Ming-Ming Zhou, PhD
img_Ming-Ming Zhou
PROFESSOR & CHAIR | Pharmacological Sciences
PROFESSOR | Oncological Sciences
CO-DIRECTOR, DRUG DISCOVERY INSTITUTE
Research Topics
Alzheimer's Disease, Biochemistry, Biophysics, Cancer, Chromatin, Drug Design and Discovery, Epigenetics, Gene Regulation, Inflammation, Structural Biology, T Cells, Transcription Factors
Multi-Disciplinary Training Area
Cancer Biology [CAB], Disease Mechanisms and Therapeutics (DMT)
Transcription Mechanism and Drug Discovery

The Zhou Laboratory focuses on unraveling the basic molecular mechanisms of chromatin-mediated gene transcription, essential for defining cell types and implicated in diseases. Dr. Zhou and colleagues study the structure-function and regulatory mechanisms of histone modifying enzymes (writers and erasers) and histone readers in gene transcription. Using a structural mechanism-guided strategy, they design chemical compounds to selectively modulate cell-type specific gene transcription. Notable contributions include the seminal discovery of the bromodomain as the first histone reader for acetyl-lysine recognition (Dhalluin et al., 1999) and revealing how gene regulatory proteins utilize combinatorial binding of modified histones to direct transcription (Zeng et al., 2010). Recent research provided unequivocal evidence for the influential ‘histone code’ hypothesis, illustrating how specific chemical modifications of a single histone residue (H3K27) dictate distinct gene transcription outcomes (Liu et al., 2023). Dr. Zhou’s pioneering work on chemical modulation of bromodomain/acetyl-lysine binding for disease treatment (Zeng et al., 2005) opened the field of bromodomain drug discovery pursued by the pharmaceutical industry.

 

Selected Publications

Dhalluin, C., Carlson, J., Zeng, L., He, C., Aggarwal, A.K., & Zhou, M.-M. (1999) Structure and Ligand of a Histone Acetyltransferase Bromodomain. Nature 399(6735): 491-496.

Zeng, L., Li, J., Muller, M., Yan, S., Mujtaba, S., Pan, C., Wang, Z., & Zhou, M.-M. (2005) Selective Small Molecules Blocking HIV-1 Tat and Coactivator PCAF Association. Journal of Am. Chem. Soc. 127(8): 2376-2377.

Zeng, L., Zhang, Q., Li, S.D., Plotnikov, A.N., Walsh, M.J., & Zhou, M.-M. (2010) Mechanism and Regulation of Acetylated Histone Binding of the Tandem PHD Finger of DPF3b. Nature 466(7303): 258-62.

Yap, K.L., Li, S., Munoz-Cabello, A.M., Raguz, S., Zeng, L., Mujtaba, S., Gil, J., Walsh, W.J., & Zhou, M.-M. (2010) Molecular Interplay of the Non-coding RNA ANRIL and Methylated Histone H3 Lysine 27 by Polycomb CBX7 in Transcriptional Silencing of INK4a. Molecular Cell 38(5): 662-674.

Shi, J., Wang, Y., Zeng, L., Wu, Y., Deng, J., Zhang, Q., Dong, C., Li, J., Rusinova, E., Zhang, G., Wang, C., Zhu, H., Evers, B.M., Zhou, M.-M., & Zhou, B.P. (2014) Disrupting the Interaction of BRD4 with Diacetylated Twist Suppresses Tumorigenesis in Basal-like Breast Cancer. Cancer Cell 25(2): 210-225.

Yu, D., Liang, Y., Kim, C., Jaganathan, A., Ji, D., Han, X., Yang, X., Jia, Y., Gu, R., Wang, C., Zhang, Q., Cheung, K.L., Zhou, M.-M., & Zeng, L. (2023) Structural Mechanism of BRD4-NUT and p300 Bipartite Interactions in Propagating Aberrant Gene Transcription in Chromatin in NUT Carcinoma. Nature Commun. 14(1): 378.

Liu, N., Konuma, K., Sharma, R., Wang, D., Zhao, N., Cao, L.L., Ju, Y., Liu, D., Wang, Shui, Bosch, A., Sun, Y.F., Zhang, S., Ji, D.L., Nagatoishi, S., Suzuki, N., Kikuchi, M., Wakamori, M., Zhao, C.C., Ren, C.Y., Zhou, T.J.C., Xu. Y.Y., Meslamani, J., Fu, S.B., Umehara, T., Tsumoto, K., Akashi, S., Zeng, L., Roeder, R.G., Walsh, M.J., Zhang, Q., & Zhou, M.-M. (2023) Histone H3 Lysine 27 Crotonylation Mediates Gene Transcriptional Repression in Chromatin. Molecular Cell 83(13): 2206-2221.


PhD, Purdue University

Postdoctoral Fellow, Abbott Laboratories

2021

Fellow, the National Adademy of Inventors (NAI)

2019

The Jacobi Medallion, the Mount Sinai Health System

2012

Fellow, the American Association of the Advancement of Science (AAAS)

2003

GlaxoSmithKline Drug Discovery and Development Award

1999

American Cancer Society Young Investigator Award

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device, biotechnology companies, and other outside entities to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their outside financial relationships.

Below are financial relationships with industry reported by Dr. Zhou during 2023 and/or 2024. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Board Service

  • Parkside Scientific Inc.
  • New York Structural Biology Center

Consulting or Other Professional Services Examples include, but are not limited to, committee participation, data safety monitoring board (DSMB) membership

  • Parkside Scientific Inc.

Equity (Stock or stock options valued at greater than 5% ownership of a publicly traded company or equity of any value in a privately held company)

  • Parkside Scientific Inc.

Founder/Co-Founder/Partner

  • Parkside Scientific Inc.

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website. Patients may wish to ask their physician about the activities they perform for companies.