Lingbo Zhang

Stem and progenitor cells of many adult lineages undergo self-renewal and differentiation, and environmental signals are critical regulators of this process. Exploiting mechanisms especially the role of nervous system activity and nutrient as well as related immunomodulatory effect holds great promise for the development of regenerative medical strategies and the prevention of abnormal cell proliferation in cancer. The research of my laboratory centers on normal and malignant stem and progenitor cells in the hematopoietic system. We utilize functional genomics including chemical and CRISPR/Cas9 genetic approaches to uncover nervous system activity and nutrient as well as related immunomodulatory effect in regulating this process.

My laboratory recently identified cholinergic receptor muscarinic 4 – CHRM4 as a novel regulator of early erythroid progenitor self-renewal and a therapeutic target for myelodysplastic syndrome (MDS). Our research uncovered the Hematopoietic Arc – HematopoArc as a novel nervous system activity based regulatory mechanism of hematopoietic stem and progenitor cell self-renewal and differentiation, which is a missing information without which we cannot target a group of devastating hematologic diseases. We also identified vitamin B6 pathway as a nutritional and metabolic dependency in acute myeloid leukemia (AML) through coordinating multiple metabolic events specifically required for leukemia maintenance. Our research uncovered vitamin B6 pathway as a pharmacologically -actionable target to treat leukemia with minimal bone marrow suppression effect. Through collaborations with medicinal chemists, we build pharmacological approaches to target these novel regulators, and our findings will help to treat devastating hematologic diseases and malignancies, including anemia, myelodysplastic syndrome and leukemia.