X
Online Event
Symposia
Gairdner Science Week 2022 Symposium
October 26, 2022
9:00 AM

WATCH LIVE HERE

Changing views of the hematopoietic stem cell: lineage bias, clonal hematopoiesis and impact on disease

Join us on October 26 from 9 a.m. to 12:30 p.m. EDT for our annual Gairdner Science Week Symposium, live and IN-PERSON for the first time in nearly three years.

Inspired by the work of 2022 Canada Gairdner International Award laureate, Dr. John Dick, this symposium will bring together some of the world’s top researchers in the field of blood stem cells. It will explore the evolution over the years of the concept of the multipotent blood stem cell first put forward by Till and McCulloch and how this has impacted our understanding of blood-borne diseases.

Tickets available for both IN-PERSON and VIRTUAL.




Event Information

october, 2022

october, 2022

202226oct9:00 am12:30 pmGairdner Science Week 2022 Symposium

Event Details

WATCH LIVE HERE

Changing views of the hematopoietic stem cell: lineage bias, clonal hematopoiesis and impact on disease

Join us on October 26 from 9 a.m. to 12:30 p.m. EDT for our annual Gairdner Science Week Symposium, live and IN-PERSON for the first time in nearly three years.

Inspired by the work of 2022 Canada Gairdner International Award laureate, Dr. John Dick, this symposium will bring together some of the world’s top researchers in the field of blood stem cells. It will explore the evolution over the years of the concept of the multipotent blood stem cell first put forward by Till and McCulloch and how this has impacted our understanding of blood-borne diseases.

Tickets available for both IN-PERSON and VIRTUAL.

Time

(Wednesday) 9:00 am - 12:30 pm

Location

MaRS Discovery District

101 College Street, Toronto, ON. M5G 1L7

Contact (E-mail or link)

events@gairdner.org

RSVP (E-mail or link)

https://www.eventbrite.ca/e/gairdner-science-week-2022-symposium-tickets-376818744007

Speakers for this event

  • Dr. Benjamin Ebert

    Dr. Benjamin Ebert

    Chair of Medical Oncology at the Dana-Farber Cancer Institute George P. Canellos, MD and Jean S. Canellos Professor of Medicine at Harvard Medical School Howard Hughes Medical Institute Investigator Institute Member of the Broad Institute.

    Dr. Benjamin Ebert is the Chair of Medical Oncology at the Dana-Farber Cancer Institute, the George P. Canellos, MD and Jean S. Canellos Professor of Medicine at Harvard Medical School, a Howard Hughes Medical Institute Investigator, and an Institute Member of the Broad Institute.

    The Ebert laboratory focuses on the molecular basis and treatment of hematologic malignancies and its non-malignant precursor conditions, with a particular focus on myelodysplastic syndromes (MDS) and clonal hematopoiesis. The Ebert laboratory demonstrated that lenalidomide, a derivative of thalidomide, binds the CRL4-CRBN E3 ubiquitin ligase and induces degradation of specific substrates. Subsequent research from the Ebert laboratory has examined the potential of thalidomide analogs to induce degradation of a broad array of zinc finger transcription factors and other proteins, and to identify novel mechanisms of drug-induced protein degradation.

    Dr. Ebert is an elected member of the National Academy of Medicine, the American Society for Clinical Investigation and the Association of American Physicians. He served as President of the American Society for Clinical Investigation in 2017. He received the William Dameshek Prize from the American Society of Hematology in 2017, the Meyenburg Prize for Cancer Research in 2019, the Sjöberg Prize from the Royal Swedish Academy of Sciences in 2021, and the Korsmeyer Award from the American Society for Clinical Investigation in 2021.

    Chair of Medical Oncology at the Dana-Farber Cancer Institute George P. Canellos, MD and Jean S. Canellos Professor of Medicine at Harvard Medical School Howard Hughes Medical Institute Investigator Institute Member of the Broad Institute.

  • Dr. David Scadden

    Dr. David Scadden

    Gerald and Darlene Jordan Professor of Medicine, Harvard University; Professor and Chair emeritus, Harvard University Department of Stem Cell and Regenerative Biology; Co-founder and co-director, Harvard Stem Cell Institute; Hematologist/Oncologist, Massachusetts General Hospital

    David Scadden is the Gerald and Darlene Jordan Professor of Medicine at Harvard University. He is Professor and Chair emeritus of the Harvard University Department of Stem Cell and Regenerative Biology. He co-founded and co-directs the Harvard Stem Cell Institute with Prof. Douglas Melton. He is a hematologist/oncologist at the Massachusetts General Hospital where he founded and directs the Center for Regenerative Medicine and previously led the Hematologic Malignancies Program of the MGH Cancer Center. He is a member or fellow of the National Academy of Medicine, the American Academy of Arts and Sciences, the American Association for the Advancement of Science, the American College of Physicians, and a former member of the Board of External Experts for the National Heart, Lung and Blood Institute and the National Cancer Institute’s Board of Scientific Counselors. He is an Affiliate Member of the Broad Institute of Harvard and MIT and a Visiting Scholar of Pembroke College, University of Cambridge, England. He co-founded the public companies, Fate Therapeutics and Magenta Therapeutics and is a Director of Agios Pharmaceuticals and Editas Medicines. His work emphasizes using multidisciplinary approaches to define novel therapies for blood diseases. He is credited with having first experimentally defined a mammalian stem cell niche and its role in malignancy. His work on blood stem cells has led to new approaches to bone marrow transplantation now in clinical trial. He received the E. Donnall Thomas Award from the American Society of Hematology for his ‘pioneering work on the bone marrow microenvironment.’

    Gerald and Darlene Jordan Professor of Medicine, Harvard University; Professor and Chair emeritus, Harvard University Department of Stem Cell and Regenerative Biology; Co-founder and co-director, Harvard Stem Cell Institute; Hematologist/Oncologist, Massachusetts General Hospital

  • Dr. Emmanuelle Passegué

    Dr. Emmanuelle Passegué

    Endowed Alumni Professor of Genetics & Development and the Director of the Columbia Stem Cell Initiative (CSCI), Columbia University Irving Medical Center (CUIMC)

    Dr. Emmanuelle Passegué, Ph.D. is the endowed Alumni Professor of Genetics & Development and the Director of the Columbia Stem Cell Initiative (CSCI) at Columbia University Irving Medical Center (CUIMC) in New York City. Dr. Passegué received her Ph.D. from the University Paris XI (France), and trained with Dr. Erwin Wagner (Institute for Molecular pathology, Vienna, Austria) and Dr. Irv Weissman (Stanford University, USA) before joining the University of California San Francisco (UCSF) in 2005. Dr. Passegué was a Professor of Medicine in the Hematology/Oncology Division and the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCSF until 2016 before joining Columbia University in January 2017. Her research investigates the biology of blood-forming hematopoietic stem cells in normal and deregulated contexts such as hematological malignancies and physiological aging. Dr. Passegué has received a number of awards and prizes including a Scholar Award from the Lymphoma and Leukemia Society, an Outstanding Investigator Award from the NHLBI, and the 2019 William Dameshek Prize from the American Society of Hematology.

    Endowed Alumni Professor of Genetics & Development and the Director of the Columbia Stem Cell Initiative (CSCI), Columbia University Irving Medical Center (CUIMC)

  • Dr. Margaret Goodell

    Dr. Margaret Goodell

    Professor and Chair of the Department of Molecular and Cellular Biology, and Director of the Stem Cells and Regenerative Medicine Center, Baylor College of Medicine

    Margaret (“Peggy”) Goodell is Professor and Chair of the Department of Molecular and Cellular Biology, and Director of the Stem Cells and Regenerative Medicine Center, at Baylor College of Medicine, in Houston, Texas. Goodell’s research is focused on the mechanisms that regulate hematopoietic stem cells, and their dysregulation in malignancies, particularly DNA Methyltransferase 3A (DNMT3A). Goodell was elected to the National Academy of Medicine in 2019. She is a recipient of the Tobias Award from the International Society for Stem Cell Research (2020), the Damashek Prize from the American Society of Hematology (2012), the Edith and Peter O’Donnell Award in Medicine from TAMEST (2011). Goodell is Chair of the Scientific Advisory Board of the Keystone Symposia and is a member of their Board of Directors. Goodell is a former president of the International Society for Experimental Hematology (2013). She currently serves on the editorial boards of Cell Stem Cell and Cancer Cell has served on the editorial board of PLoS Biology, and as an Associated Editor of Blood. Goodell directs a laboratory of about 15 trainees.

    Professor and Chair of the Department of Molecular and Cellular Biology, and Director of the Stem Cells and Regenerative Medicine Center, Baylor College of Medicine

  • Jim Woodgett

    Jim Woodgett

    Principal Investigator, Lunenfeld-Tanenbaum Research Institute

    Principal Investigator, Lunenfeld-Tanenbaum Research Institute

  • John E. Dick

    John E. Dick

    Canada Gairdner International Award 2022; Senior Scientist and Canada Research Chair in Stem Cell Biology, Princess Margaret Cancer Centre, UHN; University Professor, Department of Molecular Genetics, University of Toronto

    Canada Gairdner International Award 2022; Senior Scientist and Canada Research Chair in Stem Cell Biology, Princess Margaret Cancer Centre, UHN; University Professor, Department of Molecular Genetics, University of Toronto

    Canada Gairdner International Award 2022; Senior Scientist and Canada Research Chair in Stem Cell Biology, Princess Margaret Cancer Centre, UHN; University Professor, Department of Molecular Genetics, University of Toronto

  • Prof. Ana Cvejic

    Prof. Ana Cvejic

    Professor, University of Copenhagen; Group leader, Biotechnology Research and Innovation Centre (BRIC)

    Ana Cvejic is a Professor at the University of Copenhagen and a Group leader at the Biotechnology Research and Innovation Centre (BRIC), Denmark. In 2008 Ana received her PhD in Biochemistry at the University of Bristol. She then moved to the University of Cambridge/Wellcome Trust Sanger Institute to start a Postdoctoral Fellowship, with Professor Willem Ouwehand. In 2012 Ana was awarded the CRUK Career Development Fellowship to start her independent group at the University of Cambridge. In 2015 Ana was awarded ERC Starting Grant and in 2016 EMBO Young Investigator award. In 2022 Ana was a recipient of the ERC Consolidator Grant and she moved her group to the University of Copenhagen. With the principal expertise and research interest in the molecular regulation of blood stem cell fate choices her research sits at the intersection of molecular biology, genetics and systems biology and it closely couples experimental approaches and “big” biological data analysis.

    Professor, University of Copenhagen; Group leader, Biotechnology Research and Innovation Centre (BRIC)

  • Prof. Sten Eirik W. Jacobsen

    Prof. Sten Eirik W. Jacobsen

    Professor of Stem Cell Biology and Regenerative Medicine, Karolinska Institutet and University of Oxford

    Sten Eirik W. Jacobsen, MD, PhD, is a Professor of Stem Cell Biology and Regenerative Medicine at the Karolinska Institutet and at the University of Oxford. His research is focused at understanding how normal blood cell formation from stem cells in the bone marrow is organized and regulated to ensure replenishment of millions of blood cells per second, and how normal stem cells upon acquisition of oncogenic mutations are transformed into malignant stem cells. The aim is to unravel the dynamics of stem and progenitor cells in unperturbed hematopoiesis, and to identify and therapeutically target key cellular and molecular events in the transformation from normal to malignant hematopoiesis. Through these research directions the goal is to identify novel therapeutic strategies towards regenerative hematopoiesis and targeting of leukemic stem cells.

    Professor of Stem Cell Biology and Regenerative Medicine, Karolinska Institutet and University of Oxford

  • Prof. Tsvee Lapidot

    Prof. Tsvee Lapidot

    Professor of Stem Cell Biology and Regenerative Medicine at the Weizmann Institute, Dept. of Immunology and Regenerative Biology, Rehovot Israel.

    Tsvee Lapidot Ph.D is a Professor of Stem Cell Biology and Regenerative Medicine at the Weizmann Institute, Dept. of Immunology and Regenerative Biology, Rehovot Israel. His research is focused at understanding how the daily replenishment of the blood with new mature blood and immune cells with a finite lifespan by the reservoir of bone marrow retained hematopoietic stem and progenitor cells is metabolically regulated and controlled. In addition, his research is focused on how the bone marrow reservoir of immature and maturing blood and immune cells is daily replenished, including hematopoietic stem cell self-renewal. Since only the most primitive hematopoietic stem cells which are bone marrow retained and functionally express the endothelial receptor EPCR are chemotherapy resistant, the mechanism and players involved are also investigated. These studies include the role of daily circadian light and darkness onset, the darkness hormone melatonin and PGE2 as well as the role of transient elevations in bone marrow norepinephrine, TNF and ROS levels. The blood bone marrow endothelial barrier and its dynamic permeability, osteoclast/osteoblast mediated bone turnover and the dynamic bone marrow stem cell niches. The essential roles of the universal stem cell chemokine SDF-1 (also termed CXCL12) which is highly expressed by bone marrow osteoblasts, capillaries and arterioles in the stem cell niches and its major receptor CXCR4 functionally expressed by hematopoietic stem and progenitor cells. Finally, the essential roles of CXCL12/CXCR4 interactions and coagulation related aPC/EPCR/PAR1 interactions in both human and mouse hematopoietic stem cell chemotherapy resistance with clinical relevance including in human EPCR positive and chemotherapy resistant Leukemic stem cells obtained from AML patients, which are also studied.

    Professor of Stem Cell Biology and Regenerative Medicine at the Weizmann Institute, Dept. of Immunology and Regenerative Biology, Rehovot Israel.

Schedule

    • october 26, 2022
    • 9:00 a.m. Session 1: Opening Remarks9:00 a.m. - 9:05 a.m.Chair Dr. Jim WoodgettSpeakers: Jim Woodgett

    • 9:05 a.m. "Alternative pathways of platelet replenishment by distinct hematopoietic stem cells"9:05 a.m. - 9:30 a.m.Rare multipotent hematopoietic stem cells (HSCs) in adult bone marrow with extensive self-renewal potential possess the ability to secure life-long and efficient replenishment of all myeloid and lymphoid blood cell lineages, in steady-state as well as following major physiological and clinical challenges, including blood lineage replenishment following bone marrow ablation. Establishing the normal lineage restriction pathways from fully multipotent HSCs to progenitors irreversibly committed to a single blood cell lineage remains an important goal towards unravelling the regulation of normal blood lineage development, and how this is perturbed in hematological malignancies. Using highly sensitive tracking of progenitors and mature cells of the myeloid, B and T cell as well megakaryocyte/platelet and erythroid lineages, produced from singly transplanted mouse HSCs, we recently uncovered a highly organized, predictable and stable framework for lineage-restricted fates of long-term (LT) self-renewing HSCs following transplantation into myeloablated recipients (Nature 554:106-111, 2018). Most notably, a distinct class of LT-HSCs adopted a fate towards effective and stable replenishment of a megakaryocyte/platelet-lineage tree but not any other blood cell lineages, despite their sustained multipotency. No self-renewing LT-HSCs contributed exclusively to any other single blood-cell lineage, and platelets were the only blood cells consistently replenished by all multipotent HSCs. In more recent and ongoing studies we have obtained experimental evidence in support of platelets being replenished through alternative lineage restriction pathways, initiated by HSCs with distinct lineage biases.Speakers: Prof. Sten Eirik W. Jacobsen

    • 9:32 a.m. "Clonal hematopoiesis and the origin of blood cancer"9:32 a.m. - 9:55 a.m."Clonal hematopoiesis and the origin of blood cancer"Speakers: Dr. Benjamin Ebert

    • 9:57 a.m. "Investigating Human Foetal Blood Development at the Single-Cell Level"9:57 a.m. - 10:22 a.m.Professor Ana Cvejic is a Professor at the University of Copenhagen and a Group leader at the Biotechnology Research and Innovation Centre (BRIC), Denmark. In 2008 Ana received her PhD in Biochemistry at the University of Bristol. She then moved to the University of Cambridge/Wellcome Trust Sanger Institute to start a Postdoctoral Fellowship, with Professor Willem Ouwehand. In 2012 Ana was awarded the CRUK Career Development Fellowship to start her independent group at the University of Cambridge. In 2015 Ana was awarded ERC Starting Grant and in 2016 EMBO Young Investigator award. In 2022 Ana was a recipient of the ERC Consolidator Grant and she moved her group to the University of Copenhagen. With the principal expertise and research interest in the molecular regulation of blood stem cell fate choices her research sits at the intersection of molecular biology, genetics and systems biology and it closely couples experimental approaches and “big” biological data analysis.Speakers: Prof. Ana Cvejic

    • 10:25 a.m. "Deregulated Hematopoietic Stem Cell Behavior in Aging and Malignancies"10:25 a.m. - 10:50 a.m.Aging of the hematopoietic system promotes various blood, immune and systemic disorders and is largely driven by hematopoietic stem cells (HSC) dysfunction. An evolving understanding of HSC fate decision mechanisms and regulations by the bone marrow niche microenvironment has provide new opportunities to target aberrant behaviors during aging and disease development. In this context, we have identified several approaches to improve the regenerative capacity of aged HSCs and rebalance blood production with age.Speakers: Dr. Emmanuelle Passague

    • 10:50 a.m. Break10:50 a.m. - 11:00 a.m.Break

    • 11:00 a.m. Session 2: Opening Remarks11:00 a.m. - 11:02 a.m.Chair Dr. John DickSpeakers: John E. Dick, John E. Dick

    • 11:02 a.m. "Regenerating T cell immunity"11:02 a.m. - 11:27 a.m.The thymus is critical for T cell generation, but it undergoes involution beginning in puberty leading to gradual attrition in the T cell repertoire. The result is life threatening vulnerability to infection with acute immune injury and increased incidence of virus reactivation, malignancy and autoimmunity with age. Thymic activity can be enhanced by increased blood precursors reaching it. We have identified two approaches to increasing the supply chain of cells entering the thymus that foster immune rejuvenation.Speakers: Dr. David Scadden

    • 11:29 a.m. "Winning Strategies for the Hematopoietic Stem Cell Ultramarathon"11:29 a.m. - 12:04 a.m.When we are young, hundreds of thousands of hematopoietic stem cells are simultaneously working to regenerate the many cell types of the blood. As we age, one or a few stem cells start dominating blood production, reducing the clonal complexity of the blood dramatically, resulting in a condition termed “clonal hematopoiesis”, or “CH”. CH is ubiquitous in aging individuals, reaching significant frequencies above the age of 70. CH correlates with a higher risk of developing hematologic malignancies as well as mortality due to other age-related diseases. CH is the consequence of life-long competition among stem cells in the bone marrow, such that the progeny of “winning” stem cells become over-represented in the blood. Around 20 genes have been observed to be recurrently mutated among the winners, indicating that certain genetic variants confer a competitive advantage over many years. The mechanisms through which these variant stem cells triumph are generally poorly understood. Insights into successful strategies may have both prognostic and therapeutic value for CH-associated diseases. The Goodell lab has studied the mechanisms through which variations in the function of DNMT3A, the most common driver of CH, promote winning, establishing the paradigm that enhanced self-renewal offers stem cells a profound advantage over many years. The lab has also studied the mechanisms of through which cells with PPM1D variants win, finding that a minor improvement in resistance to cell death makes stem cells victorious, at least in some contexts. Recently, the lab has considered intrinsic mechanisms that promote advantage of additional variant genes. Surprisingly, all genes studied so far differ slightly in their potency, the molecular mechanisms that confer fitness, and probably the conditions under which they are most likely to triumph. These mechanisms will be compared and discussed, in addition to the interplay between aging, more broadly, and clonal hematopoiesis.Speakers: Dr. Margaret Goodell

    • 12:06 p.m. "Regulation of hematopoietic stem cells and host immunity by light and darkness cues"12:06 p.m. - 12:30 p.m.Hematopoietic stem and progenitor cells (HSPCs) are primarily maintained in an undifferentiated, and quiescent state in the mouse bone marrow (BM). We have recently found that circadian cues regulate daily murine HSPC fate decisions. Daily light and darkness cues induce a fraction of BM HSPCs to differentiate and egress from the BM in daylight to replenish the circulation with mature blood and immune cells. While darkness metabolically elevates their self-renewal to maintain the BM reservoir of undifferentiated HSPC. This topic and regulation of host immunity by circadian light and darkness onset will be discussed.Speakers: Prof. Tsvee Lapidot

202226oct9:00 am12:30 pmGairdner Science Week 2022 Symposium

Event Details

WATCH LIVE HERE

Changing views of the hematopoietic stem cell: lineage bias, clonal hematopoiesis and impact on disease

Join us on October 26 from 9 a.m. to 12:30 p.m. EDT for our annual Gairdner Science Week Symposium, live and IN-PERSON for the first time in nearly three years.

Inspired by the work of 2022 Canada Gairdner International Award laureate, Dr. John Dick, this symposium will bring together some of the world’s top researchers in the field of blood stem cells. It will explore the evolution over the years of the concept of the multipotent blood stem cell first put forward by Till and McCulloch and how this has impacted our understanding of blood-borne diseases.

Tickets available for both IN-PERSON and VIRTUAL.

Time

(Wednesday) 9:00 am - 12:30 pm

Location

MaRS Discovery District

101 College Street, Toronto, ON. M5G 1L7

Contact (E-mail or link)

events@gairdner.org

RSVP (E-mail or link)

https://www.eventbrite.ca/e/gairdner-science-week-2022-symposium-tickets-376818744007

Speakers for this event

  • Dr. Benjamin Ebert

    Dr. Benjamin Ebert

    Chair of Medical Oncology at the Dana-Farber Cancer Institute George P. Canellos, MD and Jean S. Canellos Professor of Medicine at Harvard Medical School Howard Hughes Medical Institute Investigator Institute Member of the Broad Institute.

    Dr. Benjamin Ebert is the Chair of Medical Oncology at the Dana-Farber Cancer Institute, the George P. Canellos, MD and Jean S. Canellos Professor of Medicine at Harvard Medical School, a Howard Hughes Medical Institute Investigator, and an Institute Member of the Broad Institute.

    The Ebert laboratory focuses on the molecular basis and treatment of hematologic malignancies and its non-malignant precursor conditions, with a particular focus on myelodysplastic syndromes (MDS) and clonal hematopoiesis. The Ebert laboratory demonstrated that lenalidomide, a derivative of thalidomide, binds the CRL4-CRBN E3 ubiquitin ligase and induces degradation of specific substrates. Subsequent research from the Ebert laboratory has examined the potential of thalidomide analogs to induce degradation of a broad array of zinc finger transcription factors and other proteins, and to identify novel mechanisms of drug-induced protein degradation.

    Dr. Ebert is an elected member of the National Academy of Medicine, the American Society for Clinical Investigation and the Association of American Physicians. He served as President of the American Society for Clinical Investigation in 2017. He received the William Dameshek Prize from the American Society of Hematology in 2017, the Meyenburg Prize for Cancer Research in 2019, the Sjöberg Prize from the Royal Swedish Academy of Sciences in 2021, and the Korsmeyer Award from the American Society for Clinical Investigation in 2021.

    Chair of Medical Oncology at the Dana-Farber Cancer Institute George P. Canellos, MD and Jean S. Canellos Professor of Medicine at Harvard Medical School Howard Hughes Medical Institute Investigator Institute Member of the Broad Institute.

  • Dr. David Scadden

    Dr. David Scadden

    Gerald and Darlene Jordan Professor of Medicine, Harvard University; Professor and Chair emeritus, Harvard University Department of Stem Cell and Regenerative Biology; Co-founder and co-director, Harvard Stem Cell Institute; Hematologist/Oncologist, Massachusetts General Hospital

    David Scadden is the Gerald and Darlene Jordan Professor of Medicine at Harvard University. He is Professor and Chair emeritus of the Harvard University Department of Stem Cell and Regenerative Biology. He co-founded and co-directs the Harvard Stem Cell Institute with Prof. Douglas Melton. He is a hematologist/oncologist at the Massachusetts General Hospital where he founded and directs the Center for Regenerative Medicine and previously led the Hematologic Malignancies Program of the MGH Cancer Center. He is a member or fellow of the National Academy of Medicine, the American Academy of Arts and Sciences, the American Association for the Advancement of Science, the American College of Physicians, and a former member of the Board of External Experts for the National Heart, Lung and Blood Institute and the National Cancer Institute’s Board of Scientific Counselors. He is an Affiliate Member of the Broad Institute of Harvard and MIT and a Visiting Scholar of Pembroke College, University of Cambridge, England. He co-founded the public companies, Fate Therapeutics and Magenta Therapeutics and is a Director of Agios Pharmaceuticals and Editas Medicines. His work emphasizes using multidisciplinary approaches to define novel therapies for blood diseases. He is credited with having first experimentally defined a mammalian stem cell niche and its role in malignancy. His work on blood stem cells has led to new approaches to bone marrow transplantation now in clinical trial. He received the E. Donnall Thomas Award from the American Society of Hematology for his ‘pioneering work on the bone marrow microenvironment.’

    Gerald and Darlene Jordan Professor of Medicine, Harvard University; Professor and Chair emeritus, Harvard University Department of Stem Cell and Regenerative Biology; Co-founder and co-director, Harvard Stem Cell Institute; Hematologist/Oncologist, Massachusetts General Hospital

  • Dr. Emmanuelle Passegué

    Dr. Emmanuelle Passegué

    Endowed Alumni Professor of Genetics & Development and the Director of the Columbia Stem Cell Initiative (CSCI), Columbia University Irving Medical Center (CUIMC)

    Dr. Emmanuelle Passegué, Ph.D. is the endowed Alumni Professor of Genetics & Development and the Director of the Columbia Stem Cell Initiative (CSCI) at Columbia University Irving Medical Center (CUIMC) in New York City. Dr. Passegué received her Ph.D. from the University Paris XI (France), and trained with Dr. Erwin Wagner (Institute for Molecular pathology, Vienna, Austria) and Dr. Irv Weissman (Stanford University, USA) before joining the University of California San Francisco (UCSF) in 2005. Dr. Passegué was a Professor of Medicine in the Hematology/Oncology Division and the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCSF until 2016 before joining Columbia University in January 2017. Her research investigates the biology of blood-forming hematopoietic stem cells in normal and deregulated contexts such as hematological malignancies and physiological aging. Dr. Passegué has received a number of awards and prizes including a Scholar Award from the Lymphoma and Leukemia Society, an Outstanding Investigator Award from the NHLBI, and the 2019 William Dameshek Prize from the American Society of Hematology.

    Endowed Alumni Professor of Genetics & Development and the Director of the Columbia Stem Cell Initiative (CSCI), Columbia University Irving Medical Center (CUIMC)

  • Dr. Margaret Goodell

    Dr. Margaret Goodell

    Professor and Chair of the Department of Molecular and Cellular Biology, and Director of the Stem Cells and Regenerative Medicine Center, Baylor College of Medicine

    Margaret (“Peggy”) Goodell is Professor and Chair of the Department of Molecular and Cellular Biology, and Director of the Stem Cells and Regenerative Medicine Center, at Baylor College of Medicine, in Houston, Texas. Goodell’s research is focused on the mechanisms that regulate hematopoietic stem cells, and their dysregulation in malignancies, particularly DNA Methyltransferase 3A (DNMT3A). Goodell was elected to the National Academy of Medicine in 2019. She is a recipient of the Tobias Award from the International Society for Stem Cell Research (2020), the Damashek Prize from the American Society of Hematology (2012), the Edith and Peter O’Donnell Award in Medicine from TAMEST (2011). Goodell is Chair of the Scientific Advisory Board of the Keystone Symposia and is a member of their Board of Directors. Goodell is a former president of the International Society for Experimental Hematology (2013). She currently serves on the editorial boards of Cell Stem Cell and Cancer Cell has served on the editorial board of PLoS Biology, and as an Associated Editor of Blood. Goodell directs a laboratory of about 15 trainees.

    Professor and Chair of the Department of Molecular and Cellular Biology, and Director of the Stem Cells and Regenerative Medicine Center, Baylor College of Medicine

  • Jim Woodgett

    Jim Woodgett

    Principal Investigator, Lunenfeld-Tanenbaum Research Institute

    Principal Investigator, Lunenfeld-Tanenbaum Research Institute

  • John E. Dick

    John E. Dick

    Canada Gairdner International Award 2022; Senior Scientist and Canada Research Chair in Stem Cell Biology, Princess Margaret Cancer Centre, UHN; University Professor, Department of Molecular Genetics, University of Toronto

    Canada Gairdner International Award 2022; Senior Scientist and Canada Research Chair in Stem Cell Biology, Princess Margaret Cancer Centre, UHN; University Professor, Department of Molecular Genetics, University of Toronto

    Canada Gairdner International Award 2022; Senior Scientist and Canada Research Chair in Stem Cell Biology, Princess Margaret Cancer Centre, UHN; University Professor, Department of Molecular Genetics, University of Toronto

  • Prof. Ana Cvejic

    Prof. Ana Cvejic

    Professor, University of Copenhagen; Group leader, Biotechnology Research and Innovation Centre (BRIC)

    Ana Cvejic is a Professor at the University of Copenhagen and a Group leader at the Biotechnology Research and Innovation Centre (BRIC), Denmark. In 2008 Ana received her PhD in Biochemistry at the University of Bristol. She then moved to the University of Cambridge/Wellcome Trust Sanger Institute to start a Postdoctoral Fellowship, with Professor Willem Ouwehand. In 2012 Ana was awarded the CRUK Career Development Fellowship to start her independent group at the University of Cambridge. In 2015 Ana was awarded ERC Starting Grant and in 2016 EMBO Young Investigator award. In 2022 Ana was a recipient of the ERC Consolidator Grant and she moved her group to the University of Copenhagen. With the principal expertise and research interest in the molecular regulation of blood stem cell fate choices her research sits at the intersection of molecular biology, genetics and systems biology and it closely couples experimental approaches and “big” biological data analysis.

    Professor, University of Copenhagen; Group leader, Biotechnology Research and Innovation Centre (BRIC)

  • Prof. Sten Eirik W. Jacobsen

    Prof. Sten Eirik W. Jacobsen

    Professor of Stem Cell Biology and Regenerative Medicine, Karolinska Institutet and University of Oxford

    Sten Eirik W. Jacobsen, MD, PhD, is a Professor of Stem Cell Biology and Regenerative Medicine at the Karolinska Institutet and at the University of Oxford. His research is focused at understanding how normal blood cell formation from stem cells in the bone marrow is organized and regulated to ensure replenishment of millions of blood cells per second, and how normal stem cells upon acquisition of oncogenic mutations are transformed into malignant stem cells. The aim is to unravel the dynamics of stem and progenitor cells in unperturbed hematopoiesis, and to identify and therapeutically target key cellular and molecular events in the transformation from normal to malignant hematopoiesis. Through these research directions the goal is to identify novel therapeutic strategies towards regenerative hematopoiesis and targeting of leukemic stem cells.

    Professor of Stem Cell Biology and Regenerative Medicine, Karolinska Institutet and University of Oxford

  • Prof. Tsvee Lapidot

    Prof. Tsvee Lapidot

    Professor of Stem Cell Biology and Regenerative Medicine at the Weizmann Institute, Dept. of Immunology and Regenerative Biology, Rehovot Israel.

    Tsvee Lapidot Ph.D is a Professor of Stem Cell Biology and Regenerative Medicine at the Weizmann Institute, Dept. of Immunology and Regenerative Biology, Rehovot Israel. His research is focused at understanding how the daily replenishment of the blood with new mature blood and immune cells with a finite lifespan by the reservoir of bone marrow retained hematopoietic stem and progenitor cells is metabolically regulated and controlled. In addition, his research is focused on how the bone marrow reservoir of immature and maturing blood and immune cells is daily replenished, including hematopoietic stem cell self-renewal. Since only the most primitive hematopoietic stem cells which are bone marrow retained and functionally express the endothelial receptor EPCR are chemotherapy resistant, the mechanism and players involved are also investigated. These studies include the role of daily circadian light and darkness onset, the darkness hormone melatonin and PGE2 as well as the role of transient elevations in bone marrow norepinephrine, TNF and ROS levels. The blood bone marrow endothelial barrier and its dynamic permeability, osteoclast/osteoblast mediated bone turnover and the dynamic bone marrow stem cell niches. The essential roles of the universal stem cell chemokine SDF-1 (also termed CXCL12) which is highly expressed by bone marrow osteoblasts, capillaries and arterioles in the stem cell niches and its major receptor CXCR4 functionally expressed by hematopoietic stem and progenitor cells. Finally, the essential roles of CXCL12/CXCR4 interactions and coagulation related aPC/EPCR/PAR1 interactions in both human and mouse hematopoietic stem cell chemotherapy resistance with clinical relevance including in human EPCR positive and chemotherapy resistant Leukemic stem cells obtained from AML patients, which are also studied.

    Professor of Stem Cell Biology and Regenerative Medicine at the Weizmann Institute, Dept. of Immunology and Regenerative Biology, Rehovot Israel.

Schedule

    • october 26, 2022
    • 9:00 a.m. Session 1: Opening Remarks9:00 a.m. - 9:05 a.m.Chair Dr. Jim WoodgettSpeakers: Jim Woodgett

    • 9:05 a.m. "Alternative pathways of platelet replenishment by distinct hematopoietic stem cells"9:05 a.m. - 9:30 a.m.Rare multipotent hematopoietic stem cells (HSCs) in adult bone marrow with extensive self-renewal potential possess the ability to secure life-long and efficient replenishment of all myeloid and lymphoid blood cell lineages, in steady-state as well as following major physiological and clinical challenges, including blood lineage replenishment following bone marrow ablation. Establishing the normal lineage restriction pathways from fully multipotent HSCs to progenitors irreversibly committed to a single blood cell lineage remains an important goal towards unravelling the regulation of normal blood lineage development, and how this is perturbed in hematological malignancies. Using highly sensitive tracking of progenitors and mature cells of the myeloid, B and T cell as well megakaryocyte/platelet and erythroid lineages, produced from singly transplanted mouse HSCs, we recently uncovered a highly organized, predictable and stable framework for lineage-restricted fates of long-term (LT) self-renewing HSCs following transplantation into myeloablated recipients (Nature 554:106-111, 2018). Most notably, a distinct class of LT-HSCs adopted a fate towards effective and stable replenishment of a megakaryocyte/platelet-lineage tree but not any other blood cell lineages, despite their sustained multipotency. No self-renewing LT-HSCs contributed exclusively to any other single blood-cell lineage, and platelets were the only blood cells consistently replenished by all multipotent HSCs. In more recent and ongoing studies we have obtained experimental evidence in support of platelets being replenished through alternative lineage restriction pathways, initiated by HSCs with distinct lineage biases.Speakers: Prof. Sten Eirik W. Jacobsen

    • 9:32 a.m. "Clonal hematopoiesis and the origin of blood cancer"9:32 a.m. - 9:55 a.m."Clonal hematopoiesis and the origin of blood cancer"Speakers: Dr. Benjamin Ebert

    • 9:57 a.m. "Investigating Human Foetal Blood Development at the Single-Cell Level"9:57 a.m. - 10:22 a.m.Professor Ana Cvejic is a Professor at the University of Copenhagen and a Group leader at the Biotechnology Research and Innovation Centre (BRIC), Denmark. In 2008 Ana received her PhD in Biochemistry at the University of Bristol. She then moved to the University of Cambridge/Wellcome Trust Sanger Institute to start a Postdoctoral Fellowship, with Professor Willem Ouwehand. In 2012 Ana was awarded the CRUK Career Development Fellowship to start her independent group at the University of Cambridge. In 2015 Ana was awarded ERC Starting Grant and in 2016 EMBO Young Investigator award. In 2022 Ana was a recipient of the ERC Consolidator Grant and she moved her group to the University of Copenhagen. With the principal expertise and research interest in the molecular regulation of blood stem cell fate choices her research sits at the intersection of molecular biology, genetics and systems biology and it closely couples experimental approaches and “big” biological data analysis.Speakers: Prof. Ana Cvejic

    • 10:25 a.m. "Deregulated Hematopoietic Stem Cell Behavior in Aging and Malignancies"10:25 a.m. - 10:50 a.m.Aging of the hematopoietic system promotes various blood, immune and systemic disorders and is largely driven by hematopoietic stem cells (HSC) dysfunction. An evolving understanding of HSC fate decision mechanisms and regulations by the bone marrow niche microenvironment has provide new opportunities to target aberrant behaviors during aging and disease development. In this context, we have identified several approaches to improve the regenerative capacity of aged HSCs and rebalance blood production with age.Speakers: Dr. Emmanuelle Passague

    • 10:50 a.m. Break10:50 a.m. - 11:00 a.m.Break

    • 11:00 a.m. Session 2: Opening Remarks11:00 a.m. - 11:02 a.m.Chair Dr. John DickSpeakers: John E. Dick, John E. Dick

    • 11:02 a.m. "Regenerating T cell immunity"11:02 a.m. - 11:27 a.m.The thymus is critical for T cell generation, but it undergoes involution beginning in puberty leading to gradual attrition in the T cell repertoire. The result is life threatening vulnerability to infection with acute immune injury and increased incidence of virus reactivation, malignancy and autoimmunity with age. Thymic activity can be enhanced by increased blood precursors reaching it. We have identified two approaches to increasing the supply chain of cells entering the thymus that foster immune rejuvenation.Speakers: Dr. David Scadden

    • 11:29 a.m. "Winning Strategies for the Hematopoietic Stem Cell Ultramarathon"11:29 a.m. - 12:04 a.m.When we are young, hundreds of thousands of hematopoietic stem cells are simultaneously working to regenerate the many cell types of the blood. As we age, one or a few stem cells start dominating blood production, reducing the clonal complexity of the blood dramatically, resulting in a condition termed “clonal hematopoiesis”, or “CH”. CH is ubiquitous in aging individuals, reaching significant frequencies above the age of 70. CH correlates with a higher risk of developing hematologic malignancies as well as mortality due to other age-related diseases. CH is the consequence of life-long competition among stem cells in the bone marrow, such that the progeny of “winning” stem cells become over-represented in the blood. Around 20 genes have been observed to be recurrently mutated among the winners, indicating that certain genetic variants confer a competitive advantage over many years. The mechanisms through which these variant stem cells triumph are generally poorly understood. Insights into successful strategies may have both prognostic and therapeutic value for CH-associated diseases. The Goodell lab has studied the mechanisms through which variations in the function of DNMT3A, the most common driver of CH, promote winning, establishing the paradigm that enhanced self-renewal offers stem cells a profound advantage over many years. The lab has also studied the mechanisms of through which cells with PPM1D variants win, finding that a minor improvement in resistance to cell death makes stem cells victorious, at least in some contexts. Recently, the lab has considered intrinsic mechanisms that promote advantage of additional variant genes. Surprisingly, all genes studied so far differ slightly in their potency, the molecular mechanisms that confer fitness, and probably the conditions under which they are most likely to triumph. These mechanisms will be compared and discussed, in addition to the interplay between aging, more broadly, and clonal hematopoiesis.Speakers: Dr. Margaret Goodell

    • 12:06 p.m. "Regulation of hematopoietic stem cells and host immunity by light and darkness cues"12:06 p.m. - 12:30 p.m.Hematopoietic stem and progenitor cells (HSPCs) are primarily maintained in an undifferentiated, and quiescent state in the mouse bone marrow (BM). We have recently found that circadian cues regulate daily murine HSPC fate decisions. Daily light and darkness cues induce a fraction of BM HSPCs to differentiate and egress from the BM in daylight to replenish the circulation with mature blood and immune cells. While darkness metabolically elevates their self-renewal to maintain the BM reservoir of undifferentiated HSPC. This topic and regulation of host immunity by circadian light and darkness onset will be discussed.Speakers: Prof. Tsvee Lapidot




X
X