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Lingbo Zhang

Lingbo Zhang

CSHL Fellow

Ph.D., Joint program of Massachusetts Institute of Technology and National University of Singapore, 2013

lbzhang@cshl.edu | (516) 367-5414 (p)

The research of my lab focuses on normal and malignant hematopoietic stem and progenitor cells, specifically early erythroid progenitors and leukemic cells. We utilize both CRISPR/Cas functional genomic and forward chemical genomic approaches to uncover critical genes and small chemical compounds regulating the self-renewal of normal and malignant hematopoietic stem and progenitor cells. The ultimate goal of our research is to identify novel therapeutics for treatment-resistant hematopoietic malignancies including myelodysplastic syndrome and acute leukemia through targeting of novel self-renewal pathways and metabolic vulnerabilities.

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.

2016 NIH Research Evaluation and Commercialization Hub (REACH) Award
2018 EvansMDS Young Investigator Award
2018 NIH Research Evaluation and Commercialization Hub Award (Proof of Concept Award)

Zhang, L. and Prak, L. and Rayon-Estrada, V. and Thiru, P. and Flygare, J. and Lim, B. and Lodish, H. F. (2013) ZFP36L2 is required for self-renewal of early burst-forming unit erythroid progenitors. Nature, 499(7456) pp. 92-6.

Zhang, L. and Sankaran, V. G. and Lodish, H. F. (2012) MicroRNAs in erythroid and megakaryocytic differentiation and megakaryocyte-erythroid progenitor lineage commitment. Leukemia, 26(11) pp. 2310-6.

Hattangadi, S. M. and Wong, P. and Zhang, L. and Flygare, J. and Lodish, H. F. (2011) From stem cell to red cell: regulation of erythropoiesis at multiple levels by multiple proteins, RNAs, and chromatin modifications. Blood, 118(24) pp. 6258-68.

Zhang, L. and Flygare, J. and Wong, P. and Lim, B. and Lodish, H. F. (2011) miR-191 regulates mouse erythroblast enucleation by down-regulating Riok3 and Mxi1. Genes Dev, 25(2) pp. 119-24.

Additional materials of the author at
CSHL Institutional Repository