Lingbo Zhang

Lingbo Zhang

CSHL Fellow
Cancer Center Member

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

lbzhang@cshl.edu | 516-367-5414

Faculty Profile

Proper balancing of self-renewal and differentiation in hematopoietic stem and progenitor cells is the central question in hematopoiesis. My laboratory investigates how environmental signals including nervous system activity and nutrient as well as related immunomodulatory effect regulate this key process and aims to develop novel therapeutic strategies for hematologic diseases and malignancies.

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.

2018 NIH Research Evaluation and Commercialization Hub Proof of Concept Award
2018 Edward P. Evans Foundation EvansMDS Young Investigator Award
2016 NIH Research Evaluation and Commercialization Hub Feasibility Award
2013 Chinese Government Award for Outstanding Self-finance Students Abroad
2008 Tsinghua University Outstanding Master Degree Thesis Award

Nature Chemical Biology – Hooked on vitamins

World Pharma News – Vitamin B6, leukemia’s deadly addiction

Medical News Today – Leukemia’s unexpected link to vitamin B-6

Genetic Engineering & Biotechnology News – Leukemia’s Favorite Fix, Vitamin B6, Vulnerable to Pharmacological Blockade

Drug Target Review – A novel target revealed for myelodysplastic syndrome

BioSpace – Newly discovered target overcomes drug resistance in lethal blood cancer

Bioengineer – Discovery could improve MDS cancer treatment

LI Bioscience Hub Backs 10 In New Funding Round

Scientists identify potential drug target for treatment-resistant anemias

Nature Reviews Genetics – Regulating Self-renewal

Science – Editor’s Choice – Enucleation Regulation

Trivedi, Gaurang and Inoue, Daichi and Zhang, Lingbo (2021) Targeting low-risk myelodysplastic syndrome with novel therapeutic strategies. Trends in Molecular Medicine,

Chen, C. C. and Li, B. and Millman, S. E. and Chen, C. and Li, X. and Morris, J. P. Iv and Mayle, A. and Ho, Y. J. and Loizou, E. and Liu, H. and Qin, W. and Shah, H. and Violante, S. and Cross, J. R. and Lowe, S. W. and Zhang, L. (2020) Vitamin B6 Addiction in Acute Myeloid Leukemia. Cancer Cell, 37(1) pp. 71-84.

Trivedi, Gaurang and Inoue, Daichi and Chen, Cynthia and Bitner, Lillian and Chung, Young Rock and Taylor, Justin and Gönen, Mithat and Wess, Jürgen and Abdel-Wahab, Omar and Zhang, Lingbo (2019) Muscarinic acetylcholine receptor regulates self-renewal of early erythroid progenitors. Science Translational Medicine, 11(511)

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.

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.

Additional materials of the author at
CSHL Institutional Repository