Stem cell regulation via dynamic interactions of the
nervous and immune systems with the microenvironment
 |
Prof. Tsvee Lapidot Office: Wolfson Building, Room 301 |
| Hematopoietic stem cells are a rare population within the bone marrow, which actively maintain continuous production of all mature blood cells, including the immune system. Our major goals are to decipher molecular mechanisms that govern stem cell development, proliferation, differentiation and migration in steady state homeostasis, stress induced recruitment and clinical mobilization. We seek to determine the mutual cross-talk between hematopoietic stem cells, their microenvironment, including the nervous and immune systems, which altogether, we refer to as the “brain-bone-blood triad”. We focus on bone remodeling and niche regulation of stem cell maintenance, retention, proliferation and recruitment to the circulation as part of host defense and repair mechanism. The unique roles of stromal cells, chemokines, cytokines, adhesion molecules, and proteolytic enzymes, which regulate both normal and leukemic human stem cells, are currently investigated. These include signaling events mediated by the chemokine SDF-1 and its major receptor CXCR4, neurotransmitters and myeloid cytokines, functional preclinical homing, repopulation and mobilization models for normal and leukemic human stem cells, in transplanted immune deficient mice as well as complementary in vitro migration and colony assays. | |