elucidated exquisitely intricate mechanisms orchestrating the expression of hundreds of genes and ensuring that they are switched on at the right time and the right place. Dr. Losick and his colleagues also discovered that the protein products of those genes have distinctive subcellular addresses and localize in a choreographed movement, that the developing spore and the nurturing cell talk to each other in a chemical code that keeps events in one cell in register with events in the sister cell, and elucidated the molecular mechanisms by which these conversations takes place. Understanding bacteria is important to humanity because microbes are both beneficial and the causative agent of many diseases. The human body is a host to ten times more bacteria than human cells and bacteria are important agents of change in our environment and in Earth's history. Some microbes are pathogens whereas others are sources of medicines. Fundamental studies of bacteria inform efforts to combat infections and to harness the microbial world for the benefit of humanity.

Richard Losick is the Maria Moors Cabot Professor of Biology, a Harvard College Professor, and a Howard Hughes Medical Institute Professor in the Faculty of Arts & Sciences at Harvard University. He received his AB in Chemistry at Princeton University and his PhD in Biochemistry at the Massachusetts Institute of Technology. Upon completion of his graduate work, Professor Losick was named a Junior Fellow of the Harvard Society of Fellows when he began his studies on RNA polymerase and the regulation of gene transcription in bacteria. Professor Losick is a past Chairman of the Departments of Cellular and Developmental Biology and Molecular and Cellular Biology at Harvard University. He received the Camille and Henry Dreyfuss Teacher-Scholar Award, and he is a member of the National Academy of Sciences, a Fellow of the American Academy of Arts and Sciences, a Member of the American Philosophical Society, a Fellow of the American Association for the Advancement of Science, a Fellow of the American Academy of Microbiology, and a former Visiting Scholar of the Phi Beta Kappa Society. He is 2007 recipient of the Selman A. Waksman Award of the National Academy of Sciences.

Shinya Yamanaka received his MD from Kobe University in 1987 and his PhD from Osaka City University in 1993. From 1987 to 1989 he was a resident at the National Osaka Hospital. He spent the period from 1993 to 1996 as a postdoctoral fellow in the Gladstone Institute of Cardiovascular Disease, San Francisco where he served as a post-doctoral fellow with the aim of obtaining further research skill and practical field experience, he was particularly interested in production technology of knockout mouse and transgenic mouse. During his stay at the Gladstone Institute, he discovered NAT 1, which later recognized as an indispensable gene in differentiation of ES cell. He returned to Osaka City University Medical School to take an assistant professor position in 1996, and was then appointed as an associate professor at Nara Institute of Science and Technology in 1999, where he became a full professor in 2003. He moved on to take up his current position as a professor in Kyoto University in 2004. At the same time, he received an appointment as a visiting scientist at the Gladstone Institute in 2007. Having successfully established induced pluripotent stem cell or iPS cell, he was appointed as Director for CiRA, Center for iPS Cell Research and Application at Kyoto University in 2008. He is now actively conducting iPS cell research with two dozens of researchers and students toward regenerative medicine.

Nubia graduated from the School of Medicine at Universidad del Valle in 1964. After graduation from Universidad del Valle, she worked for three years in the National Cancer Institute in Bethesda, where the headquarters of the National Health Institute is located. She got a Master's Degree in Public Health specializing in Epidemiology and Virology of Cancer in the School of Public Health of Johns Hopkins University in Baltimore. Then, she went to Lyon, France, to continue her research at the International Agency for Research of Cancer (IARC), which belongs to the World Health Organization.

Nubia Muñoz is a former winner of the First Richard Doll Prize in Epidemiology for proving that HPV causes cervical cancer. Her story is a remarkable one and will undoubtedly go down in the annals of epidemiology as an example par excellence of what all epidemiologists aspire to and can accomplish in studying the etiology of a disease.

Nubia Muñoz was a Postgraduate student, School of Public Health, 1968 to 1969, at Johns Hopkins. Nubia Munoz' work at the International Agency for Research on Cancer in Lyon, France, and with teams across the world led to establishing the relationship between the human papillomavirus and cervical cancers. This recognition of a viral cause of cervical cancer has led to the development of vaccines that would prevent these infections and that hold promise for the control and possible elimination of this cancer.

Nubia Muñoz was inducted in the Johns Hopkins Society of Scholars in 2004. This induction is to honor the significant accomplishments of men and women who spent part of their careers at Johns Hopkins. The society - the first of its kind in the USA - inducts former postdoctoral fellows and junior or visiting faculty at Johns Hopkins who have gained marked distinction in their fields of physical, biological, medical, social or engineering sciences or in the humanities and for whom at least five years have elapsed since their last Hopkins affiliation.

† 1934-2015

After training in internal medicine, nephrology and epidemiology Dave Sackett’s first career (age 32) was as the founding Chair of Clinical Epidemiology & Biostatistics at McMaster. In his second career he began to design, execute, interpret, monitor, write and teach about randomized clinical trials, an activity that continues to the present, some 200 trials later. His third career was dedicated to developing and disseminating “critical appraisal” strategies for busy clinicians , and ended when he decided he was out of date clinically and returned (at age 49) to a two-year “retreading” residency in Hospitalist Internal Medicine. His fifth career (and the only one he didn’t enjoy) was as Physician-in-Chief at Chedoke-McMaster Hospitals. His sixth career was as Head of the Division of General Internal Medicine for Hamilton and Attending Physician at the Henderson General Hospital. When a chair was created for him at Oxford, he took up his seventh career as foundation Director of the NHS R&D Centre for Evidence-Based Medicine, Consultant on the Medical Service at the John Radcliffe Hospital, Foundation Chair of the Cochrane Collaboration Steering Group, and Foundation Co-Editor of Evidence-Based Medicine. Retired from clinical practice at age 65, he began his eighth career by returning to Canada and setting up the Trout Research & Education Centre, where he reads, researches, writes and teaches about randomized clinical trials. Along the way, he has published 10 books, chapters for about 50 others, and about 300 papers in medical and scientific journals.

Peter J. Ratcliffe was educated at Lancaster Royal Grammar winning an open scholarship to Gonville and Caius College, Cambridge in 1972. He studied Medicine at Cambridge and St Bartholomew's Hospital, London graduating with Distinction in 1978. He trained in renal medicine at Oxford initially working on the physiology of renal oxygenation and its implications for renal injury in shock.

In 1989 he changed fields to found a new laboratory, obtaining a Senior Fellowship from the Wellcome Trust to work on cellular oxygen sensing pathways. Over 20 years he has led the 'oxygen sensing' group successively in the Weatherall Institute of Molecular Medicine, the Henry Wellcome Building for Genomic Medicine, and the Henry Wellcome Building for Molecular Physiology at Oxford University. He was appointed University Lecturer in 1992, and titular Professor in 1996. He was elected Nuffield Professor of Medicine in 2003, and appointed Head of the Department of Medicine in 2004.

Awards include the Milne-Muerke Foundation Award, 1991; the Graham Bull Prize, 1998; the International Society for Blood Purification Award, 2002 and the Louis Jeantet Prize for Medicine 2009.

He was elected to the Fellowship of the Academy of Medical Sciences and to the Fellowship of the Royal Society in 2002; to EMBO in 2006 and Foreign Honorary Member of the American Academy of Arts and Sciences in 2007.

Dr. Semenza received undergraduate training (A.B.) in Biology at Harvard College; MD and PhD degrees from the University of Pennsylvania; Pediatrics residency training at Duke University Medical Center; and postdoctoral training in Medical Genetics at The Johns Hopkins University School of Medicine, where he has spent his entire career. He is currently the C. Michael Armstrong Professor at Johns Hopkins with appointments in Pediatrics, Medicine, Oncology, Radiation Oncology, Biological Chemistry, and the McKusick-Nathans Institute of Genetic Medicine.

Since 2003 he has served as Founding Director of the Vascular Program in the Johns Hopkins Institute for Cell Engineering. Dr. Semenza's laboratory identified hypoxia-inducible factor 1 (HIF-1), a transcription factor that allows cells to respond to changes in oxygen availability. The purification of HIF-1 and isolation of its coding sequences in 1995 opened the field of oxygen biology to molecular analysis and has revealed major roles for HIF-1 in many developmental, physiological, and pathological processes including cardiovascular disease and cancer. Dr. Semenza serves on the editorial boards of Antioxidants and Redox Signaling, Cancer Research, Cardiovascular Research, Circulation Research, Experimental Physiology, Journal of Clinical Investigation, Molecular and Cellular Biology, Molecular Cancer Therapeutics, and Oncogene.

He is Editor-in-Chief of the Journal of Molecular Medicine. He has been elected to the Society for Pediatric Research, American Society for Clinical Investigation, Association of American Physicians, and the National Academy of Sciences, USA.

A native of Rhode Island, Dr. William A. Catterall received his BA degree in Chemistry from Brown University in 1968, his PhD in Physiological Chemistry from Johns Hopkins School of Medicine in 1972, and his postdoctoral training in neurobiology and molecular pharmacology as a Muscular Dystrophy Association Research Fellow with Dr. Marshall Nirenberg at the National Institutes of Health from 1972 to 1974. Following three more years as a staff scientist at the National Institutes of Health, he joined the faculty of the University of Washington School of Medicine in 1977 as an associate professor in the Department of Pharmacology, became professor in 1981, and Chair of the Department of Pharmacology in 1984.

After establishing his laboratory at the University of Washington, Dr. Catterall and his colleagues discovered the voltage-gated sodium and calcium channel proteins, which are responsible for generation of electrical signals in the brain, heart, skeletal muscles, and other excitable cells. Their subsequent work has contributed much to understanding the structure, function, regulation, and molecular pharmacology of these key cell-signaling molecules. Dr. Catterall's recent work has turned toward understanding diseases caused by impaired function and regulation of voltage-gated ion channels, including epilepsy and periodic paralysis.

Dr. Catterall's early research was recognized with the Passano Foundation Young Scientist Award in 1981 and with Jacob Javits Neuroscience Investigator Awards in 1984 and 1991. Dr. Catterall received the Basic Science Prize of the American Heart Association in 1992, the Mathilde Solowey Award in Neuroscience from the National Institutes of Health and the H.B. Van Dyke Award in Pharmacology from Columbia University in 1995, the McKnight Foundation Senior Neuroscience Investigator Award in 1998, and the Bristol-Myers Squibb Award for Distinguished Achievement in Neuroscience Research in 2003.

Dr. Catterall was elected to the National Academy of Sciences in 1989, where he served as Chair of the Section of Physiology & Pharmacology from 1998 to 2001. He was elected to the Institute of Medicine and the American Academy of Arts & Sciences in 2000, and he was elected as a Foreign Member of the Royal Society of London in 2008. He served as editor-in-chief of Molecular Pharmacology from 1985 to 1990, was a founding member of the editorial board of Neuron in 1988, and has been an editorial board member of numerous other professional journals. Dr. Catterall and his colleagues have published more than 400 research papers and 30 reviews and reference works on voltage-gated ion channels.

Dr. Pierre Chambon is Honorary Professor at the College de France (Paris), and Emeritus Professor at the Faculté de Médecine of the Strasbourg University. He was the Founder and former Director of the IGBMC, and also the Founder and former Director of the Institut Clinique de la Souris (ICS/MCI), in Strasbourg.

Dr. Pierre Chambon is a world expert in the fields of gene structure, and transcriptional control of gene expression. During the last 25 years his studies on the structure and function of nuclear receptors has changed our concept of signal transduction and endocrinology. By cloning the estrogen and progesterone receptors, and discovering the retinoic acid receptor family, he markedly contributed to the discovery of the superfamily of nuclear receptors and to the elucidation of their universal mechanism of action that links transcription, physiology and pathology. Through extensive site-directed mutagenesis and genetic studies in the mouse, Pierre Chambon has unveiled the paramount importance of nuclear receptor signaling in embryonic development and homeostasis at the adult stage. The discoveries of Pierre Chambon have revolutionized the fields of development, endocrinology and metabolism, and their disorders, pointing to new tactics for drug discovery, and finding important applications in biotechnology and modern medicine.

These scientific achievements are logically inscribed in an uninterrupted series of discoveries made by Pierre Chambon over the last 45 years in the field of transcriptional control of gene expression in higher eukaryotes: discovery of PolyADPribose (1963), discovery of multiple RNA polymerases differently sensitive to a-amanitin (1969), contribution to elucidation of chromatin structure: the Nucleosome (1974), discovery of animal split genes (1977), discovery of enhancer elements (1981), discovery of multiple promoter elements and their cognate factors (1980-1993).

Pierre Chambon has received numerous international awards, including the 2004 Lasker Basic Medical Research Award for the discovery of the superfamily of nuclear hormone receptors and the elucidation of a unifying mechanism that regulates embryonic development and diverse metabolic pathways. He is a member of the French Académie des Sciences, and also a Foreign Member of the National Academy of Sciences (USA) and of the Royal Swedish Academy of Sciences. Pierre Chambon serves on a number of editorial boards, including Cell, and Molecular Cell. Pierre Chambon is author of more than 900 publications. He has been ranked fourth among most prominent life scientists for the 1983-2002 period.

Dr. Stiller is Professor Emeritus, of the University of Western Ontario in the Departments of Medicine and Microbiology and Immunology. Dr. Stiller established the Multi-Organ Transplant Service in London, Ontario, and served as the unit's chief until 1996. During this period, he was principal investigator of the Canadian multi-centre study that established the importance of cyclosporine in transplantation and led to its worldwide use as first-line therapy for transplant rejection. He was the first to demonstrate the efficacy of immunosuppression in newly diagnosed Type 1 Diabetes, establishing the human disease as an immune disorder. He has published over 250 Scientific Papers.

Dr. Stiller is the co-founder of two healthcare funds including the Canadian Medical Discoveries Fund Inc., where he served as Chairman and Chief Executive Officer. He was a Member of the Council and Executive Committee of the Medical Research Council of Canada (1987-1993), was the Founding Chair of the Ontario Research and Development Challenge Fund, is Chair (and co-founder) of the Ontario Institute for Cancer Research and of the Ontario Innovation Trust.

Dr. Stiller serves on the Board of Directors of several Public endeavours and foundations and is Co-founder and Director of MaRS Discovery District. He is also the recipient of numerous awards including the MEDEC Award (1992), the Order of Canada (1995) and the Order of Ontario (2000). He has received three Honorary Doctorates from McMaster University, University of Saskatchewan and University of Western Ontario. He will be inducted into the Canadian Medical Hall of Fame in 2010.

Professor White graduated from Guy’s Hospital Medical School in London and training in internal medicine in several London teaching hospitals and the Radcliffe Infirmary, Oxford. In 1980 he went to Thailand to join a research collaboration between the Faculty of Tropical Medicine, Mahidol University and the Nuffield Department of Medicine, University of Oxford. In 1986, he took over as director of this unit and later opened sister units in Vietnam (1991) and Laos (1999). These units are at the forefront of clinicial research on malaria, meliodosis, typhoid, tetanus, dengue, central nervous system infections, rickettsial diseases, and avian influenza.

William G. Kaelin Jr. is a Professor in the Department of Medicine at the Dana-Farber Cancer Institute and at the Brigham and Women's Hospital, Harvard Medical School, where he currently serves as Associate Director, Basic Science, for the Dana-Farber/Harvard Cancer Center. He obtained his undergraduate and MD degrees from Duke University and completed his training in internal medicine at the Johns Hopkins Hospital, where he served as chief medical resident. He was a clinical fellow in medical oncology at the Dana-Farber Cancer Institute and later a postdoctoral fellow in the laboratory of David Livingston, during which time he was a McDonnell Scholar.

Dr. Kaelin is a member of the American Society of Clinical Investigation and the American College of Physicians. He recently served on the National Cancer Institute Board of Scientific Advisors, the AACR Board of Trustees, and the Institute of Medicine National Cancer Policy Board. He is a recipient of the Paul Marks Prize for cancer research from the Memorial Sloan-Kettering Cancer Center, the Richard and Hinda Rosenthal Prize from the AACR, and a Doris Duke Distinguished Clinical Scientist award. In 2007 he was elected to the Institute of Medicine.

A Howard Hughes Medical Investigator since 1998, Dr. Kaelin's research seeks to understand how, mechanistically, mutations affecting tumor-suppressor genes cause cancer. His laboratory is currently focused on studies of the VHL, RB-1, and p53 tumor suppressor genes. His long-term goal is to lay the foundation for new anticancer therapies based on the biochemical functions of such proteins. His work on the VHL protein helped to motivate the eventual successful clinical testing of VEGF inhibitors for the treatment of kidney cancer. Moreover, this line of investigation led to new insights into how cells sense and respond to changes in oxygen, and thus has implications for diseases beyond cancer, such as anemia, myocardial infarction and stroke.

The challenge: To find an effective treatment for diarrheal diseases, which cause 1.3 million childhood deaths each year.

The work: Through studying the interaction of infectious diseases and nutrition, Black discovered that introducing zinc replenishment could both treat and prevent diarrhea.

Why it matters: Zinc replacement in childhood diarrhea is now the standard WHO and UNICEF recommended treatment.

Bio
Robert E. Black, MD, MPH is the Edgar Berman Professor and Chair of the Department of International Health and Director of the Institute for International Programs of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. He trained in medicine, infectious diseases and epidemiology and has served as a medical epidemiologist at the Centers for Disease Control. Dr. Black has worked at institutions in Bangladesh and Peru on research related to childhood infectious diseases and nutritional problems.

Dr. Black’s current research includes field trials of vaccines, micronutrients and other nutritional interventions, effectiveness studies of health programs (such as the Integrated Management of Childhood Illness approach), and evaluation of preventive and curative health service programs in low- and middle-income countries. His other interests are related to the use of evidence in policy and programs, including estimates of burden of disease, the development of research capacity and the strengthening of public health training.

As a member of the US Institute of Medicine, advisory bodies of the World Health Organization, and the International Vaccine Institute, among others, Dr. Black assists with the development of policies to improve child health. He currently chairs the Child Health Epidemiology Reference Group and the Child Health and Nutrition Research Initiative. He has projects in Bangladesh, Benin, Ghana, India, Mali, Pakistan, Peru, Senegal, Zanzibar and Zimbabwe. He has submissions in more than 450 scientific journal publications and is co-editor of the textbook “International Public Health.”

The challenge: To find out what the natural immune response is that recognizes foreign bacteria and viruses.

The work: Toll like receptors in the body’s cells sense microbes and mobilize the immune system to fight infection and develop long-term immunity.

Why it matters: The work leads to the development of medicines and therapies for cancer, allergies, autoimmune diseases and septic shock.

Bio
Shizuo Akira received his MD from Osaka University in 1977. After three years’ clinical training, he entered the Graduate School of Medicine, Osaka University, where he obtained his PhD in 1984. He spent two years (1985-87) as a postdoctoral fellow at the Department of Microbiology and Immunology, University of California at Berkeley. He was a research associate (1987- 1995) at the Institute for Molecular and Cellular Biology, Osaka University in the laboratory of Dr. Tadamitsu Kishimoto, where he cloned two transcription factors, NF-IL6(C/EBPbeta) and STAT3. In 1996 Dr. Akira became a professor in the Department of Biochemistry, Hyogo College of Medicine. In 1999 he was appointed as a professor of the Research Institute of Microbial Diseases, Osaka University. Since 2007, he has been a Director of WPI Immunology Frontier Research Center, Osaka University.

Dr. Akira is a member of the National Academy of Sciences and the European Molecular Biology Organization. He has received a number of prestigious awards including the Robert Koch Prize, the William B. Coley Award, and the Keio International Medical Science Prize.

The challenge: To find out what the natural immune response is that recognizes foreign bacteria and viruses.
The work: Toll like receptors in the body’s cells sense microbes and mobilize the immune system to fight infection and develop long-term immunity.
Why it matters: The work leads to the development of medicines and therapies for cancer, allergies, autoimmune diseases and septic shock.

Bio
Jules Hoffmann was born in Luxembourg and received his PhD (1969) in Biology from the University of Strasbourg. He has held various positions with the French National Research Agency (CNRS), most recently that of Distinguished Class Research Director and Member of the Board of Administration. He also serves as an Invited Professor at the University of Strasbourg. He was Director of the CNRS Institute of Molecular and Cellular Biology in Strasbourg (1993-2005).

Dr. Hoffmann’s research has focused on the development and the defence reactions of insects. Since 1990, he and his laboratory have explored the potent antimicrobial mechanisms of Drosophila as a paradigm for innate immune defences. In particular, the group is credited with having unravelled the role of Toll receptors in fighting infections.

A Member of the French National Academy of Sciences, Dr. Hoffmann served as President from 2007-08. He is a Member of the European Molecular Biology Organization (EMBO) and the German National Academy of Sciences Leopoldina. Dr. Hoffmann is a Foreign Associate of the US National Academy of Sciences, the American Academy of Arts and Sciences, and the Russian Academy of Sciences. He is the recipient of the Alexander von Humbold Price, the William B. Coley Award, the Robert Koch Prize, the Balzan Prize, the Lewis Rosenstiel Prize and the Keio Prize for Medical Sciences.

The challenge: How do cells know which genes to use and which to ignore?
The work: Aharon Razin – along with Howard Cedar and Adrian Bird – demonstrated how adding a simple chemical group (a methyl group) to DNA affects how and when genetic information is used.
Why it matters: Understanding how to turn methylation on and off could lead to treatments for cancer and other diseases.

Bio
Prof. Aharon Razin received his BSc from the Hebrew University in 1962 and went on to earn an MSc and PhD in the laboratory of Prof. Yaakov Mager on the subject of nucleotide metabolism. He did postdoctoral research in the laboratory of Dr. Robert Sinsheimer and, since 1971, has been on the faculty of the Hebrew University, where he is currently a full professor in Biochemistry. Prof. Razin is an elected member of EMBO, received the Israel Prize in 2004, and became a member of the Israel Academy of Sciences in 2008. He received the Wolf Prize in Medicine in 2008 and the Emet Prize in Life Sciences in 2009.

The challenge: How do cells know which genes to use and which to ignore?
The work: Howard Cedar – along with Aharon Razin and Adrian Bird – demonstrated how adding a simple chemical group (a methyl group) to DNA affects how and when genetic information is used.
Why it matters: Understanding how to turn methylation on and off could lead to treatments for cancer and other diseases.

Bio
Prof. Howard Cedar was born in New York in 1943. He received his BSc in Mathematics from M.I.T. and went on to do an MD and PhD in microbiology under the tutelage of Dr. James Schwartz at N.Y.U., graduating in 1970. He carried out postdoctoral research with Dr. Eric Kandel at N.Y.U. and then with Dr. Gary Felsenfeld at the N.I.H. in the framework of the Public Health Service. In 1973 he emigrated to Israel where he joined the faculty of the Hebrew University, becoming a full professor in 1981. Prof. Cedar is the recipient of the Hestrin Award for Biochemistry (1979) and the Hebrew University Outstanding Investigator Award (1991). He was elected to EMBO in 1982, received the Israel Prize in 1999 and became a member of the Israel Academy of Sciences in 2003. He received the Wolf Prize in Medicine in 2008 and the Emet Prize in Life Sciences in 2009. Three of his students have independently won the prestigious GE-Science Prize for the best doctoral work in the world.

The challenge: How does our internal biological clock control the timing of our bodies throughout the day?

The work: With Drs. Michael Rosbash and Jeffrey Hall, Young discovered that our circadian clocks are regulated by a small group of genes that work at the level of the individual cell. Subtle mutations in any of these genes can accelerate or slow our daily rhythms.

Why it matters: Their discoveries about the biological clock have applications for sleep and appetite disorders. There are also applications for organs such as the brain, liver, lungs and skin, which use the same genetic mechanisms to control their rhythmic activities.

Bio
Dr. Young received his PhD in genetics from the University of Texas (1975). He did postdoctoral work at Stanford before moving to Rockefeller. In 1991 he became head of the Rockefeller unit for the National Science Foundation's Science and Technology Center for Biological Timing. He was appointed Vice President Academic Affairs (2004) and was named Richard and Jeanne Fisher Professor the same year.

His work at Rockefeller has focused on two areas: neuromuscular development – stemming from the laboratory's isolation and study of the Notch locus of Drosophila – and the genetics of behavior, particularly circadian rhythms (including initial cloning of the period gene of Drosophila, discovery and functional characterizations of the circadian clock genes timeless, double-time, shaggy, vrille, and pdp1, and modeling of principal molecular features of the Drosophila circadian system).

Dr. Young was an investigator at the Howard Hughes Medical Institute (1987-1996) and is a member of the National Academy of Sciences and a Fellow of the American Academy of Microbiology. Among Dr. Young's awards are the 2009 Neuroscience Prize of the Peter and Patricia Gruber Foundation and the 2011 Louisa Gross Horwitz Prize of Columbia University.

The challenge: How does our internal biological clock guide our bodies throughout the day?

The work: Along with Drs. Jeffrey Hall and Michael Young, Rosbash discovered that our circadian clocks are regulated by a small group of genes that work at the level of the individual cell. Subtle mutations in any of these genes can accelerate or slow our daily rhythms.

Why it matters: Their discoveries about the biological clock have applications for sleep and appetite disorders. There are also applications for organs such as the brain, liver, lungs and skin, which use the same genetic mechanisms to control their rhythmic activities

Bio
Michael Rosbash was instrumental in revealing the molecular basis of circadian rhythms, the built-in biological clock that regulates sleep and wakefulness, activity and rest, hormone levels, body temperature, and other functions. Using the fruit fly Drosophila, he identified genes and proteins involved in regulating the clock and proposed a theory of how the clock works. Rosbash's discoveries apply to humans and other mammals, and they could ultimately lead to the development of drugs to treat insomnia, jet lag, and other sleep disorders.

After Rosbash came to Brandeis, he became increasingly interested in the influence of genes on behavior. In 1974 he began working with Jeffrey Hall, and in 1984 they cloned the period gene. Several years later, they proposed a mechanism by which a molecular 24-hour clock might work: a transcriptional negative-feedback loop. Their model still holds up, despite discoveries of additional circadian rhythm genes. In essence, the genes that are part of this loop activate the production of key proteins until a critical activity of each accumulates and turns off transcription.

The challenge: Antibodies work in the immune system to defend against bacteria and viruses. But antibodies can also trigger diseases such as arthritis and lupus.

The work: Dr. Ravetch discovered how antibodies can trigger different outcomes by binding to molecules (called Fc receptors) to change their activity. The Fc receptor allows antibodies to defend against toxins, bacteria and viruses.

Why it matters: The discovery of the Fc Receptor has changed how we think about the immune system by explaining the receptor’s puzzling dual nature as both protective and harmful. This knowledge paves the way to developing new therapies to fight autoimmune diseases such as lupus, arthritis and cancer.

Bio
Jeffrey V. Ravetch, received his training at the Rockefeller University – Cornell Medical School MD/PhD program. He earned his doctorate in 1978 in genetics with Norton Zinder and Peter Model, investigating the genetics of viral replication and gene expression for the single stranded DNA bacteriophage f1. In 1979 he earned his MD from Cornell University Medical School. He continued his training as fellow at the NIH (pursuing postdoctoral studies with Phil Leder), where he identified and characterized the genes for human antibodies and the DNA elements involved in switch recombination. From 1982 to 1996, Dr. Ravetch was a member of the faculty of Memorial Sloan-Kettering Cancer Center and Cornell Medical College. His laboratory has focused on the mechanisms by which antibodies mediate their diverse biological activities in vivo – establishing the pre-eminence of FcR pathways in inflammation and tolerance and describing novel inhibitory signalling pathways to account for the paradoxical roles of antibodies as promoting and suppressing inflammation.

Dr. Ravetch has received numerous awards, including the Burroughs-Wellcome Scholar Award, the Pew Scholar Award, the Boyer Award, the NIH Merit Award, the Lee C. Howley, Sr. Prize, the AAI-Huang Foundation Meritorious Career Award and the William B. Coley Award. He has presented numerous named lectures including the Kunkel Lecture, the Ecker Lecture, the Goidl Lecture, the Grabar Lecture and the Dyer Lecture. He was elected to the National Academy of Sciences in 2006 and to its Institute of Medicine in 2007. In 2008 he was elected a Fellow of the American Academy of Arts and Sciences. In 2009 he became a Fellow of the American Association for the Advancement of Science.

The challenge: The nervous system sends signals from our brain to different parts of our body via circuits. This allows us to see, move and process thoughts. However, accidental paralysis or neurodegenerative diseases interrupt these circuits.

The work: Dr. Jessell discovered the genetic and molecular pathways that lead to the complex development of the spinal cord. This enhances our understanding of how our nervous system communicates.

Why it matters: By understanding how sensory neurons and motor neurons communicate, we can fix the broken circuits and treat or cure traumatic damage caused by disease like ALS, stroke or spinal cord injury.

Bio
Tom Jessell was Claire Tow Professor in the Departments of Neuroscience, and Biochemistry and Molecular Biophysics at Columbia University. He was also Co-Director of the Kavli Institute for Brain Science and the Mind Brain Behavior Initiative. Between 1985-2018 Tom Jessell was an Investigator at the Howard Hughes Medical Institute.

Dr. Jessell is a Fellow of the Royal Society and the UK Academy of Medical Sciences, a Foreign Associate of the US National Academy of Sciences, and a member of the Institute of Medicine. In 2008, Jessell was co-recipient of the inaugural Kavli Prize in Neuroscience. He has also received many other awards.

† 1951-2019

The challenge: How does our internal biological clock guide our bodies throughout the day?

The work: With Drs. Michael Rosbash and Michael Young, Dr. Hall discovered that our circadian clocks are regulated by a small group of genes that work at the level of the individual cell. Subtle mutations in any of these genes can accelerate or slow our daily rhythms.

Why it matters: Their discoveries about the biological clock have applications for sleep and appetite disorders. There are also applications for organs such as the brain, liver, lungs and skin, which use the same genetic mechanisms to control their rhythmic activities.

Bio
Jeffrey Hall received a PhD in genetics from the University of Washington and was appointed to the Faculty of Brandeis University from 1974-2007. Throughout his research career, Hall has focused on the genetics of Drosophila. He worked in the laboratories of his undergraduate advisor, Philip Ives; graduate advisor, Laurence M. Sandler; and post-doctoral advisor at the California Institute of Technology, Seymour Benzer (the first to show that genes dictate the day-night cycle of activity in fruit flies). In particular, Hall has focused on the neurobiological basis of courtship behavior in Drosophila.

Dr. Hall is a member of the American Academy of Arts & Sciences and the National Academy of Sciences. He was awarded the Genetics Society of America medal (2003) and the 2009 Peter and Patricia Gruber Foundation Neuroscience Prize, both with Michael Rosbash and Michael Young.

The challenge: Meningitis, pneumonia and malaria – all dictated by seasonal climate – kill millions of children in the developing world each year.

The work: Malaria is widespread during the rainy season. Greenwood demonstrated the value of insecticide-coated bed nets and drug therapy in preventing malaria. Pneumonia and meningitis are most prevalent during the dry season. Greenwood developed and tested two groups of vaccines against these infections, which have been highly effective in saving children’s lives.

Why it matters: Dr. Greenwood has been a tireless advocate of children’s health in developing countries by battling the spread of disease and training post-doctoral scientists in Africa.

Bio
Brian Greenwood studied medicine at Cambridge (1962) followed by three years in Western Nigeria at University College Hospital, Ibadan. After further training in clinical immunology in Britain, he returned to Nigeria (1970) to help establish a new medical school at Ahmadu Bello University, Zaria. There he continued his research in malaria and meningococcal disease.

Greenwood spent 15 years directing the UK Medical Research Council Laboratories in The Gambia (1980-95). He helped to establish a multi-disciplinary research program focused on the most prevalent infectious diseases: malaria, pneumonia, measles, meningitis, hepatitis and HIV2. Greenwood demonstrated the efficacy of insecticide-treated bed nets in preventing malaria deaths in children, and demonstrated the impact of Haemophilus influenzae type b and pneumococcal conjugate vaccines in Sub-Saharan Africa.

In 1996 Dr. Greenwood joined the London School of Hygiene & Tropical Medicine where he is now Manson Professor of Clinical Tropical Medicine. He directed the Gates Malaria Partnership (2001-09) and, in 2008, became director of the Malaria Capacity Development Consortium, which supports malaria training-programs in five Sub-Saharan universities. He is also director of a consortium that studies the epidemiology of meningococcal infection in Africa prior to the introduction of a new conjugate vaccine.

The challenge: To reduce the rate of death and disease in humans and animals by building the intellectual and physical infrastructure to create new vaccines that attack infectious diseases.

The work: Dr. Babiuk connected two targets of research usually addressed separately: animals and humans. He identified a vaccine to control diarrhea from rotavirus in calves, which was then developed into a human vaccine. He was also a driving force in developing VIDO, an international vaccine facility in Saskatoon.

Why it matters: One third of all human deaths are caused by infectious disease. About 70% of the new diseases that have emerged in the last 30 years are transmitted from animals to humans. These include Mad Cow Disease, SARS, and the E.coli water contamination in Walkerton, Ontario.

Bio
Lorne A Babiuk received his PhD (1972) from the University of British Columbia. He joined the University of Alberta as Vice-President (Research) in 2007. Prior to moving to the University of Alberta, he spent 34 years at the University of Saskatchewan where he was responsible for building the successful research institution VIDO (Vaccine and Infectious Disease Organization). Under Lorne Babiuk’s leadership, VIDO became internationally recognized as a leader in novel vaccine development. While at VIDO, Babiuk completed its $19.4 million expansion (in 2005) and obtained funding for InterVac, its $140 million level-three biocontainment facility for work on infectious diseases (opened September, 2011).

In addition to being the Vice-President (Research) and former Director of VIDO, Lorne Babiuk has published over 500 peer-reviewed manuscripts and 100 essays and reviews, primarily in virology and immunology. His most recent focus has been on vaccine formulation and delivery. He is a fellow of the Infectious Disease Society of America, the Royal Society of Canada and the European Academy of Sciences as well as an Officer of the Order of Canada.

The challenge: According to Health Canada, more than 700,000 Canadians have been diagnosed with Chronic Obstructive Pulmonary Disease (COPD). Thousands more have the disease, but have not been diagnosed. There is currently no cure for COPD.

The work: Dr. Hogg’s early work with the late Dr. Peter Macklem at the Meakins Christie laboratories at McGill University established the small airway in the lung to be the obstruction site in COPD. This work has led to the current concept that this airway is a silent zone where the disease can accumulate over many years, unnoticed by COPD sufferers or their physicians. Dr. Hogg, along with his colleague Dr. Peter Pare, led the establishment of the University of British Columbia Pulmonary Research Laboratory at St. Paul’s Hospital, which now houses more than 200 staff, post graduate, graduate and undergraduate students. His work also led to a collaborative study with Dr. Avrum Spira of Boston University, uncovering a gene expression signature for the emphysematous destruction of the lung in COPD. This research also suggests that the gene expression could be reversed by a small tripeptide found in human blood, paving the way for a potential cure.

Why it matters: Dr. Hogg's research, achieved over a 40 year career, continues to have a fundamental impact on the medical community's knowledge of the pathogenesis, diagnosis and treatment of COPD. Recent results suggest a new direction which could lead to a treatment capable of reversing emphysematous destruction of lung tissue in COPD. Moreover his work stresses the importance of finding a way to diagnose COPD before symptoms appear, allowing for potential prevention of the disease. In addition to his own work, Dr. Hogg has made major contributions to building the Canadian research community locally and nationally. He has also made international contributions in the evaluation of research.

Bio
Dr. Hogg completed his medical degree at the University of Manitoba in 1962, his master's degree in experimental medicine from McGill University in 1967, and his Ph.D. in experimental medicine from McGill University in 1969. Throughout his career, Dr. Hogg's research has remained focused on the mechanisms and anatomical sites of obstructive lung disease. Dr. Hogg's research has advanced the knowledge of how the lung works in health and disease, including the pathophysiology of asthma and the harmful effects of smoking and pollution. In 1977, Dr. Hogg was recruited to the University of British Columbia and St. Paul's Hospital, where he built a world-renowned centre for pulmonary and cardiovascular research, which grew from one trainee each year to approximately 100 each year. This laboratory is currently named The University of British Columbia James Hogg Research Centre for Cardiovascular and Pulmonary Research in his honour. An Officer of the Order of Canada (2005), Dr. Hogg was elected to the Royal Society of Canada (1992) and Canadian Medical Hall of Fame (2010) and has been recognized with an array of scientific awards. In 2003, he was the recipient of the American Society for Investigative Pathology Chugai Award and has been honoured by the American Thoracic Society on several occasions. Dr. Hogg's career work in pathology, pulmonary physiology and molecular biology has leveraged over 40 years of contributions to the world's understanding of lung disease. He has arguably had a greater influence on the medical community's knowledge of Chronic Obstructive Pulmonary Disease and asthma than any other individual worldwide.

The challenge: Sexually transmitted diseases (STDs) and HIV/AIDS are among the leading causes of morbidity and mortality in many developing countries worldwide. In the early 1960s there were approximately six STDs described in textbooks and very little research was happening in sexually transmitted infections. In fact, there were not many medical centers where clinical care was offered for patients with STDs, who were left with few resources.

The work: Dr. Holmes’ career has been dedicated to the study of sexually transmitted diseases. His 45 years of cutting edge research and application of epidemiological, clinical, laboratory, and behavioural science to the study of STDs has expanded the scope of this field tremendously. Numerous clinical trials conducted by Dr. Holmes led to many diagnostic tests and standard-of-care therapies used today to treat and prevent such conditions as human papilloma virus (HPV), gonorrhea, chlamydial infections, and genital herpes, to name a few.

Why it matters: Today, over 35 have been discovered, with Dr. Holmes and his mentees working on approximately 20 of these. Dr. Holmes assisted in defining the causes of many major diseases and through leading numerous clinical trials, has paved the way for many standard-of-care therapies used to treat STDs today.

Bio
Dr. King Holmes is the William H. Foege Chair of Global Health at the University of Washington, a position he has held since 2006. He is also founder and director of the University of Washington Center for AIDS and STD, a World Health Organization Collaborating Center for AIDS and STD. Currently, Dr. Holmes is also the head of Infectious Diseases at Harborview Medical Center. Dr. Holmes completed his undergraduate degree at Harvard College in 1959, his medical degree at Cornell University Medical College in 1963 and received his Ph.D. in Microbiology from the University of Hawaii in 1967. Dr. Holmes has been a member of the University of Washington faculty since 1969, holding educational leadership positions in areas such as medicine, microbiology, epidemiology and global health. He is the principal investigator for the International Training & Education Center on Health (I-TECH), a collaborative program between the University of Washington and the University of California, one of the largest HIV/AIDS training programs in the world. Dr. Holmes also directs the University of Washington/Fred Hutchinson Cancer Research Center’s Center for AIDS Research. He has participated in research on STDs for over 40 years in Africa, Latin America, Southeast Asia, and the Western Pacific. He has authored over 550 peer-reviewed publications and edited 30 books, monographs, and journal supplements.

The challenge: In nature, antibodies help defend us against infectious agents such as viruses and bacteria, and for more than a century, scientists have tried to turn them against cancer. Although they succeeded in turning mouse antibodies against human cancers, when these antibodies were injected into patients to treat the cancer, they were seen as foreign and rejected by the immune system.

The work: Through his research, Sir Gregory Winter discovered how to create synthetic human antibodies against human targets (such as cancer and inflammatory disease) in a way where they will not be rejected by the immune system.

Why it matters: Sir Gregory Winter’s work in the development of antibodies for therapeutic use has led to the development of modern treatments targeted against many of the most detrimental and widespread diseases including many cancers, infectious diseases and inflammatory conditions including Herceptin, Avastin, and Humira.

Bio
Sir Gregory Winter is a member of the Medical Research Council Laboratory of Molecular Biology (LMB) in Cambridge and until recently, served as its Deputy Director. He is now the Master of Trinity College, Cambridge. Sir Gregory Winter graduated from Cambridge University in 1973, specializing in chemistry and biochemistry. He continued his studies with Cambridge University, receiving his PhD in 1976, specializing in protein and nucleic acid sequencing. Sir Gregory Winter is a pioneer in the science of protein engineering, focusing first on enzymes and then antibodies. At the LMB, he invented techniques to humanize rodent antibodies for use as therapeutics (1986), and later to make fully human antibodies (1989) using combinatorial gene repertoires. His inventions are used in about half of the antibody products on the market, including the humanized antibodies Campath-1H, Herceptin, Avastin, Synagis, and the first human antibody (Humira) to be approved by the U.S. Food and Drug Administration. Sir Winter is also an entrepreneur. He is a founder of Cambridge Antibody Technology (1989) and Domantis (2000). Both of these companies pioneered the use of antibody repertoire technologies to make fully human antibody therapeutics. In 2006, Cambridge Antibody Technology Ltd. was acquired by AstraZeneca PLC and Domantis Ltd. by GlaxoSmithKline PLC in 2006. Most recently, Sir Gregory Winter founded Bicycle Therapeutics Ltd., a biotechnology company dedicated to the development of a new generation of biotherapeutics.

The challenge: Since 1953 we have known that DNA governs the development and functioning of all known living organisms, but the area of DNA damage remained a mystery.

The work: Dr. Elledge’s research led to the identification and characterization of a signal transduction pathway, also known as the “anti-cancer pathway”, which senses and responds to DNA damage. These pathways are responsible for many things, most importantly detecting when cells have over-multiplied. When this detection occurs, the pathway sends a signal to the cell so it can begin to repair itself. This means that the pathway has the ability to suppress tumor development.

Why it matters: Dr. Elledge’s pioneering work has laid the foundation for our current understanding of DNA damage response and has informed the important field of genome instability. The discovery of signal transduction pathways lead to a new way of thinking about DNA damage. Knowledge about the inner working of this sensory pathway has led to a better understanding of how cancer occurs as well as different ways of treating it.

Bio
Dr. Stephen J. Elledge studied at the University of Illinois as an undergraduate and received his PhD in 1983 at the Massachusetts Institute of Technology (MIT) in Biology. In 1989 he was appointed Assistant Professor in the Biochemistry Department at the Baylor College of Medicine. In 1993 he became an Investigator with Howard Hughes Medical Institute and in 1995 was promoted to Professor. In 2003 he joined the Genetics Department at Harvard Medical School and the Division of Genetics at the Brigham and Women’s Hospital. Currently, Dr. Elledge is the Gregor Mendel Professor of Genetics and Medicine at Harvard Medical School. In addition to a former Helen Hay Whitney Fellow, Dr. Elledge was an American Cancer Society Senior Fellow, and a Pew Scholar. He has received many accolades and awards for his ground breaking research, including: the Michael E. Debakey Award for Research Excellence (2002), the American Association of Cancer Research G.H.A. Clowes Memorial Award (2001), the inaugural Paul Mark’s Prize in Cancer Research (2001), the National Academy of Sciences Award in Molecular Biology (2001), the John B. Carter, Jr. Technology Innovation Award (2002), an NIH Merit Award (2003), the Genetics Society of America Medal (2005), the Hans Sigrist International Prize of Bern University (2005), the Dickson Prize in Medicine (2010), the American Italian Cancer Foundation Prize for Scientific Excellence in Medicine (2012) and the Lewis Rosenstiel Award for Distinguished Work in Basic Medical Sciences (2013). In 2003 Dr. Elledge was also elected into the National Academy of Sciences and the American Academy of Arts and Sciences, to the American Academy of Microbiology in 2005, and the Institute of Medicine in 2006.

The challenge: After hepatitis A and B were discovered, a new virus emerged that could not be identified through traditional methods of viral detection. This new virus was frequently transmitted through blood transfusion, possibly leading to serious consequences such as cirrhosis (liver scarring), liver failure and even death.

The work: The combined research of these scientists led to the isolation and discovery of the hepatitis C virus and subsequent, preventative screening tests which have virtually eliminated the spread of the virus through blood-transfusions.

Why it matters: Chronic hepatitis C virus affects approximately 150 million people worldwide and can lead to liver failure, liver cancer and even death. In fact, over 350,000 people, globally, die each year from hepatitis C-related liver diseases. Diagnosis of the hepatitis C virus is now a reality and has led to treatment which can cure most patients. In hepatitis B virus and HIV infections, treatment can only control the virus, whereas in hepatitis C, treatment can eradicate the virus completely.

Bio
After graduating from San Jose State University in 1964, Dr. Bradley was recruited by the U.S. Public Health Service (USPHS) to develop methods to detect a variety of carcinogenic compounds in the atmosphere, a very dangerous task. Upon completion of his service in the USPHS, he went on to earn a Master’s degree in Biochemistry from the University of California and a Doctorate from the University of Arizona. In 1971 he was hired by the Centers for Disease Control (CDC) in Phoenix, Arizona to study whether ascorbic acid had the ability to shorten the course of respiratory virus infections. Finding no such benefit, Dr. Bradley then spent his time working on hepatitis A and B viruses, researching their infectivity in non-human primates. These studies were conducted between 1972 and 1975 and led to the identification of a new group of hepatitis viruses. In 1975, his laboratory was contacted by a scientist from Hyland Laboratories interested in the possible identification of a virus responsible for non-A, non-B hepatitis in several hemophiliac patients. Further studies conducted in 1970s and 1980s revealed the presence of a flavivirus, which led to the early identification of what is now known as hepatitis C virus (HCV). Although a fragment of the HCV genome was identified in 1987, public announcement of the successful cloning of HCV was not made until 1989.

The challenge: After hepatitis A and B were discovered, a new virus emerged that could not be identified through traditional methods of viral detection. This new virus was frequently transmitted through blood transfusion, possibly leading to serious consequences such as cirrhosis (liver scarring), liver failure and even death.

The work: The combined research of these scientists led to the isolation and discovery of the hepatitis C virus and subsequent, preventative screening tests which have virtually eliminated the spread of the virus through blood-transfusions.

Why it matters: Chronic hepatitis C virus affects approximately 150 million people worldwide and can lead to liver failure, liver cancer and even death. In fact, over 350,000 people, globally, die each year from hepatitis C-related liver diseases. Diagnosis of the hepatitis C virus is now a reality and has led to treatment which can cure most patients. In hepatitis B virus and HIV infections, treatment can only control the virus, whereas in hepatitis C, treatment can eradicate the virus completely.

Bio
Dr. Harvey Alter earned his medical degree at the University of Rochester Medical School, and trained in internal medicine at Strong Memorial Hospital and at the University of Washington Hospital in Seattle. In 1961, he came to the National Institutes of Health (NIH) as a clinical associate. He then spent several years at Georgetown University, returning to NIH in 1969 to join the Clinical Center's Department of Transfusion Medicine as a senior investigator, later becoming Chief of Clinical Studies and Associate Director of Research in the Department of Transfusion Medicine at the NIH Clinical Center. Dr. Alter co-discovered the Australia antigen, a key to detecting hepatitis B virus. Later, Dr. Alter spearheaded a project at the Clinical Center that created a storehouse of blood samples used to uncover the causes and reduce the risk of transfusion-associated hepatitis. He was principal investigator on studies that identified non-A, non-B hepatitis, now called hepatitis C. His work was instrumental in providing the scientific basis for instituting blood donor screening programs that have decreased the incidence of transfusion-transmitted hepatitis to near zero. Dr. Alter was also awarded the Clinical Lasker Award in 2000. In 2002, he became the first Clinical Center scientist elected to the National Academy of Sciences (NAS). That same year, Dr. Alter was also elected to the Institute of Medicine.

The work: Dr. Yusuf’s epidemiological work in over 60 countries in all the inhabited continents of the world shows the majority of risks of both cardiovascular and cerebrovascular disease are attributable to the same few risk factors. He currently leads the largest ever study revealing the role of societal changes in cardiovascular disease (CVD) among 155,000 people from 700 communities in 22 high, middle and low income countries. Dr. Yusuf led the HOPE Trial that demonstrated that Ramipril (an ACE inhibitor) saved lives, prevented heart attacks and strokes among patients with stable heart disease.

The impact: Dr. Yusuf’s trials (such as SOLVD, HOPE, OASIS, CHARM, ON-TARGET, TRANSCEND, etc.) on the prevention and treatment of CVD and related conditions (such as
4 hypertension and diabetes) have improved the care of patients. His research and insights have produced substantial changes in guidelines for the prevention and treatment of disease. His large trials have led to more effective treatments for acute heart attacks, congestive heart failure, heart rhythm abnormalities and chronic heart disorders. These studies have led to better understanding of the role of societal changes on behaviours and risk factors, and how they lead to CVD. Over the last three decades he has built capacity for clinical and population research across Canada and the world by establishing networks at over 1,500 sites in 85 countries.

Bio
Salim Yusuf’s work over 35 years has substantially influenced prevention and treatment of cardiovascular disease globally. Medically qualified in Bangalore 1976, he received a Rhodes Scholarship and obtained a DPhil from Oxford, during which he (along with Richard Peto and Peter Sleight) initiated the concepts of large, simple trials, and meta-analysis. He coordinated the ISIS trial (which set the structure for future international collaborative work in cardiovascular disease) that demonstrated the value of beta-blockers in myocardial infarction, and sat on steering committees for all subsequent ISIS trials.

In 1984, he moved to the National Institutes of Health, Bethesda, USA, where he was a leader in their SOLVD trial (establishing the value of ACE-inhibitors on LV dysfunction) and DIG trial (clarifying the role of digitalis). In 1992 he moved to McMaster University, where he has established an international program of research in cardiovascular diseases and prevention, culminating in the creation of the Population Health Research Institute, which he founded and heads. His therapeutic trials have established the roles of ACE-inhibitors in CVD prevention (the HOPE study), dual antiplatelet therapies in acute coronary syndromes (the CURE study), and the roles of novel antithrombotics and invasive interventions. The PHRI was recently cited by SCImago as possessing the highest impact of Canadian Centers and the 7th highest impact in the world.

His epidemiologic work in over 60 countries in all the inhabited continents of the world shows the majority of risks of both cardiovascular and cerebrovascular disease are attributable to the same few risk factors. He currently leads the largest ever study revealing the role of societal changes in CVD among 155,000 people from 700 communities in 22 high, middle and low income countries. These studies have led to better understanding of the role of societal changes on behaviours and risk factors, and how they lead to CVD.

Over the last 3 decades he has built capacity for clinical and population research across Canada (first through the Canadian Cardiovascular Collaboration, and more recently through CANNeCTIN) and the world by establishing networks at over 1500 sites in 85 countries, spanning all inhabited continents of the world. He has trained over 50 researchers, many of whom are nationally or internationally renowned leaders in medical research. He has helped develop major research institutes or programs in Canada, India, Argentina, Brazil, S. Africa, Saudi Arabia, Malaysia, and China.

He holds a Heart and Stroke Foundation of Ontario Research Chair, was a Senior Scientist of the Canadian Institutes of Health Research (1999-2004), and has received over 35 international and national awards for research, induction into the Royal Society of Canada, an appointment as an Officer of the Order of Canada, and in 2014 he will be inducted into the Canadian Medical Hall of Fame.

He has published over 800 articles in refereed journals, rising to the second most cited researcher in the world for 2011. He is President-elect of the World Heart Federation, where he is initiating an Emerging Leaders program in 100 countries with the aim of halving the CVD burden globally within a generation.

The work: In 1973, the Kitasato Institute in Japan, led by Professor Satoshi Omura, formed a collaborative research partnership with Merck to discover new animal health products. Within this partnership, Professor Omura and his research team based at the Kitasato Institute in Tokyo isolated and screened microorganisms and sent the promising ones to the Merck laboratories in the United States. Of particular interest was a microorganism, Streptomyces avermitilis, isolated from soil near an oceanside golf course in Japan which had potent bioactivity. Researchers at Merck’s lab conducted further testing on the microorganism and then the compound responsible for the activity was named avermectin. Scientists at Merck refined avermectin under the name ivermectin, which was the safest and most potent derivative. Despite decades of searching around the world, the Japanese microorganism remains the only source of avermectin ever found.

The impact: Ivermectin, commercialized in 1981 as a highly successful veterinary drug active against both internal and external parasites, was later found to be safe and effective for treating several human parasitic diseases such as Onchocerciasis (river blindness) and Lymphatic filariasis (elephantiasis). Merck joined forces with the World Health Organization (WHO), the Special Programme for Research and Training in Tropical Diseases (TDR) and the Onchocerciasis Control Programme in West Africa (OCP) to test the drug in humans. Ivermectin was registered for human use by French regulators in 1987. With the Kitasato Institute agreeing to forego royalties, Dr. Roy Vagelos, the then Chief Executive of Merck, announced that ivermectin would be provided free of charge for the treatment of river blindness for “as long as it is needed,” a pledge that is still being honoured. Utilizing a truly international partnership involving the public and private sectors, governments of disease-endemic countries and affected communities, mass drug administration commenced in 1988 and the donation has allowed the goal of eliminating both diseases to become achievable in the near future. Ivermectin has also become the drug of choice to treat strongyloidiasis, scabies and head lice and research is being conducted into its effectiveness against other neglected tropical diseases.

Bio
Prof. Satoshi Ōmura received an M.S. degree in 1963 from Tokyo University of Science, followed by a Ph.D. in Pharmaceutical Sciences in 1968 from the University of Tokyo, and another in Chemistry two years later from the Tokyo University of Science. His first position was as a Research Associate at University of Yamanashi (1963-1965). In 1965 he began his career-long association with the Kitasato Institute, initially as a researcher, over the years occupying various posts, culminating in his appointment in 1990 as President. He served as President Emeritus of The Kitasato Institute (2008-2012), and is currently a Distinguished Emeritus Professor and Special Coordinator of the Research Project for Drug Discovery from Natural Products in the Kitasato Institute for Life Sciences, Kitasato University. He was also appointed as inaugural Max Tishler Professor of Chemistry at Wesleyan University (USA) in 2005.

Commencing with his studies in Organic Chemistry at the Tokyo University of Science, from 1965 onwards he has performed comprehensive research on Bioorganic Chemistry, focusing on bioactive substances of microbial origin. He devised several innovative new methods for isolating and culturing microorganisms and established many original methods of screening for bioactive substances. As a result, he has discovered more than 470 novel bioactive compounds. Among them, the globally significant anthelmintic antibiotic avermectin and its derivatives, seen by many to rival penicillin in their impact on global health, were discovered through collaborative research with Merck Sharp & Dohme Research Laboratories (USA), his group eventually deciphering the entire genome of the producing organism, Streptomyces avermectinius.

Prof. Ōmura has been widely recognized in the natural-products chemistry field, as evidenced by his numerous awards and honors. Among these are the Hoechst-Roussel Award from American Society for Microbiology, Charles Thom Award (Society for Industrial Microbiology, USA), Robert Koch Gold Medal (Germany), Prince Mahidol Award (Thailand), Nakanishi Prize of Japan Chemical Society and the American Chemical Society, Ernest Gunther Award of the American Chemical Society, Hamao Umezawa Memorial Award of the International Society of Chemotherapy, Tetrahedron Prize for Creativity in Organic Chemistry, Arima Award of the International Union of Microbiology, and the Japan Academy Prize. He has been decorated with France’s L’Ordre National de la Legion d’Honneur Chevalier in 2007, and also has been designated by Japan in 2012 as a highly-prestigious Person of Cultural Merit.

The work: The problem de Lange has focused on for the past two decades is a basic problem in cell biology. Chromosomes are made of protein and a single molecule of deoxyribonucleic acid (DNA) and have two ends. Our body has a vigilant surveillance system which is always looking for damage to our DNA, including breaks which can lead to various diseases, such as cancer. The ends of chromosomes are called telomeres and Dr. de Lange discovered that they are bound by a complex of proteins she named shelterin. De Lange’s work addressed the mechanism by which telomeres protect chromosome ends, an issue she refers to as the “telomere end-protection problem.” De Lange revealed that telomeres need to repress six distinct DNA damage response (DDR) pathways that threaten genome integrity. She identified the shelterin protein complex that protects telomeres and established how distinct shelterin subunits repress different DDR pathways.

The impact: Her work has solved a long-standing riddle in biology, one that has profound implications for our understanding of effective cell proliferation, chromosome integrity and a diverse array of human disorders including cancer and aging. The work on the telomere end- protection problem and the types of genome instability that result from lack of telomere function has informed scientists about the events involved in early tumorigenesis when telomeres shorten due to the lack of telomerase. De Lange’s findings argue that the genome instability in human cancer is in part due to loss of telomere function. Furthermore, understanding how telomeres solve the end-protection problem is directly relevant to the telomeropathies, which are diseases caused by compromised telomere function.

Bio
Titia de Lange received training in biochemistry at the University of Amsterdam and the Dutch Cancer Institute. As part of her undergraduate training, she worked on globin gene expression with Richard Flavell at the NIMR in Mill Hill before joining Piet Borst in 1981 at the Dutch Cancer Institute as a graduate student. In 1985, she obtained her PhD (cum laude) and joined Harold Varmus at UCSF for postdoctoral studies. With Varmus, she isolated human telomeric DNA and was the first to show that tumor telomeres shorten. In 1990, she was appointed as Assistant Professor at the Rockefeller University where she was promoted to Professor in 1997. She currently is the Leon Hess Professor, an American Cancer Society Research Professor, and the Director of the Anderson Cancer Center at the Rockefeller University. De Lange is a (foreign) member of EMBO, the US National Academy of Science, the Dutch Royal Academy of Sciences, the American Academy of Arts and Science, the American Association for Advancement of Science, the American Society for Microbiology, the New York Academy of Science, and the Institute of Medicine. De Lange was awarded the inaugural Paul Marks Prize for Cancer Research, the Massachusetts General Hospital Cancer Center Prize, the AACR’s Charlotte Friend and G.H.A. Clowes Awards, the Vilcek Prize, the Vanderbilt Prize, the Dr. H.P. Heineken Prize, and the Breakthrough Prize in Life Sciences. She holds an honorary degree from the University of Utrecht. De Lange has served on the scientific advisory boards of many US and European academic institutions, including MSKCC, CSHL, the MIT Cancer Center, the IMP in Vienna, the CRUK/LRI in London, and the Ludwig Institute for Cancer Research. De Lange also serves on several award committees, including the Lasker Jury, the Vilcek Prize selection committee, and the Pearl Meister Greengard Prize committee.

The work: Allison’s research has focused on T cell biology. T cells are white blood cells that scan our bodies for cellular abnormalities and infections. Allison’s work discovered the receptor these cells use to recognize and bind to antigens for attack. Immunologists have long wondered why the immune system doesn’t fight off cancer cells itself and Allison discovered the first ‘blocker’ that blocks the immune system from doing so. This discovery was the immune checkpoint molecule called CTLA-4, which turns off T cells before they can respond to tumors they’ve been set to destroy. Allison developed an antibody to block CTLA-4, freeing T cells to attack tumors, and leading to the development of the drug ipilimumab. The U.S. Food and Drug Administration (FDA) approved ipilimumab (Yervoy®) for treatment of metastatic melanoma in 2011.

The impact: Allison’s concept has opened a new field of cancer therapy, immune checkpoint blockade, and many cancer patients are alive today because of his vision. Immune checkpoint blockade treats the immune system instead of the tumor which provides the option to work across other cancers. In addition to melanoma, ipilimumab has been effective in clinical trials against prostate, kidney, lung and ovarian cancers.

Bio
Dr. Allison is a professor and chair of the Department of Immunology, executive director of the Immunotherapy Platform and deputy director of the David H. Koch Center for Applied Research of Genitourinary Cancers at The University of Texas MD Anderson Cancer Center. A recent addition to MD Anderson in November 2012, Dr. Allison is building a team of clinicians and physician-scientists to accelerate the movement of immune-based combinatorial therapies into clinical trials. Since joining us, he has already received funding from Stand Up to Cancer and the Cancer Research Institute (SU2C/CRI) to lead a Dream Team in Translational Immunology Research with the aim of facilitating clinical development of new and improved forms of cancer immunotherapy.

Dr. Allison received a B.S. in microbiology and a Ph.D. in biological sciences from the University of Texas at Austin, then completed a postdoctoral fellowship in the Department of Molecular Immunology at the Scripps Clinic and Research Foundation in California. He began his academic career as an assistant professor in the Department of Biochemistry at the University of Texas, Science Park–Research Division in Smithville, Texas, and quickly achieved the rank of professor in the Department of Molecular and Cellular Biology, Division of Immunology at the University of California, Berkeley. Dr. Allison was recruited to MD Anderson from Memorial Sloan-Kettering Cancer Center, where he had been the chair of the Immunology Program, the attending immunologist and director of the Ludwig Center for Cancer Immunotherapy, and a professor at the Weill Medical College of Cornell University since 2004.

Dr. Allison has more than 260 publications, including articles in Nature, Science, Cell, Immunity, Cancer Cell and Blood. He has received numerous awards in recognition of his seminal work, including the Dana Foundation Award in Human Immunology Research (2008), the Richard V. Smalley, M.D. Memorial Lectureship Award (2010), a Lifetime Achievement Award from the American Association of Immunologists (2011), the Roche Award for Cancer Immunology and Immunotherapy (2011), the Novartis Prize for Clinical Immunology (2013), and the Breakthrough Prize in Life Sciences (2013).

The work: Rheumatoid arthritis (RA) is a common, chronic, painful and disabling autoimmune disease. Prior to the work of Drs. Feldmann and Maini, the treatment of RA was not based on understanding of which molecules were produced in excess. In the mid-1980’s, the team began work on unravelling which molecules might be the culprit of this disease in hopes of determining which targets would be ideal for treatment. Experiments in the laboratory on cells from joints of patients and in an animal model of RA demonstrated that tumor necrosis factor (TNF), a molecule belonging to the ‘cytokine’ family, was a major driver of inflammation and joint damage. They discovered a monoclonal antibody-based treatment that blocked the action of TNF and was safe and effective for treating in RA. Anti-TNF therapy works in most patients rapidly to reduce pain, improve mobility, reduce work disability, improve social functioning, and, when compared with patients on conventional synthetic drug treatments, reduces the risk of heart attacks, strokes and increases life expectancy. It has a major role in protecting joints from degeneration, thus maintaining good physical function and reducing the need for joint surgery.

The impact: They discovered the first treatment for RA, using monoclonal antibodies which are genetically engineered natural defense molecules. Not only was this a novel treatment, but it was the first demonstration of the efficacy of a biological therapy for a chronic autoimmune disease and led to the recognition by the pharmaceutical industry that biological drugs are a viable class of therapeutic agents that can compete with traditional chemical drugs. The effective results have not only transformed the treatment for patients, but have led to other successful anti-TNF treatments, and encouraged much further work using antibodies for treatment.

Bio
Sir Ravinder Maini, born to Indian parents, received his early school education in Uganda and has resided permanently in the UK since 1955. After high school in London, he studied medicine at Cambridge University and Guy's Hospital; London (qualified BA MB BChir 1962). He undertook his postgraduate clinical training and a Fellowship in clinical immunology. Throughout his professional career since 1970 he has combined practice as a Clinician-Scientist in rheumatology and internal medicine with laboratory-based immunological research. From 1990 to 2002 he was Professor and Scientific Director/Head of The Kennedy Institute of Rheumatology, London.

His research has focussed on immunological and inflammatory mechanisms and therapy of autoimmune rheumatic diseases. His ‘bench to bedside’ research, in collaboration with Marc Feldmann which commenced in 1985, resulted in the development of anti-TNF immunotherapy of rheumatoid arthritis. He has been invited as a keynote speaker at International scientific meetings; published over 480 papers in scientific journals; served on the Editorial Board of immunology and rheumatology journals; and is currently Co-Editor in Chief of the open access journal 'Arthritis Research and Therapy'.

Since retirement, he is a Visiting Professor to the Kennedy Institute of Rheumatology at Oxford. He continues to serve as a Consultant and Advisor to the Biotechnology and Pharmaceutical industry and National Grant-Giving Agencies. He serves as a Trustee of Medical Charities, currently a Trustee and President of the Kennedy Trust for Rheumatology Research, UK, and Trustee of The Sir Jules Thorn Trust.

His research contributions have been recognised the awards of a Knighthood (2003) by HM Queen Elizabeth; election to learned scientific societies: he is a Fellow of Royal Society, London (FRS), Fellow of the Academy of Medical Sciences (FMedSci), Foreign Associate Member of the USA Academy of Sciences, Fellow of the Royal Colleges of London and Edinburgh and Honorary Fellow of Sidney Sussex College, Cambridge; honorary Doctorates of the Universities of Glasgow and University Rene Descartes, Paris; Distinguished Investigator Award by the American College of Rheumatology; and Honorary Fellowships of Scientific Societies in the United Kingdom, Europe and Australia.

Following the identification of TNF as a therapeutic target and translation of anti-TNF therapy to the clinic, Professors Maini and Feldmann have been jointly awarded many prizes, notably the Crafoord Prize by The Royal Swedish Academy of Sciences, The Lasker prize for Clinical Research, Dr Paul Jannsen Award for Biomedical Research, Ernst Schering Prize and in 2014, they have been selected as recipients of the Canada Gairdner International Award.

The work: Rheumatoid arthritis (RA) is a common, chronic, painful and disabling autoimmune disease. Prior to the work of Drs. Feldmann and Maini, the treatment of RA was not based on understanding of which molecules were produced in excess. In the mid-1980’s, the team began work on unravelling which molecules might be the culprit of this disease in hopes of determining which targets would be ideal for treatment. Experiments in the laboratory on cells from joints of patients and in an animal model of RA demonstrated that tumor necrosis factor (TNF), a molecule belonging to the ‘cytokine’ family, was a major driver of inflammation and joint damage. They discovered a monoclonal antibody-based treatment that blocked the action of TNF and was safe and effective for treating in RA. Anti-TNF therapy works in most patients rapidly to reduce pain, improve mobility, reduce work disability, improve social functioning, and, when compared with patients on conventional synthetic drug treatments, reduces the risk of heart attacks, strokes and increases life expectancy. It has a major role in protecting joints from degeneration, thus maintaining good physical function and reducing the need for joint surgery.

The impact: They discovered the first treatment for RA, using monoclonal antibodies which are genetically engineered natural defense molecules. Not only was this a novel treatment, but it was the first demonstration of the efficacy of a biological therapy for a chronic autoimmune disease and led to the recognition by the pharmaceutical industry that biological drugs are a viable class of therapeutic agents that can compete with traditional chemical drugs. The effective results have not only transformed the treatment for patients, but have led to other successful anti-TNF treatments, and encouraged much further work using antibodies for treatment.

Bio
After training in medicine and realising that research was the path towards improving therapy, he studied for a PhD in immunology at the Walter and Eliza Hall Institute in Melbourne with Prof. Sir Gus Nossal. There he learnt to optimise immune responses in tissue culture, and also studied potent intercellular mediators, molecules later identified as cytokines, autoimmunity and immuneregulation.

In 1983, while working in Av Mitchison’s ICRF Tumour Immunology Unit at University College London, on reflecting about the new observations of upregulated MHC class II in local sites of autoimmunity (e.g. thyroid) he proposed that this reflected augmented antigen presentation. Since cytokines, especially interferons upregulate MHC antigens, in 1983 he published a hypothesis that upregulated cytokines and antigen presentation were key steps in the generation of a chronic autoimmune disease. This was a testable hypothesis, and was successfully tested on Grave’s thyroiditis by 1985-6. This led to collaboration with Ravinder Maini, relocation to the Kennedy Institute, and the exploration of what were critical cytokines in the most accessible human autoimmune disease, rheumatoid arthritis. New methods were developed to assess which cytokines were produced locally demonstrating that many pro-inflammatory cytokines were produced. To unravel which was the best target, he analysed cytokine regulation in dissociated rheumatoid arthritis synovial tissue, and found that blockade of TNF also downregulated IL-1 and other pro-inflammatory cytokines, indicating that TNF was the long sought after therapeutic target. This was validated in mouse arthritis, treatment given after disease onset. Thus there was a rationale for a proof-of-principle clinical trial of anti-TNF, and he was a leader with my colleague Prof. Sir Ravinder Maini of this and subsequent clinical trials which led to approval for anti-TNF therapy in rheumatoid arthritis. This success and that of other anti-TNF antibodies has made anti-TNF the best-selling drug class from 2012. He succeeded Ravinder Maini as Director of Kennedy Institute in 2002.

This work has led to his election to various national academies of science (e.g. Royal Society, Australian Academy of Science and the National Academy of Science, USA), and multiple prestigious prizes, mostly with his colleague Sir Ravinder Maini, e.g. Crafoord Prize of Royal Swedish Academy, the Albert Lasker Clinical Medical Research Award, Ernst Schering Prize, Paul Janssen prize.

The work: Blood vessels are the part of the circulatory system that transports blood throughout the body and also play a vital role in virtually every medical condition. In 1983, Dr. Dvorak reported a tumour-derived protein that caused the cells lining tumor blood vessels to become leaky (hyperpermeable) to circulating molecules. He called the protein vascular permeability factor (VPF). Subsequently, he demonstrated that VPF was also secreted by many normal cells and plays a key role in wound healing and chronic inflammatory diseases. At the same time, Dr. Ferrara noted that cells released a factor that caused cells to divide. This factor stimulated the production of new blood vessels from pre-existing vessels (angiogenesis). In 1989, Dr. Ferrara reported for the first time the isolation and sequencing of vascular endothelial growth factor (VEGF) which, after testing, ended up being the exact same molecule as VPF, and VEGF became its new name.

The impact: Dr. Dvorak’s research demonstrated that most malignant tumors make VEGF, which assists the tumors to grow beyond minimal size by forming new blood vessels and connective tissue support as in wound healing. Dr. Ferrara’s cloning and characterization of VEGF enabled progress in this field. In addition, Dr. Ferrara and his team made key advances in understanding how VEGF was made, how it acted and its role. Importantly, Dr. Ferrara and his colleagues pioneered the clinical development of an inhibiting antibody against VEGF which opened up a new era of cancer therapy because this new approach focused on choking off the blood supply that tumours need in order to grow and spread. These findings also spearheaded the development of an anti-VEGF antibody fragment (ranibizumab) which has shown dramatic efficacy in maintaining and improving vision in wet age-related macular degeneration (AMD) patients.

Bio
Dr. Ferrara earned his M.D. degree in 1981 from the University of Catania Medical School in Italy. After completing his postdoctoral research at the University of California, San Francisco, he joined Genentech Inc. in 1988. It is there where he spent nearly 25 years working on the molecular characterization and therapeutic applications of VEGF-A, which resulted in the development of bevacizumab, the first anti-angiogenic agent to be approved by the FDA for cancer therapy. His research also led to the development of ranibizumab, which has been FDA-approved for the treatment of multiple intraocular neovascular disorders. In January 2013, Dr. Ferrara joined the University of California, San Diego as a Distinguished Professor of Pathology, Distinguished Adjunct Professor of Ophthalmology and Senior Deputy Director for Basic Sciences of the Moores Cancer Center.

Dr. Ferrara has authored over 300 scientific publications. He is also the recipient of numerous awards including the Lefoulon-Delalande-Institut-de-France Prize, the Passano Award, the General Motors Cancer Research Award, the ASCO Science of Oncology Award, the Pezcoller Foundation-AACR International Award, the Lasker-deBakey Clinical Medical Research Award, the Dr. Paul Janssen Award, the Economist Innovation Award and the inaugural Breakthrough Prize in Life Sciences. Dr. Ferrara has been a member of the National Academy of Sciences, USA, since 2006.

The work: Blood vessels are the part of the circulatory system that transports blood throughout the body and also play a vital role in virtually every medical condition. In 1983, Dr. Dvorak reported a tumour-derived protein that caused the cells lining tumor blood vessels to become leaky (hyperpermeable) to circulating molecules. He called the protein vascular permeability factor (VPF). Subsequently, he demonstrated that VPF was also secreted by many normal cells and plays a key role in wound healing and chronic inflammatory diseases. At the same time, Dr. Ferrara noted that cells released a factor that caused cells to divide. This factor stimulated the production of new blood vessels from pre-existing vessels (angiogenesis). In 1989, Dr. Ferrara reported for the first time the isolation and sequencing of vascular endothelial growth factor (VEGF) which, after testing, ended up being the exact same molecule as VPF, and VEGF became its new name.

The impact: Dr. Dvorak’s research demonstrated that most malignant tumors make VEGF, which assists the tumors to grow beyond minimal size by forming new blood vessels and connective tissue support as in wound healing. Dr. Ferrara’s cloning and characterization of VEGF enabled progress in this field. In addition, Dr. Ferrara and his team made key advances in understanding how VEGF was made, how it acted and its role. Importantly, Dr. Ferrara and his colleagues pioneered the clinical development of an inhibiting antibody against VEGF which opened up a new era of cancer therapy because this new approach focused on choking off the blood supply that tumours need in order to grow and spread. These findings also spearheaded the development of an anti-VEGF antibody fragment (ranibizumab) which has shown dramatic efficacy in maintaining and improving vision in wet age-related macular degeneration (AMD) patients.

Bio
Dr. Harold F. Dvorak is the founding Director of the Center for Vascular Biology Research (CVBR) at the Beth Israel Deaconess Medical Center (BIDMC) and the Mallinckrodt Distinguished Professor of Pathology at Harvard Medical School. In 1983, Dr. Dvorak and his colleagues were the first to demonstrate that tumor cells secreted vascular endothelial growth factor (VEGF), known at the time as vascular permeability factor or VPF. This seminal discovery provided the molecular basis for the field of angiogenesis. Dr. Dvorak went on to make the critically important observation that tumors behave like “wounds that do not heal” in that the vascular and stromal responses they induce closely mimic those of healing wounds. More recently, his work has characterized the different types of blood vessels that tumors generate and the molecular mechanisms by which they form.

Dr. Dvorak has taught for many years at the Harvard Medical School, and has lectured frequently as a visiting professor and at numerous national and international scientific conferences. He is a fellow of the American Association for the Advancement of Science and of the National Foundation for Cancer Research and has served as President of the American Society for Investigative Pathology which awarded him the 2002 Rous-Whipple award, and, forthcoming in 2013, the Gold-headed cane award for his scientific accomplishments. In 2005 he received the Grand Prix Lefoulon-Delalande from the Institut de France and in 2006 the inaugural Albert Szent-Gyorgyi Prize for Progress in Cancer Research from the National Foundation for Cancer Research (NFCR). Educated at Princeton University and Harvard Medical School, he did a Pathology residency at the Massachusetts General Hospital and postdoctoral research at the National Institutes of Health. He has served on the Harvard Medical School faculty since 1967 and at BIDMC since 1979. After stepping down after 26 years as Chair of Pathology at BIDMC in July 2005, Dr. Dvorak focused his efforts on building the CVBR, while at the same time continuing to pursue his research.

The work: To stay healthy our immune system needs to discriminate between itself and invaders (non-self). When unable to differentiate between the two, the immune system destroys healthy cells or tissues causing autoimmune diseases. Dr. Sakaguchi discovered regulatory T (Treg) cells which help maintain order in the immune system and act as a ‘self-check’ to prevent excessive reactions as without Treg cells the body would attack the healthy cells and die. He was the first to determine their molecular basis and function.

The impact: Within his laboratory, Dr. Sakaguchi demonstrated that increasing the number of Treg cells can prevent and treat autoimmune diseases. Further, Treg cells suppress the immune system against cancer and there are now several clinical trials within this area.

Bio
Shimon Sakaguchi is a Distinguished Professor at the World Premier International Research Initiative (WPI)-Immunology Frontier Research Center (IFReC) at Osaka University, Japan. He is an immunologist recognized for his work on the control of immune responses. He is known particularly for his discovery of regulatory T cells, an indispensable constituent of the immune system for the maintenance of immune self-tolerance and homeostasis. Sakaguchi was born in Japan in 1951, obtained an M.D. in 1976 and a Ph.D. in 1982 from Kyoto University, Japan, where he was trained as a pathologist and immunologist. After performing postdoctoral studies at Johns Hopkins University and Stanford University as a Lucille P. Markey Scholar, he served as an Assistant Professor in the Department of Immunology at the Scripps Research Institute. He returned to Japan in 1991 and continued his immunology research at RIKEN Institute as an Investigator of the Japan Science and Technology Agency and subsequently as the Head of the Department of Immunopathology at Tokyo Metropolitan Institute of Gerontology, Tokyo. From 1998 to2011, he was a Professor and the Chairman of the Department of Experimental Pathology, Institute for Frontier Medical Sciences Kyoto University and served as the Director of the Institute for several years. In 2011, his lab moved to Osaka University and he assumed the current position as University Distinguished Professor of Osaka University.

The work: Dr. Rossant is a world leader in developmental and stem cell biology. Dr. Rossant has provided significant insights into how an embryo develops, how genes control development and how pluripotent and other stem cells are established. Her research interests focus on understanding the genetic control of normal and abnormal development in the mouse embryo and its impact on human development and disease.

The impact: By understanding the underpinning of early development in the mouse embryo, she has contributed to the understanding of human embryo development and stem cell origins. Her interests in the early embryo led to the discovery in 1998 of a novel placental stem cell type, the trophoblast stem cell. This work has highlighted how congenital anomalies in the heart, blood vessels and placenta can arise. Further, her research on the genes controlling blood vessel development has defined novel pathways for new drug interventions in cancer. Throughout her career, Dr. Rossant has been a pioneer and innovator of new techniques to manipulate the mouse genome, enabling the mouse to become the pre-eminent model for understanding the function of the human genome sequence.

Bio
Dr. Janet Rossant, SickKids Chief of Research and a world-renowned expert in developmental biology, is the definition of a trailblazer. Widely known for her studies of the genes that control embryonic development in the mouse, Rossant has pioneered techniques for following cell fate and altering genes in embryos. This work continues to resonate in medical genetic research. Her current research focuses on stem cell development and cell differentiation in the developing embryo, important areas for the study of birth defects as well as regenerative medicine. Firmly planted on the front lines of technological change, Rossant has established SickKids as a global forerunner in genetic research.

Dr. Rossant trained at the Universities of Oxford and Cambridge, United Kingdom and has been in Canada since 1977, first at Brock University and then at the Samuel Lunenfeld Research Institute within Mount Sinai Hospital in Toronto, from 1985 to 2005. She joined SickKids in 2005. Dr. Rossant has been recognized for her contributions to science with many awards, including the Ross G. Harrison Medal (lifetime achievement award) from the International Society of Developmental Biologists, the Killam Prize for Health Sciences, the March of Dimes Prize in Developmental Biology, the Conklin Medal from the Society for Developmental Biology, and the CIHR Michael Smith Prize in Health Research. She is a Fellow of both the Royal Societies of London and Canada, and is a foreign Associate of the US National Academy of Science. Rossant was most recently recognized in October 2014 with the 10th ISTT Prize, from the International Society for Transgenic Technologies in Edinburgh, Scotland.

The work: Dr. Piot is a co-discoverer of the Ebola virus and its modes of transmission and its epidemiology. His pioneering work on HIV/AIDS in Africa revealed a major heterosexual HIV epidemic, established much of the knowledge of the clinical manifestations, natural history and epidemiology of HIV in Africa, including the first studies showing the effectiveness of HIV prevention in high risk populations. He also identified several original risk determinants for HIV transmission. His team was the first to document the association between tuberculosis (TB) and HIV in Africa, and the wide genetic diversity of HIV-1 in Africa, as well as a related immunodeficiency virus in chimpanzees.

The impact: Dr. Piot played a leading role in bringing the AIDS epidemic to the forefront of global attention, raising international commitments to its funding and building scientifically grounded responses to its control and treatment. His team’s work on the strong association of tuberculosis and HIV in Africa, followed by clinical and therapeutic studies, led to new guidelines for managing tuberculosis in Africa. His studies on the prevention of HIV infection among high risk populations were again among the first in Africa, and demonstrated that such prevention is possible.

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Peter Piot MD PhD FRCP FMedSci is the Director of the London School of Hygiene & Tropical Medicine School, and Professor of Global Health. He was the founding Executive Director of UNAIDS and Under Secretary-General of the United Nations from 1995 until 2008, and was an Associate Director of the Global Programme on AIDS of WHO. A clinician and microbiologist by training, he co-discovered the Ebola virus in Zaire in 1976, and subsequently led research on AIDS, women’s health, and sexually transmitted infections, mostly in Africa. He has held academic positions at the Institute of Tropical Medicine, Antwerp, , the University of Nairobi, the University of Washington, Imperial College London, and was a Senior Fellow at the Bill and Melinda Gates Foundation. He held the chair 2009/2010 “Knowledge against poverty” at the College de France in Paris.

He is a member of the Institute of Medicine of the US National Academy of Sciences, and of the Royal Academy of Medicine of his native Belgium, and a fellow of the Academy of Medical Sciences and the Royal College of Physicians. He was the President of the International AIDS Society, and of the King Baudouin Foundation. In 1995 he was ennobled as a Baron by King Albert II of Belgium.. He has received numerous awards for his research and service, including the Nelson Mandela Award for Health and Human Rights , the F.Calderone Medal , the Hideyo Noguchi Africa Prize , the Prince Mahidol Award for Public Health , and the 2015 Canada Gairdner Global Health Award . He has published over 570 scientific articles and 16 books, including his memoir “No time to lose”.

The work: He was the first person to visually observe the function of autophagy (self-eating), whereby cells clean up the garbage within them by killing invaders and keeping healthy cells. It works as a cell recycling system to maintain homeostasis within the body. He then clarified the mechanism of autophagy and the genes involved.

The impact: Autophagy is now regarded as a vital cell-recycling system and may aid in future developments to treat neurodegenerative diseases such as Alzheimer’s, cancer and other age- related diseases. Dr. Ohsumi’s research findings have since been applied to autophagy in animals as well, and many researchers are now working to further clarify the molecular mechanism and physiological significance of this process.

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Dr. Yoshinori Ohsumi was born in Fukuoka in 1945. In 1963, he entered to The Univ. of Tokyo, then he chose decisively to follow molecular biology as the path of his future. As a graduate student, Dr. Ohsumi studied the initiation mechanism of E. coli ribosome and then action of colicin E3, which inhibits the translation of E. coli cells by binding to its receptor. Near the end of 1974, he enrolled in Rockefeller Univ., to study under Dr. G. M. Edelman. First Dr. Ohsumi worked on in vitro fertilization in mice, then switched to work on the mechanism of initiation of DNA replication using yeast, which introduced him to yeast research. Dr. Ohsumi returned to Japan at the end of 1977, and worked as an assistant professor under Prof. Y. Anraku, at the Faculty of Science, The Univ. of Tokyo. Dr. Ohsumi decided to take up the study of the yeast vacuolar membrane. By making pure vacuolar membrane vesicles, he succeeded to show various active transport systems and a novel type of proton-pump, v-type ATPase on the vacuolar membrane. In 1988, Dr. Ohsumi became an associate professor in College of Arts and Sciences of The Univ. of Tokyo and opened up his own small lab. He decided to work on the lytic function of the vacuole. Soon after, Dr. Ohsumi found yeast autophagy by light and electron microscopy. Taking advantage of yeast system, he performed a genetic screen for autophagy-defective mutants. His group could get 15 genes essential for starvation-induced autophagy by the first screen, and started cloning of these ATG genes. Then Dr. Ohsumi moved to The National Inst. for Basic Biology at Okazaki, and uncovered that these Atg proteins consist of six unique functional groups, such as a protein kinase complex, two ubiquitin-like conjugation systems, a PtdIns 3-kinase complex and so on. Drs. T. Yoshimori and N. Mizushima in his lab started studies on ATG genes in mammals and a student also worked on plant, proving that the ATG system is well conserved in higher eukaryotes. However, up to now, Dr. Ohsumi has focused on dissection of the molecular mechanism of the Atg proteins in yeast. In 2009, Dr. Ohsumi moved to Tokyo Inst. of Technology, and continues to elucidate the molecular details of membrane dynamics during autophagosome formation and the physiological relevance of autophagy by combination of cell biology, biochemistry, molecular biology, and structural biology.

The work: Messenger RNA (mRNA) takes genetic instructions from DNA and uses them to create proteins that carry out multiple cellular functions. Dr. Maquat discovered nonsense- mediated mRNA decay (NMD) in human cells. NMD is a quality control mechanism that removes flawed messenger RNA molecules that, if left intact, would lead to the production of abnormal proteins that could be toxic to cells and initiate disease. Cells also use this pathway to better respond to changing environmental conditions. For example, breast cancer cells inhibit this pathway to augment their response to chemotherapy and hasten cell death.

The impact: Nonsense-mediated mRNA decay functions in one-third of inherited disorders, such as cystic fibrosis, and one-third of acquired diseases, including many forms of cancer. Her work has furthered our understanding of the molecular basis of human disease and provides valuable information to help physicians implement “personalized” or “precision” medicine by treating the disease mutation that is specific to each individual patient.

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Lynne E. Maquat holds the J. Lowell Orbison Endowed Chair and is Professor of Biochemistry & Biophysics and Professor of Oncology in the School of Medicine and Dentistry, Director of the Center for RNA Biology: From Genome to Therapeutics, and Chair of Graduate Women in Science at the University of Rochester in Rochester, New York, USA. After obtaining her PhD from the University of Wisconsin-Madison and post-doctoral work at the McArdle Laboratory for Cancer Research in Madison, she joined the Roswell Park Cancer Institute in Buffalo before moving her laboratory to the University of Rochester. Professor Maquat is known for her mammalian-cells studies of nonsense-mediated messenger RNA decay, which she first reported in 1981 through studies of the hemolytic anemia bo-thalassemia and from which she subsequently discovered the pioneer round of translation, the exon-junction complex (EJC), and how the EJC marks mRNAs for a first quality-control translation cycle that largely occurs as newly synthesized messenger RNAs enter the cytoplasm. She continues to make seminal contributions on mechanisms of NMD and another pathway she discovered and named Staufen-mediated mRNA decay (SMD). Her work on SMD has defined new roles for long non-coding RNAs and small interspersed elements in humans and rodents, unveiling the complexities of RNA-RNA interactions that comprise important post-transcriptional gene regulatory pathways during mammalian-cell development and differentiation. Professor Maquat has served on editorial boards including RNA, Mol. Cell Biol., RNA Biol., and Methods, as an elected Director, Treasurer/Secretary and President of the RNA Society, as a member of the Public Information Committee of the American Society for Cell Biology, and as chair of NIH study section. She is an elected Fellow of the American Association for the Advancement of Science (2006), an elected Member of the American Academy of Arts and Sciences (2006) and the National Academy of Sciences (2011), and a Batsheva de Rothschild Fellow of the Israel Academy of Sciences and Humanities (2012). Professor Maquat was awarded the William C. Rose Award from the American Society for Biochemistry and Molecular Biology (2014) for research and mentoring, in particular advocacy for women in science.

The work: Cell division, growth and death are the most fundamental features of life. Dr. Hall discovered and named the protein “target of rapamycin” (TOR), which regulates cell growth. In TOR, Hall found a key protein in cellular communication that when blocked pharmacologically can contain the uncontrolled cell growth and division that is typical for cancer. TOR is also a central controller of cell growth that plays a key role in development and TOR was the first protein that demonstrated to influence longevity in all of the four ageing species that scientists commonly use to study ageing: yeast, worms, flies and mice.

The impact: Dr. Hall's discovery has contributed to a deeper understanding of fundamental life processes such as cell division, growth and death. Insights into TOR signaling pathways and their involvement in disease have opened the door for new therapeutic strategies for cancer, obesity, diabetes, and cardiovascular disease. Pharmacological inhibition of TOR also helps patients accept transplanted organs.

Bio
Michael N. Hall was born (1953) in Puerto Rico and grew up in South America (Venezuela and Peru). He received his Ph.D. from Harvard University and was a postdoctoral fellow at the Pasteur Institute (Paris, France) and the University of California, San Francisco. He joined the Biozentrum of the University of Basel (Switzerland) in 1987 where he is currently Professor and former Chair of Biochemistry. Hall is a pioneer in the fields of TOR signaling and cell growth control. In 1991, Hall and colleagues discovered TOR (Target of Rapamycin) and subsequently elucidated its role as a central controller of cell growth and metabolism. TOR is a conserved, nutrient- and insulin-activated protein kinase. The discovery of TOR led to a fundamental change in how one thinks of cell growth. It is not a spontaneous process that just happens when building blocks (nutrients) are available, but rather a highly regulated, plastic process controlled by TOR-dependent signaling pathways. As a central controller of cell growth and metabolism, TOR plays a key role in development and aging, and is implicated in disorders such as cancer, cardiovascular disease, diabetes, and obesity. Hall is a member of the US National Academy of Sciences, has received numerous awards, including the Cloëtta Prize for Biomedical Research (2003), the Louis-Jeantet Prize for Medicine (2009), the Marcel Benoist Prize for Sciences or Humanities (2012), and the Breakthrough Prize in Life Sciences (2014), and has served on several editorial and scientific advisory boards. He and his wife Sabine (née Carrère) live in Basel with their daughters Zoé and Léa.

The work: Dr. Cantley’s research focuses on understanding the pathways that regulate normal cell growth and the defects that cause cell transformation leading to cancer. Along with colleagues he discovered a growth signaling molecule called phosphoinositide 3-kinase (PI3K), a key factor in tumor growth. His discovery showcased a new language of how cells control themselves internally.

The impact: He has worked to identify new treatments for cancers that result from defects in the pathway. His discovery has resulted in various treatments for personalized cancer therapy and diabetes.

Bio
Lewis C. Cantley, Ph.D., is the Margaret and Herman Sokol Professor and Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medical College/New York Presbyterian Hospital. Dr. Cantley grew up in West Virginia and graduated from West Virginia Wesleyan College in 1971. He obtained a Ph.D. in biophysical chemistry from Cornell University in 1975 and did postdoctoral training at Harvard University. Prior to taking the position at Weill Cornell, he taught and did research in biochemistry, physiology and cancer biology in Boston, most recently at Beth Israel Deaconess Medical Center and Harvard Medical School. His laboratory discovered the PI 3-Kinase pathway that plays a critical role in insulin signaling and in cancers.

Dr. Cantley was elected to the American Academy of Arts and Sciences in 1999 and to the National Academy of Sciences in 2001. Among his other awards are the ASBMB Avanti Award for Lipid Research in 1998, the Heinrich Weiland Preis for Lipid Research in 2000, the Caledonian Prize from the Royal Society of Edinburgh in 2002, the 2005 Pezcoller Foundation–AACR International Award for Cancer Research, the 2009 Rolf Luft Award for Diabetes and Endocrinology Research from the Karolinska Institute, Stockholm, the 2011 Pasrow Prize for Cancer Research, the 2013 Breakthrough in Life Sciences Prize and the 2013 Jacobaeus Prize for Diabetes Research from the Karolinska Institute. Elected into the Institute of Medicine 2014.

The work: In the 1980s, HIV/AIDS was largely viewed as a homosexual disease. Throughout the 1980s, Dr. Frank Plummer conducted research, facilitated by the University of Manitoba, on a large cohort of Nairobi sex workers which found that two thirds of them had HIV/AIDS which was astonishing at the time. He also showed that about ten percent of these sex workers remain HIV uninfected despite multiple exposures. This identification of natural resistance to HIV has guided vaccine development strategies. He further went on to conduct work on mechanisms of resistance to HIV, risk factors for heterosexual transmission of HIV, mother-to-child transmission of HIV and developed public health strategies for control of sexually transmitted infections. Further research showed that many groups in addition to these female sex workers are immune to HIV. Over the next 16 years, Dr. Plummer remained in Nairobi, and this led to a series of investigations, international collaborations and some very important discoveries about the susceptibility to HIV infection and transmissibility.

The impact: His original and sustained contributions in this field have led to innovative strategies for HIV prevention at an internationally recognized level, and are being used around the world to prevent many thousands of HIV infections. Dr. Plummer, Distinguished Professor, University of Manitoba, is a pioneering HIV/AIDS researcher thanks to not only his ground-breaking work but also his leadership as Scientific Director General at the National Microbiology Laboratory in Winnipeg leading their response to numerous outbreaks including his support and contributions to the development of the Ebola vaccine programs in Canada, SARS treatment in 2003 and the 2009 H1N1 pandemic influenza outbreak.

Bio
Dr. Plummer is a native Manitoban and received his medical degree from the University of Manitoba in 1976. He trained in internal medicine and infectious diseases at the University of Southern California, the University of Manitoba, the University of Nairobi, and the Centers for Disease Control in Atlanta. He joined the University of Manitoba faculty in 1984 and spent 17 years in Nairobi as the leader of the world-renowned Manitoba Nairobi collaboration. From 2000-2014 he was Scientific Director of the National Microbiology Laboratory in Winnipeg, building it into a globally preeminent public health laboratory.

Dr. Plummer is recognized internationally for his work in public health and science, having published over 375 high impact original articles. He has received numerous honors, including; Officer of the Order of Canada, Order of Manitoba, Killam Prize; Prix Galien; two honorary degrees.; Rh Institute Award; Achievement Award from the American Venereal Disease Association; I.S. Ravdin Award, American College of Surgeons; St. Boniface Hospital Research Foundation International Award; Canadian Institutes of Health Research Researcher of the Year 2007; Scopus Award, Hebrew University of Jerusalem. He has been elected to the American Society of Clinical Investigation and the Association of American Physicians and advised has the National Academy of Sciences in the US, the World Bank, the World Health Organization, and the Governments of Kenya, India and Lesotho.

The work:

Dr. Fauci has made critical contributions to the understanding of how HIV destroys the body’s immune defenses. His defining research on the mechanisms of HIV disease along with his work on developing and testing drug therapies have been highly influential in establishing the scientific basis for effective HIV therapies and prevention modalities for patients living with HIV/AIDS.

The impact:

As a testament to his extraordinary research accomplishments, Dr. Fauci was ranked in a 2015 analysis of Google Scholar citations as the 14th most highly cited researcher of all time, dead or alive, in any field. In addition to his own individual contributions to science, Dr. Fauci has served as Director of the USA National Institute of Allergy and Infectious Diseases (NIAID) for 32 years. In this role he has been a major driving force and thought leader in the biomedical research response to infectious diseases that have devastated many regions of the developing world. He has been a key figure in marshalling U.S. government support for and directing research that led to the development of the antiretroviral drug combinations that have transformed the lives of HIV-infected individuals, providing many with an essentially normal life expectancy. One of Dr. Fauci’s most important accomplishments was his role as the principal architect of the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), which over the past 13 years has been responsible for saving the lives of millions of HIV-infected individuals and preventing millions of HIV infections through the developing world, particularly in sub-Saharan African.

Bio
Anthony S. Fauci, M.D., is director of the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health. Since his appointment as NIAID director in 1984, Dr. Fauci has overseen an extensive research portfolio devoted to preventing, diagnosing, and treating infectious and immune-mediated diseases. Dr. Fauci also is chief of the NIAID Laboratory of Immunoregulation, where he has made numerous important discoveries related to HIV/AIDS and is one of the most-cited scientists in the field. Dr. Fauci serves as one of the key advisors to the White House and Department of Health and Human Services on global AIDS issues, and on initiatives to bolster medical and public health preparedness against emerging infectious disease threats such as Ebola and pandemic influenza. He was one of the principal architects of the President’s Emergency Plan for AIDS Relief (PEPFAR), which has already been responsible for saving millions of lives throughout the developing world.

Dr. Fauci is a member of the US National Academy of Sciences and is the recipient of numerous prestigious awards for his scientific and global health accomplishments, including the National Medal of Science, the Mary Woodard Lasker Award for Public Service, and the Presidential Medal of Freedom. He has been awarded 42 honorary doctoral degrees and is the author, coauthor, or editor of more than 1,280 scientific publications, including several major textbooks.

The work: Dr. Barrangou and Dr. Horvath’s research focused on understanding the genetic basis for health-promoting and technological properties of beneficial bacteria used in food fermentations. Along with colleagues, they established that CRISPR-Cas systems provide adaptive immunity against viruses in bacteria where it recognizes foreign DNA and uses a special molecular scalpel to target and destroy it. They also showed that CRISPR arrays capture viral DNA for natural vaccination against bacteriophages; and demonstrated that cas genes are implicated in sequence-specific targeting and cleavage of DNA.

The impact: Their discovery established CRISPR-Cas as the adaptive immune system of bacteria and has made dramatic impact on the science community, setting the stage for a new research area. This inspired others to investigate CRISPR further. The key advantages of CRISPR over other gene-editing systems are its ability to be quick, precise, efficient and relatively inexpensive. And, as the scientific community has shown over the past few years it is transferable to many types of living organisms. The list of possible applications includes: genome editing, antibacterial and antimicrobial production, food safety, food production and plant breeding.

Bio
Rodolphe Barrangou is an Associate Professor in the Department of Food, Bioprocessing and Nutrition Sciences at North Carolina State University, a NC State University Scholar, and the Todd R. Klaenhammer Distinguished Scholar in Probiotics Research. Dr. Barrangou is also an associate member of the Microbiology graduate program, the Biotechnology graduate program, the Functional Genomics graduate program, and the Center for Integrative Medicine. Dr. Barrangou is also an adjunct member of the Food Science Department at the Pennsylvania State University.

His CRISPR laboratory focuses on the evolution and functions of CRISPR-Cas systems, and their use for bacterial genotyping, building prokaryotic immunity, and Cas9-mediated genome editing in lactic acid bacteria used in food manufacturing.

Dr. Barrangou earned a BS in Biological Sciences from the Rene Descartes University in Paris, France; a MS in Biological Engineering from the University of Technology in Compiegne, France; a MS in Food Science from NC State University; a PhD in Genomics from NC State University; and a MBA from the University of Wisconsin-Madison. Dr. Barrangou and colleagues at DuPont established the biological role of CRISPR-Cas systems in adaptive immunity in bacteria, and used CRISPR-based technologies for bacterial genotyping of industrial cultures, and for the vaccination of dairy cultures against bacteriophages. After nine years in R&D and M&A at Danisco and DuPont, he joined the faculty at NC State University in 2013.

Dr. Barrangou is the recipient of the 2014 NC State Alumni Association Outstanding Research Award, and of the 2015 NC State Faculty Scholars Award. He has been on the Thomson Reuters Highly Cited Researchers list in 2014 and 2015. Dr. Barrangou is on the board of directors of Caribou Biosciences, a co-founder and member of the Scientific Advisory Board of Intellia Therapeutics, and a founding investor of Locus Biosciences.

Dr. Barrangou has published numerous articles on CRISPR-Cas systems and their use since 2005, including establishing their role as bacterial immune systems, and exploiting them for industrial applications. Following the initial work unraveling the biological function of CRISPR arrays and cas genes, subsequent studies and collaborative efforts identified PAMs as critical sequences for phage DNA targeting, showed that Cas9 is an endonuclease which can cleave plasmid and phage DNA, and provided the first proof of concept that CRISPR can be reprogrammed and transferred heterologously. Dr. Barrangou also established and co-hosted five international CRISPR meetings, and edited the first book on CRISPR-Cas systems.

The work: Dr. Barrangou and Dr. Horvath’s research focused on understanding the genetic basis for health-promoting and technological properties of beneficial bacteria used in food fermentations. Along with colleagues, they established that CRISPR-Cas systems provide adaptive immunity against viruses in bacteria where it recognizes foreign DNA and uses a special molecular scalpel to target and destroy it. They also showed that CRISPR arrays capture viral DNA for natural vaccination against bacteriophages; and demonstrated that cas genes are implicated in sequence-specific targeting and cleavage of DNA.

The impact: Their discovery established CRISPR-Cas as the adaptive immune system of bacteria and has made dramatic impact on the science community, setting the stage for a new research area. This inspired others to investigate CRISPR further. The key advantages of CRISPR over other gene-editing systems are its ability to be quick, precise, efficient and relatively inexpensive. And, as the scientific community has shown over the past few years it is transferable to many types of living organisms. The list of possible applications includes: genome editing, antibacterial and antimicrobial production, food safety, food production and plant breeding.

Bio
Philippe Horvath is a senior scientist at DuPont. He graduated from Université Louis-Pasteur, Strasbourg, France in 1996 and obtained his Ph.D. in Cellular and Molecular Biology in 2000. That same year, he was recruited by Rhodia Food and worked at the R&D center in Dangé-Saint-Romain, France, where he contributed to the development of molecular biology tools for bacterial strain screening, microbial identification, and typing of lactic acid bacteria and their bacteriophages.

Philippe became senior scientist in 2006, two years after Rhodia Food was acquired by the Danish company Danisco, a world leader in specialty food ingredients. In 2014, three years after DuPont acquired Danisco, Philippe was appointed Associate to the DuPont Fellows Forum, and further appointed DuPont Nutrition & Health Technical Fellow in 2015.

Since late 2002, a large part of Philippe’s research activities has been dedicated to CRISPR (clustered regularly interspaced short palindromic repeats), first as a polymorphic chromosomal region useful for strain differentiation and tracking, and then as a bacterial immune system with considerable industrial, biotechnological, and medical applications. Philippe is co-inventor of 95 patents and/or patent applications, of which 62 are related to various uses of CRISPR, and co-author of 31 peer-reviewed articles (22 about CRISPR) and 4 book chapters. Together with other scientists in the company, Philippe was recognized with the 2008 Danisco Innovation Award, and with the 2013 Bolton/Carothers Innovative Science Award. In addition to being selected as a 2015 Thomson Reuters Highly Cited Researcher, Philippe was awarded with the 2015 Massry Prize.

The work: In 2012 Dr. Charpentier and Dr. Doudna published the description of a revolutionary new genome editing technology that uses an engineered single-guide RNA together with the DNA-cleaving enzyme Cas9 to readily manipulate the genomic DNA of individual cells. The CRISPR-Cas9 technology has given biologists the equivalent of a molecular surgery kit for routinely disabling, activating or altering genes with high efficiency and precision. Their collective work has led to the breakthrough discovery of DNA cleavage by Cas9, a dual RNA- guided enzyme whose ability to cut double-stranded DNA can be programmed by changing the guide RNA sequence. Recognizing that such an activity could be employed as a molecular tool for precision genome engineering in various kinds of cells, their teams redesigned the natural dual-RNA guide as a single-guide RNA (sgRNA), creating an easy-to-use two component system.

The impact: This technology is transforming the fields of molecular genetics, genomics, agriculture and environmental biology. RNA-guided Cas9 complexes are effective genome engineering agents in animals, plants, fungi and bacteria. The CRISPR-Cas9 technology is being used in thousands of laboratories around the world to advance biological research by engineering cells and organisms in precise ways.

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Emmanuelle Charpentier is Scientific Member of the Max Planck Society and Director at the Max Planck Institute for Infection Biology in Berlin, Germany. She is Alexander von Humboldt Professor in Germany and Visiting Professor at Umeå University in Sweden. E. Charpentier is recognized as a world-leading expert in regulatory mechanisms underlying processes of infection and immunity in bacterial pathogens. With her recent groundbreaking findings in the field of RNA-mediated regulation based on the CRISPR-Cas9 system, E. Charpentier has laid the foundation for the development of a novel, highly versatile and specific genome editing technology that is revolutionizing life sciences research and could open up whole new opportunities in biomedical gene therapies. The resulting field of research is now developing at dazzling speed, with exciting new aspects emerging almost weekly. E. Charpentier is Elected Foreign Member of The Royal Swedish Academy of Sciences, Elected Member of the German National Academy of Sciences, Elected Member of the European Academy of Microbiology, Elected Fellow of the American Academy of Microbiology and Elected EMBO Member. E. Charpentier has been awarded prestigious honors including an Honorary Doctorate of the New York University, the Paul Ehrlich and Ludwig Darmstaedter Prize 2016, French Chevalier Order de la Légion d’Honneur in 2016, Leibniz Prize 2016, the Otto Warburg Medal 2016, the L’Oréal-UNESCO For Women in Science Award 2016, the Carus-Medal of the German National Academy of Sciences Leopoldina 2015, the Gruber Prize in Genetics 2015, the Princess of Asturias Award for Technical and Scientific Research 2015, the 2015 Louis Jeantet Prize for Medicine, the 2015 Ernst Jung Prize for Medicine, the 2015 Breakthrough Prize in Life Sciences, the 2014 Grand Prix Jean-Pierre LeCocq and the 2014 Göran Gustafsson Prize. The impact of her scientific accomplishments has also been recognized in the broader community of world affairs. E. Charpentier was selected as one of TIME’s 100 Most Influential People in the World in 2015, one of Foreign Policy’s 100 Leading Global Thinkers in 2014, one of Vanity Fair’s 50 most influential French people worldwide in 2014 and 2015. E. Charpentier is inventor and co-owner of seminal intellectual property comprising the CRISPR-Cas9 technology, and co-founder of CRISPR Therapeutics and ERS Genomics, created to facilitate the development of the CRISPR-Cas9 genome engineering technology for biotechnological and biomedical purposes.

The work: In 2012 Dr. Charpentier and Dr. Doudna published the description of a revolutionary new genome editing technology that uses an engineered single-guide RNA together with the DNA-cleaving enzyme Cas9 to readily manipulate the genomic DNA of individual cells. The CRISPR-Cas9 technology has given biologists the equivalent of a molecular surgery kit for routinely disabling, activating or altering genes with high efficiency and precision. Their collective work has led to the breakthrough discovery of DNA cleavage by Cas9, a dual RNA- guided enzyme whose ability to cut double-stranded DNA can be programmed by changing the guide RNA sequence. Recognizing that such an activity could be employed as a molecular tool for precision genome engineering in various kinds of cells, their teams redesigned the natural dual-RNA guide as a single-guide RNA (