Lingbo Zhang

Stem and progenitor cells of many adult lineages undergo self-renewal. Exploiting self-renewal mechanisms holds great promise for the development of regenerative medical strategies and for the prevention of abnormal cell proliferation in cancer. Our research centers on normal and malignant stem and progenitor cells in the hematopoietic system. Thus far, we have utilized CRISPR/Cas functional genomics to uncover novel regulators of self-renewal of early erythroid progenitor, the insufficiency of which contributes to refractoriness of myelodysplastic syndrome to current therapies. Through collaborations with medicinal chemists, we have built pharmacological approaches to target these regulators, and these findings will help treat refractory myelodysplastic syndrome and a broad spectrum of anemias of cancer chemotherapy and radiation therapy. Our newfound knowledge of self-renewal in normal cells also helped us to understand the uniqueness of malignant cells. As an effort to identify mechanistic divergence between normal and malignant hematopoietic stem and progenitor cells, we seek to selectively inhibit self-renewal and its related metabolic processes in leukemic cells as novel therapeutic strategies for leukemia.