Ming-Ming Zhou

Ming-Ming Zhou, Ph.D., is an internationally recognized expert in structural and chemical biology, NMR spectroscopy of protein structure-function and rational small-molecule design.[1] He is currently the Dr. Harold and Golden Lamport Professor and Chairman of the Department of Pharmacological Sciences and Co-Director of the Experimental Therapeutics Institute at the Mount Sinai School of Medicine and Mount Sinai Medical Center in New York City as well as Professor of Oncological Sciences.[2]

Ming-Ming Zhou, Ph.D.
Alma mater	East China University of Science and Technology Michigan Technological University Purdue University
Scientific career
Fields	structural and chemical biology
Institutions	Mount Sinai Medical Center

Zhou has published more than 110 peer-reviewed research articles and has received multiple 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, and the Wellcome Trust. He serves on the editorial boards of ACS Medicinal Chemistry Letters, the Journal of Molecular Cell Biology[3] and Cancer Research.[4] He has been awarded five patents.

Biography

Zhou earned his B.S. 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 Mount Sinai Medical Center in 1997.

Zhou’s research is directed at understanding the fundamental molecular mechanisms that govern cellular signal transduction and epigenetic control of gene transcription in human biology of health and disease by using combined structural/chemical biology and molecular/cell biology approaches. He received the GlaxoSmithKline Drug Discovery Research Award in 2003 for his work in novel anti-HIV/AIDS therapy development. His research contributions include the discovery of the bromodomain as the acetyl-lysine binding domain in epigenetic gene regulation,[5] the tandem PHD finger of DPF3b as a first alternative to the bromodomain for acetyl-lysine binding,[6] and the PAZ domain as the RNA binding domain in RNAi.[7] His recent work also addresses the role of histone lysine methylation (Nature Cell Biol. 2008)[8] as well as long non-coding RNA in epigenetic control of gene transcription in human stem cell maintenance and differentiation.[9]

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.[10] His group has also 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.

The current focuses of his laboratory include the roles of the trithorax protein complexes and the polycomb repressive complexes in gene activation and silencing in human biology of health and disease such as stem cell self-renewal and lineage commitment, cancer and inflammation.[11] Additional research interests include the structure and mechanisms of epigenetic gene regulation and chromatin biology, structure-based small molecule design, mechanism-based disease biology and drug discovery in HIV/AIDS, human cancer, leukemia and inflammation, neurodegenerative disorders including multiple sclerosis, Parkinson's disease, and Alzheimer's disease.

Current and past society memberships include The Harvey Society, the Biophysical Society,[12] 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

• 2009 Elected to the Academy of Sciences & Arts at Michigan Technological University[13]
• 2006 Dr. Harold and Golden Lamport Professorship in Physiology and Biophysics
• 2003 GlaxoSmithKlineDrug Discovery and Development Award[14]
• 1999 American Cancer Society Young Investigator Award

Patents

Title	Number
“Methods of Identifying Modulators of the FGF Receptors”	20060019296[15]
“Methods of Identifying Modulators of Bromodomains”	7,589,167[16]
“Methods and Compositions for the Treatment of Disorders of HIV Infection”	USSN10/413,785 pending
“Small-Molecular Chemicals That Inhibit HIV Tat Interactions with Human PCAF in Viral Transcriptional Activation”	US Provisional PA, pending.
“Method of Suppressing Gene Transcription Through Histone Lysine Methylation”	US Provisional PA Serial No. 61/041,363, pending

Publications

Partial list:

• Zeng L.; Zhang Q.; Li SiDe; Plotnikov A.N.; Walsh M.J.; Zhou M.-M. (2010). "Mechanism of Multivalent Histone Interactions with Human DPF3b in Gene Transcription". Nature. 466 (7303): 258–262. doi:10.1038/nature09139. PMC 2901902. PMID 20613843.
• Yap K.L.; Li S.; Munoz-Cabello A.M.; Raguz S.; Zeng L.; Mujtaba S.; Gil J.; Walsh W.J.; Zhou M.-M.; et al. (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. doi:10.1016/j.molcel.2010.03.021. PMC 2886305. PMID 20541999.
• Wei H, Zhou MM (October 2010). "Dimerization of a viral SET protein endows its function". Proc. Natl. Acad. Sci. U.S.A. 107 (43): 18433–8. doi:10.1073/pnas.1009911107. PMC 2972924. PMID 20937900..
• Zhang Q.; Chakravarty S.; Ghersi D.; Plotnikov A.N.; Sanchez R.; Zhou M.-M. (2010). "Biochemical Profiling of Histone Binding Selectivity of the Yeast Bromodomain Family". PLoS ONE. 5 (1): e8903. doi:10.1371/journal.pone.0008903. PMC 2811197. PMID 20126658.
• Barradas M, Anderton E, Acosta JC, et al. (May 2009). "Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS". Genes Dev. 23 (10): 1177–82. doi:10.1101/gad.511109. PMC 2685533. PMID 19451218..
• Mujtaba S.; Manzur K.L.; Gurnon J.R.; Kang M.; Van Etten J.L.; Zhou M.-M. (2008). "Epigenetic Transcription Repression of Cellular Genes by a Viral SET Protein". Nature Cell Biology. 10 (9): 1114–1122. doi:10.1038/ncb1772. PMC 2898185. PMID 19160493.
• Zeng L.; Yao K.L.; Ivanov A.V; Wang X.; Mujtaba S.; Plotnikova O.; Rauscher F.J.; Zhou M.-M. (2008). "Structural Insights into the Functional Cooperativity of the Tandem PHD Finger-Bromodomain of Human KAP1 in Sumoylation-Dependence Gene Silencing". Nature Structural & Molecular Biology. 15 (6): 626–633. doi:10.1038/nsmb.1416. PMC 3331790. PMID 18488044.
• Ivanov A.V.; Peng H.; Yurchenko V.; Yap K.L.; Negorev D.G.; Schultz D.C.; Psulkowsky E.; Fredericks W.J.; White D.E.; et al. (2007). "PHD Domain-Mediated E3 Ligase Activity Directs Intramolecular Sumoylation of an Adjacent Bromodomain which is Required for Gene Silencing". Molecular Cell. 28 (5): 823–37. doi:10.1016/j.molcel.2007.11.012. PMC 4348069. PMID 18082607.
• Pan C.; Mezei M.; Mujtaba S.; Muller M.; Zeng L.; Li J.M.; Wang Z.Y.; Zhou M.-M. (2007). "Structure-Guided Optimization of Small Molecules Selectively Inhibiting Human Immunodeficiency Virus 1 Tat Association with the Human Coactivator p300/CREB Binding Protein-Associated Factor". Journal of Medicinal Chemistry. 50 (10): 2285–2288. doi:10.1021/jm070014g. PMID 17444627.
• Seet B.T.; Dikic I.; Zhou M.-M.; Pawson T (2006). "Reading Protein Modifications with Interaction Domains". Nature Reviews Molecular Cell Biology. 7 (7): 473–483. doi:10.1038/nrm1960. PMID 16829979.
• Qian C.; Zhang Q.; Li S.; Zeng L.; Walsh M.J.; Zhou M.-M. (2005). "Structure and Chromosomal DNA Binding of the SWIRM Domain". Nature Structural & Molecular Biology. 12 (12): 1078–1085. doi:10.1038/nsmb1022. PMID 16299514.
• Sachchidanand Resnick-Silverman; Yan S.; Mutjaba S.; Liu W.-J.; Zeng L.; Manfredi L.; Zhou M-.M. (2005). "Target Structure-Based Discovery of Small Molecules that Block Human p53 and CREB Binding Protein (CBP) Association". Chemistry & Biology. 13: 81–90. doi:10.1016/j.chembiol.2005.10.014. PMID 16426974.
• Zeng L.; Li J.; Muller M.; Yan S.; Mujtaba S.; Pan C.; Wang Z.Y.; Zhou M.-M. (2005). "Selective Small Molecules Blocking HIV-1 Tat and Coactivator PCAF Association". J. Am. Chem. Soc. 127 (8): 2376–2377. doi:10.1021/ja044885g. PMID 15724976.
• Mujtaba M.; He Y.; Zeng L.; Yan S.; Plotnikova O.; Sachchidanand Sanchez; Zeleznik-Le N.; Ronai Z.; Zhou M.-M.; et al. (2004). "Structural Mechanism of the Bromodomain of the Coactivator CBP in p53 Transcriptional Activation". Molecular Cell. 13 (2): 251–263. doi:10.1016/S1097-2765(03)00528-8. PMID 14759370.
• Yan K.S.; Yan S.; Farooq A.; Han A.; Zeng L.; Zhou M.-M. (2003). "Structure and Conserved RNA Binding of the PAZ Domain". Nature. 426 (6965): 469–474. doi:10.1038/nature02129. PMID 14615802.
• Mujtaba S, He Y, Zeng L, et al. (March 2002). "Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF bromodomain". Mol. Cell. 9 (3): 575–86. doi:10.1016/S1097-2765(02)00483-5. PMID 11931765..
• Dorr A.; Kiermer V.; Pedal A.; Rackwitz H.-R.; Henklein P.; Schubert U.; Zhou M.-M.; Verdin E.; Ott M.; et al. (2002). "Transcriptional synergy between at and PCAF is dependent on the binding of acetylated Tat to the PCAF bromodomain". EMBO J. 21 (11): 2715–23. doi:10.1093/emboj/21.11.2715. PMC 125383. PMID 12032084.
• Farooq A.; Chaturvedi G.; Mutjaba S.; Plotnikova O.; Zeng L.; Dhalluin C.; Ashton R.; Zhou M.-M. (2001). "Solution Structure of ERK2 Binding Domain of MAPK Phosphatase MKP-3: Structural Insights into MKP-3 Activation by ERK2". Molecular Cell. 7 (2): 387–399. doi:10.1016/S1097-2765(01)00186-1. PMID 11239467.
• Dhalluin C.; Yan K.; Plotnikova O.; Lee K.W.; Zeng L.; Kuti M.; Mutjaba S.; Goldfarb M.P.; Zhou M.-M.; et al. (2000). "Structural Basis of SNT PTB Domain Interactions with Distinct Neurotrophic Receptors". Molecular Cell. 6 (4): 921–29. doi:10.1016/S1097-2765(05)00087-0. PMC 5155437. PMID 11090629.
• 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. doi:10.1038/20974. PMID 10365964.
• Zhou M.-M.; Huang B.; Olejniczak E.T.; Meadows R.P.; Shuker S.B.; Miyazak M.; Trub T.; Shoelson S.E.; Fesik S.W.; et al. (1996). "Structural Basis of IL-4 Receptor Phosphopeptide Recognition by the IRS-1 PTB Domain". Nature Structural & Molecular Biology. 3 (4): 388–393. doi:10.1038/nsb0496-388. PMID 8599766.
• Zhou M.-M.; Meadows R.P.; Logan T.M.; Yoon H.P.; Wade W.; Ravichandran K.S.; Burakoff S.J.; Fesik S.W. (1995). "Solution Structure of the Shc SH2 domain Complexed with a Tyrosine phosphorylated Peptide from the T-cell Receptor". Proc. Natl. Acad. Sci. U.S.A. 92 (17): 7784–88. doi:10.1073/pnas.92.17.7784. PMC 41230. PMID 7544002.
• Zhou M.-M.; Ravichandran K.S.; Olejniczak E.T.; Petros A.P.; Meadows R.P.; Sattler M.; Harlan J.E.; Wade W.; Burakoff S.J.; et al. (1995). "Structure and Ligand Recognition of the Phosphotyrosine Binding Domain of Shc". Nature. 378 (6557): 584–592. doi:10.1038/378584a0. PMID 8524391.

References

1. "The Michael J. Fox Foundation for Parkinson's Research". Retrieved March 8, 2011.
2. "Mount Sinai School of Medicine - Ming-Ming Zhou". Retrieved March 8, 2011.
3. "Journal of Molecular Cell Biology - Editorial Board". Retrieved March 8, 2011.
4. "Cancer Research: Editorial Board". Retrieved March 8, 2011.
5. 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. doi:10.1038/20974. PMID 10365964.
6. 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. doi:10.1038/nature09139. PMC 2901902. PMID 20613843.
7. 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. doi:10.1038/nature02129. PMID 14615802.
8. 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.
9. 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". Mol. Cell. 38 (5): 662–74. doi:10.1016/j.molcel.2010.03.021. PMC 2886305. PMID 20541999.
10. 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.
11. "Mount Sinai researchers discover technology that silences genes". Retrieved March 8, 2011.
12. "Biophysical Society". Retrieved March 8, 2011.
13. "Michigan Technological University - College of Sciences and Arts". Retrieved March 8, 2011.
14. "GlaxoSmithKline Drug Discovery and Development Research Grant Program 2003". Retrieved March 8, 2011.
15. "Methods of identifying modulators of the FGF receptor - US Patent Application". Archived from the original on October 13, 2012. Retrieved March 8, 2011.
16. "US Patent & Trademark Office". Archived from the original on July 21, 2011. Retrieved March 8, 2011.

External links

• The Mount Sinai Hospital homepage
• The Mount Sinai School of Medicine homepage
• Experimental Therapeutics Institute at the Mount Sinai Medical Center