Tsvee Lapidot

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.