Ming-Ming Zhou

Ming-Ming Zhou is an American scientist who focuses on structural and chemical biology, NMR spectroscopy, and drug design. He is the Dr. Harold, Golden Lamport Professor, and Chairman of the Department of Pharmacological Sciences.[1] He is also the co-director of the Drug Discovery Institute at the Icahn School of Medicine at Mount Sinai and Mount Sinai Health System in New York City, as well as Professor of Sciences.[2]

Ming-Ming Zhou
BornNovember, 1962
East China
NationalityChinese
Alma materEast China University of Science and Technology
Michigan Technological University
Purdue University
Scientific career
FieldsStructural and Chemical Biology
Epigenetics
Drug Discovery
InstitutionsIcahn School of Medicine at Mount Sinai
Mount Sinai Medical Center

Zhou has published more than 180 research articles and is an inventor of 28 patents. His research has been funded by grants from federal, state and private research foundations including: the National Institutes of Health, the National Science Foundation, the New York State Stem Cell Science, the Institute for the Study of Aging, the American Foundation for AIDS Research, the American Cancer Society, GlaxoSmithKline, the Michael J. Fox Foundation, the Samuel Waxman Cancer Research Foundation,[3] and the Wellcome Trust. He serves on the board of directors at the New York Structural Biology Center, as well as on the editorial boards of ACS Medicinal Chemistry Letters, the Journal of Molecular Cell Biology[4] and Cancer Research.[5] Zhou received the GlaxoSmithKline Drug Discovery Research Award in 2003 for his work in anti-HIV/AIDS therapy development, and the Jacobi Medallion in 2019.[6] He is also an elected fellow of the American Association for the Advancement of Science (2012).

Biography

Zhou earned his B.E. in chemical engineering from the East China University of Science and Technology (Shanghai, PRC) in 1984. He earned his M.S. in chemistry from the Michigan Technological University in 1988 and a Ph.D. in chemistry from Purdue University in Indiana in 1993. He completed his postdoctoral fellowship at Abbott Laboratories in Chicago, Illinois, then joined the faculty of the Mount Sinai Medical School in 1997.

Zhou's research is directed at better understanding of the biology of epigenetic control of gene transcription of human genome to attain both the underlying basic principles and rational design of novel chemical compounds that modulate gene expression in chromatin. His research studies have broad implications in human biology and disease, ranging from cell development, to stem cell self-renewal and differentiation, and re-programming to human cancer and inflammation, as well as neurodegenerative disorders. Among his major contributions to science is the Zhou Lab's seminal discovery of the bromodomain as the acetyl-lysine binding domain ('chromatin reader') in gene transcription (Nature 1999),[7] and their first demonstration of druggability and therapeutic potential of bromodomain proteins in gene transcription to treat a wide array of human diseases including cancer and inflammation.[8] This concept has had transformative impacts in epigenetic drug discoveries in the pharmaceutical industry.[9][10]

The Zhou Lab further discovered the tandem PHD finger of DPF3b as a first alternative to the bromodomain for acetyl-lysine binding (Nature 2010),[11] and the PAZ domain as the RNA binding domain in RNAi (Nature 2003).[12] His work also addresses the role of histone lysine methylation (Nature Cell Biol. 2008)[13] as well as long non-coding RNA in epigenetic control of gene transcription in human stem cell maintenance and differentiation (Mol. Cell 2010).[14]

Zhou's work in rational design of chemical probes for mechanism-driven research led to the discovery of the HIV Tat/human co-activator PCAF interaction as a potential novel anti-HIV therapy target.[15] His group has developed chemical probes that modulate the transcriptional activity of human tumor suppressor p53 under stress conditions. His recent work includes the development of a novel gene transcriptional silencing technology.[16] Additional research discoveries include structural mechanisms as well as drug target discovery and validation for human cancers, particularly triple-negative breast cancer (TNBC),[17][18] and inflammatory disorders such as inflammatory bowel disease (IBD)[19][20] and multiple sclerosis.[21]

Current and past society memberships include The Harvey Society, the Biophysical Society,[22] the American Chemical Society, the American Society for Biochemistry and Molecular Biology, the American Association for the Advancement of Science and the New York Academy of Sciences. He serves on multiple editorial boards and reviews grants for the American Cancer Society, the American Heart Association, the National Institutes of Health and the National Science Foundation.

Awards and honors
  • 2003 GlaxoSmithKlineDrug Discovery and Development Award[23]
  • 2009 Elected Member, The Academy of Sciences & Arts at Michigan Technological University[24]
  • 2019 The Jacobi Medallion,[25] The Mount Sinai Health System

Patents
“Methods of Identifying Modulators of the FGF Receptors” US 7,108,984 B2
“ZA Loops of Bromodomains” US 7,589,167 B2
"Method of Suppressing Gene Transcription Through Histone Lysine Methylation" US 9,249,190 B2; US 10,280,408 B2
"Cyclic Vinylogous Amides as Bromodomain Inhibitors" US 9,884,806 B2; US 10,351,511 B2
"Methods of Modulating Bromodomains" US 2004/0009613 A1

References
  1. "Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai".
  2. "Mount Sinai School of Medicine - Ming-Ming Zhou". Retrieved March 8, 2011.
  3. "The Samuel Waxman Cancer Research Foundation".
  4. "Journal of Molecular Cell Biology - Editorial Board". Archived from the original on July 27, 2011. Retrieved March 8, 2011.
  5. "Cancer Research: Editorial Board". Retrieved March 8, 2011.
  6. "Zhou Jacobi Video on Youtube".
  7. Dhalluin C, Carlson JE, Zeng L, He C, Aggarwal AK, Zhou MM (June 1999). "Structure and ligand of a histone acetyltransferase bromodomain". Nature. 399 (6735): 491–6. Bibcode:1999Natur.399..491D. doi:10.1038/20974. PMID 10365964. S2CID 1210925.
  8. Zeng L, Li J, Muller M, Yan S, Mujtaba S, Pan C, Wang, Z, Zhou, MM (2005). "Selective Small Molecules Blocking HIV-1 Tat and Coactivator PCAF Association". Journal of the American Chemical Society. 127 (8): 2376–7. doi:10.1021/ja044885g. PMID 15724976.
  9. Verdin E, Melanie O (April 2015). "50 Years of Protein Acetylation: From Gene Regulation to Epigenetics, metabolism and Beyond". Nature Reviews Molecular Cell Biology. 16 (4): 258–64. doi:10.1038/nrm3931. PMID 25549891. S2CID 10192177.
  10. Zaware, N, Zhou, MM (2019). "Bromodomain Biology and Drug Discovery". Nature Structural & Molecular Biology. 26 (10): 870–9. doi:10.1038/s41594-019-0309-8. PMC 6984398. PMID 31582847.
  11. Zeng L, Zhang Q, Li S, Plotnikov AN, Walsh MJ, Zhou MM (July 2010). "Mechanism and regulation of acetylated histone binding by the tandem PHD finger of DPF3b". Nature. 466 (7303): 258–62. Bibcode:2010Natur.466..258Z. doi:10.1038/nature09139. PMC 2901902. PMID 20613843.
  12. Yan KS, Yan S, Farooq A, Han A, Zeng L, Zhou MM (November 2003). "Structure and conserved RNA binding of the PAZ domain". Nature. 426 (6965): 468–74. Bibcode:2003Natur.426..468Y. doi:10.1038/nature02129. PMID 14615802. S2CID 52874237.
  13. Mujtaba S, Manzur KL, Gurnon JR, Kang M, Van Etten JL, Zhou MM (August 2008). "Epigenetic transcriptional repression of cellular genes by a viral SET protein". Nature Cell Biology. 10 (9): 1114–1122. doi:10.1038/ncb1772. PMC 2898185. PMID 19160493.
  14. Yap KL, Li S, Muñoz-Cabello AM, Raguz S, Zeng L, Mujtaba S, Gil J, Walsh MJ, Zhou MM (June 2010). "Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a". Molecular Cell. 38 (5): 662–74. doi:10.1016/j.molcel.2010.03.021. PMC 2886305. PMID 20541999.
  15. Zeng L, Li J, Muller M, Yan S, Mujtaba S, Pan C, Wang Z, Zhou MM (March 2005). "Selective small molecules blocking HIV-1 Tat and coactivator PCAF association". Journal of the American Chemical Society. 127 (8): 2376–7. doi:10.1021/ja044885g. PMID 15724976.
  16. "Mount Sinai researchers discover technology that silences genes". Retrieved March 8, 2011.
  17. 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 BM, Zhou MM, Zhou BP (Feb 2014). "Disrupting the Interaction of BRD4 with Diacetylated Twist Suppresses Tumorigenesis in Basal-like Breast Cancer". Cancer Cell. 25 (2): 210–25. doi:10.1016/j.ccr.2014.01.028. PMC 4004960. PMID 24525235.
  18. Stratikopoulos EE, Dendy M, Szabolcs M, Khaykin AJ, Lefebvre C, Zhou MM, Parsons R (2015). "Kinase and BET Inhibitors Together Clamp Inhibition of PI3K Signaling and Overcome Resistance to Therapy". Cancer Cell. 27 (6): 837–851. doi:10.1016/j.ccell.2015.05.006. PMC 4918409. PMID 26058079.
  19. Cheung KL, Zhang F, Jaganathan A, Sharma R, Zhang Q, Konuma T, Shen T, Lee JY, Ren CY, Chen CH, Lu G, Olson MR, Zhang W, Kaplan MH, Littman DR, Walsh MJ, Xiong H, Zeng L, Zhou MM (March 2017). "Distinct Roles of Brd2 and Brd4 in Potentiating the Transcriptional Program for Th17 Cell Differentiation". Molecular Cell. 65 (6): 1068–80. doi:10.1016/j.molcel.2016.12.022. PMC 5357147. PMID 28262505.
  20. Cheung KL, Lu GM, Sharma R, Vincek AS, Zhang RH, Plotnikov AN, Zhang F, Zhang Q, Ju Y, Hu Y, Zhao L, Han X, Meslamani J, Xu F, Jaganathan A, Shen T, Zhu H, Rusinova E, Zeng L, Zhou JC, Yang JC, Peng L, Ohlmeyer M, Walsh MJ, Zhang DY, Xiong HB, Zhou MM (March 2017). "Selective BET Bromodomain Inhibition Blocks Th17 Cell Differentiation and Ameliorates Colitis in Mice". Proceedings of the National Academy of Sciences of the United States of America. 114 (11): 2952–7. doi:10.1073/pnas.1615601114. PMC 5358349. PMID 28265070.
  21. Gacias-Monserrat M, Gerona-Navarro G, Plotnikov AN, Zhang GT, Zeng L, Kaur J, Moy G, Rusinova E, Rodríguez-Fernández Y, Matikainen B, Joshua J, Vincek A, Joshua J, Casaccia P, Zhou MM (July 2014). "Selective Chemical Modification of Gene Transcription Favors Oligodendrocyte Lineage Progression". Chemistry & Biology. 21 (7): 841–54. doi:10.1016/j.chembiol.2014.05.009. PMC 4104156. PMID 24954007.
  22. "Biophysical Society". Retrieved March 8, 2011.
  23. "GlaxoSmithKline Drug Discovery and Development Research Grant Program 2003". Retrieved March 8, 2011.
  24. "Michigan Technological University - College of Sciences and Arts". Retrieved March 8, 2011.
  25. "Zhou Jacobi Video on Youtube".
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