Lingbo Zhang

Stem and progenitor cells of many adult lineages undergo self-renewal. Exploiting self-renewal mechanisms holds great promise for the development of cell-based and regenerative medical strategies and for prevention of the abnormal activation of self-renewal pathways that contribute to irregular cell proliferation and carcinogenesis. Our research centers on normal and malignant stem and progenitor cells in the blood-forming system, specifically early erythroid progenitors and leukemic cells. Thus far, we have utilized reverse genetics to uncover several critical genes regulating early erythroid progenitor self-renewal, a first step towards our understanding of this process. To expand the therapeutic impact of this work, we aim to comprehensively dissect self-renewal pathways to pinpoint potential drug targets, as well as employ high-throughput screening approaches to identify molecules and chemical compounds capable of triggering self-renewal and expansion of these progenitors. These findings will help treat a broad spectrum of treatment-resistant anemias of myelodysplastic syndrome and cancer chemotherapy and radiation therapy. Our newfound knowledge of self-renewal in normal cells can also be applied to research of leukemic cells, a population of malignant cells whose self-renewal machinery has been hijacked. By identifying the mechanistic divergence between normal and malignant hematopoietic progenitors and stem cells, we seek to selectively inhibit self-renewal in leukemic cells as novel therapies for leukemias.