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Lingbo Zhang

Lingbo Zhang

Assistant Professor
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

The research in the Zhang laboratory centers on normal and malignant stem and progenitor cells in the hematopoietic system and decodes the role of metabolites, including micronutrients and neurotransmitters, in the tumor microenvironment and their genetic effectors in regulating hematologic malignancies. The ultimate goal is to understand how environmental signals such as diets and nervous system activities modulate development and cancers.

Our research focuses on decoding the role of metabolites, including micronutrients and neurotransmitters, in the tumor microenvironment of hematologic malignancies. We utilize a combination of CRISPR/Cas functional genomics and metabolomics approaches to systematically uncover key metabolites and their genetic effectors, including receptors and metabolic enzymes, to reveal mechanistic insights of and identify key drug targets for hematologic malignancies.

Together, the Zhang laboratory recently uncovered a series of critical metabolites in the tumor microenvironment, including acetylcholine and pyridoxal, and their genetic effectors as novel regulators of hematologic malignancies. We 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. We also identified vitamin B6 pathway as a nutritional and metabolic dependency in acute myeloid leukemia (AML) that coordinates nucleotides and putrescine metabolism 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 are building pharmacological approaches to target these novel regulators, and our findings will help to treat devastating hematologic malignancies, including refractory anemia, myelodysplasia and leukemia.

DoD Bone Marrow Failure Research Program Idea Development Award

NIH Research Evaluation and Commercialization Hub Proof of Concept Award

Edward P. Evans Foundation EvansMDS Young Investigator Award

NIH Research Evaluation and Commercialization Hub Feasibility Award

Chinese Government Award for Outstanding Self-finance Students Abroad

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

See all Zhang news

Selected Publications

Targeting low-risk myelodysplastic syndrome with novel therapeutic strategies

Jul 2021 | Trends in Molecular Medicine
Trivedi, Gaurang, Inoue, Daichi, Zhang, Lingbo

Vitamin B6 Addiction in Acute Myeloid Leukemia

13 Jan 2020 | Cancer Cell | 37(1):71-84
Chen, C, Li, B, Millman, S, Chen, C, Li, X, Morris, J, Mayle, A, Ho, Y, Loizou, E, Liu, H, Qin, W, Shah, H, Violante, S, Cross, J, Lowe, S, Zhang, L

Muscarinic acetylcholine receptor regulates self-renewal of early erythroid progenitors

2019 | Science Translational Medicine | 11(511)
Trivedi, Gaurang, Inoue, Daichi, Chen, Cynthia, Bitner, Lillian, Chung, Young, Taylor, Justin, Gönen, Mithat, Wess, Jürgen, Abdel-Wahab, Omar, Zhang, Lingbo

ZFP36L2 is required for self-renewal of early burst-forming unit erythroid progenitors

4 Jul 2013 | Nature | 499(7456):92-6
Zhang, L, Prak, L, Rayon-Estrada, V, Thiru, P, Flygare, J, Lim, B, Lodish, H

From stem cell to red cell: regulation of erythropoiesis at multiple levels by multiple proteins, RNAs, and chromatin modifications

8 Dec 2011 | Blood | 118(24):6258-68
Hattangadi, S, Wong, P, Zhang, L, Flygare, J, Lodish, H

All Publications

MicroRNAs in erythroid and megakaryocytic differentiation and megakaryocyte-erythroid progenitor lineage commitment

Nov 2012 | Leukemia | 26(11):2310-6
Zhang, L, Sankaran, V, Lodish, H

miR-191 regulates mouse erythroblast enucleation by down-regulating Riok3 and Mxi1

15 Jan 2011 | Genes and Development | 25(2):119-24
Zhang, L, Flygare, J, Wong, P, Lim, B, Lodish, H

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