Gang (Greg) Wang
Assistant Professor of Biochemistry and Biophysics
(PhD - University of California, San Diego)
HONORS & AWARDS
- 2015 The Conquer Cancer Now Award, Concern Foundation for cancer research
- 2014 Janet D. Rowley Medical Research Award, Gabrielle's Angel Foundation for Cancer Research
- 2014 Kimmel Scholar Award, Sidney Kimmel Foundation for Cancer Research
- 2013-2014 American Society of Hematology (ASH) Scholar Award in Basic Science
- 2013 UNC Jefferson-Pilot Fellowships in Academic Medicine Award
- 2011 Martin D. Abeloff, MD V Scholar Award, the V Foundation for Cancer Research
- 2010 NIH/NCI Howard Temin Pathway to Independence Award in Cancer Research
- 2008 Leukemia & Lymphoma Society Fellow Award
- 2007 C.H. Li Memorial Fund Scholar Award, Rockefeller University
With an emphasis on chromatin biology and epigenetics, our group focuses on mechanistic understandings of how chemical modifications of chromatin (see Figure 1) define distinct patterns of mammalian genomes, control gene expression, and regulate cell proliferation versus differentiation during development, and how their deregulations lead to human diseases such as cancer, developmental disorders, and aging. Multiple on-going projects employ modern biological technologies to:
- biochemically isolate and characterize novel factors that specifically bind to covalent post-translational modifications on chromatin (DNA and histones) (see Figure 2 as of a recent study),
- examine the role of epigenetic factors (chromatin-modifying enzymes and chromatin-associated factors) during normal development or in a diseased setting (cancer, see Figure 3) using mouse knockout models;
- analyze epigenomic and transcriptome alternations in normal versus diseased cells utilizing next-generation sequencing technologies (RNA-Seq and ChIP-Seq, see Figure 4),
- identify novel disease-associated genes (leukemia and lymphoma, or hematopoietic stem cell maintenance and aging) using shRNA library-based screening.
The proteins involved in establishing and/or changing the chemical syntax in histones are considered a promising target for drug therapies, so understanding their actions in detail is the next step in developing new treatments for human disease. We are also working closely with UNC Center for Integrative Chemical Biology & Drug Discovery, to develop the small-molecule inhibitors for chromatin-associated factors as novel targeted therapies.
REPRESENTATIVE PUBLICATIONS (click for full publication list)
- Lu R, Wang P, Parton T, Zhou Y, ChrysovergisK, RockowitzS, ChenWY, Abdel-Wahab O, Wade PA, ZhengD, Wang GG. Epigenetic perturbations by Arg882-mutated DNMT3A potentiate aberrant stem cell gene expression program and acute leukemia development. Cancer Cell (in press 2016 July).
- Zhang ZM, Rothbart SB, Allison DF, Cai Q, Harrison JS, Li L, Wang Y, Strahl BD, Wang GG, Song J. An Allosteric Interaction Links USP7 to Deubiquitination and Chromatin Targeting of UHRF1.Cell Rep. 2015 Sep 1;12(9):1400-6. PMID: 26299963
- Xu B, On DM, Ma A, Parton T, Konze KD, Pattenden SG, Allison DF, Cai L, Rockowitz S, Liu S, Liu Y, Li F, Vedadi M, Frye SV, Garcia BA, Zheng D, Jin J, Wang GG. Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia. Blood. 2015 Jan 8; 125(2):346-57. PMCID: PMC4287641.
- Zhou Y, Wang L, Vaseghi HR, Liu Z, Lu R, Alimohamadi S, Yin C, Fu JD, Wang GG, Liu J, Qian L. Bmi1 Is a Key Epigenetic Barrier to Direct Cardiac Reprogramming.Cell Stem Cell. 2016 Mar 3;18(3):382-95. doi: 10.1016/j.stem.2016.02.003. PMID: 26942853
- Wang GG, Konze KD, Tao J. Polycomb genes, miRNA, and their deregulation in B-cell malignancies. Blood. 2015 Feb 19;125(8):1217-1225. PMCID: PMC4335077.
- Xu B, Konze KD, Jin J and Wang GG. Targeting EZH2 and PRC2 dependence as novel anti-cancer therapy. Experimental Hematology. 2015 May 28. pii: S0301-472X(15)00163-0. doi: 10.1016/j.exphem.2015.05.001. [Epub ahead of print]
- Gong H, Qian H, Ertl R, Astle CM, Wang GG, Harrison DE, Xu X. Histone modifications change with age, dietary restriction and rapamycin treatment in mouse brain. Oncotarget. 2015 May 20. [Epub ahead of print]
- Gough SM, Lee F, Yang F, Walker RL, Zhu YJ, Pineda M, Onozawa M, Chung YJ, Bilke S, Wagner EK, Denu JM, Ning Y, Xu B, Wang GG, Meltzer PS, Aplan PD. NUP98-PHF23 is a chromatin modifying oncoprotein that causes a wide array of leukemias sensitive to inhibition of PHD domain histone reader function.Cancer Discovery. 2014 Feb 17. [Epub ahead of print] PMID: 24535671
- Cai L.*, Rothbart S.B., Lu R., Xu B., Chen W.Y., Tripathy A., Rockowitz S., Zheng D., Patel DJ, Allis CD, Strahl B.D., Song J., Wang G.G.An H3K36 methylation engaging Tudor motif of polycomb-like proteins mediates PRC2 complex targeting. Mol Cell. 2013 Feb 7;49(3):571-82. Epub 2012 Dec 27. PMID: 23273982 (*equal contribution)
- Lu R, Wang GG. Tudor: a versatile family of histone methylation 'readers' Trends Biochem Sci. 2013 Sep 10. doi:pii: S0968-0004(13)00133-3. 10.1016/j.tibs.2013.08.002. [Epub ahead of print] - PMID: 24035451
- Konze KD, Ma A, Li F, Barsyte-Lovejoy D, Parton T, Macnevin CJ, Liu F, Gao C, Huang XP, Kuznetsova E, Rougie M, Jiang A, Pattenden SG, Norris JL, James LI, Roth BL, Brown PJ, Frye SV, Arrowsmith CH, Hahn KM, Wang GG, Vedadi M, Jin J. An Orally Bioavailable Chemical Probe of the Lysine Methyltransferases EZH2 and EZH1. ACS Chem Biol. 2013 Apr 24. [Epub ahead of print] PMID: 23614352
- Kumar GS, Chang W, Xie T, Patel A, Zhang Y, Wang G.G., David G, Radhakrishnan I. Sequence requirements for combinatorial recognition of histone H3 by the MRG15 and Pf1 subunits of the Rpd3S/Sin3S corepressor complex. J Mol Biol.2012, 422(4):519-31. PMID: 22728643
- Chi P., Allis C.D. and Wang G.G. Covalent histone modifications: mis-written, mis-erased and mis-interpreted in human cancers. Nat Rev Cancer. 2010,10(7):457-69.
Lab Rooms: Lineberger Cancer Center 31-331
Lab Phone: 919-966-5953