Zhou's research is directed at better understanding the biology of epigenetic control of gene transcription of the 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, differentiation, and re-programming to human cancer and inflammation, as well as neurodegenerative disorders. Among his major contributions to science are the Zhou Lab's discovery of the bromodomain as the acetyl-lysine binding domain ('chromatin reader') in gene transcription (Nature 1999)[7] and the first demonstrations 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] and long non-coding RNA in the 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]
^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. PMID15724976.
^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. PMID25549891. S2CID10192177.
^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. PMID15724976.
