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My graduate and postgraduate work focused on normal hematopoietic stem cell (HSCs) functions. Using models of murine and human hematopoiesis, my research focused on fundamental processes that define HSCs such as migration, self-renewal and differentiation. Late in my postgraduate work, I focused on complex interactions between bone marrow microenvironment and HSCs. These efforts contributed to our understanding of how bone marrow microenvironment communicates with HSCs via gap junctions and thus, cytoplasmic to cytoplasmic communications. In this regard, the microenvironment serves as a scavenger of reactive oxygen species and protects HSCs. More so, we have revealed that the bone marrow stroma protects human HSCs from the pro-differentiation effects of vitamin A. Our findings, suggest that HSCs are intrinsically programmed to undergo differentiation, form blood and thus, rapidly disappear. The microenvironment appears poised to prevent rapid HSC differentiation and maintain them for the lifetime of the individual.
Most recently, my laboratory has found that the stem cell niche via expression of drug metabolizing enzymes creates a virtually drug free “sanctuary” where malignant HSCs are protected from systemic chemotherapy. By understanding how various niches in the bone marrow contribute to such resistance, my laboratory together with clinical translational colleagues at Johns Hopkins and elsewhere are now developing and testing clinical tools that target the bone marrow microenvironment to improve outcomes in hematological malignancies. While our work in this area continues, we are now well situated to expand our finding beyond the realm of hematological malignancies and into oncology in general.