Assistant Professor of Biochemistry and Biophysics, UNC-CH
PHD - University of California, San Diego
HONORS & AWARDS
- UNC Jefferson-Pilot Fellowships in Academic Medicine Award - 2013
- Martin D. Abeloff, MD V Scholar Award, the V Foundation for Cancer Research - 2011
- NIH/NCI Howard Temin Pathway to Independence Award in Cancer Research- 2010
- Leukemia & Lymphoma Society Fellow Award - 2008
- C.H. Li Memorial Fund Scholar Award, Rockefeller University - 2007
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.
- Cai L., Rothbart S.B., Lu R., Xu B., Chen W.Y., Tripathy A., Rockowitz S., Zheng D., Strahl B.D., Song J., Wang G.G. An H3K36 methylation engaging Tudor motif of polycomb-like proteins mediates PRC2 complex targeting. Molecular Cell 2012 Dec 22. doi:pii: S1097-2765(12)00983-5. 10.1016/j.molcel.2012.11.026. [Epub ahead of print] PMID: 23273982
- 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.
- Wang G.G., Song J., Wang Z., Dormann H.L., Casadio F., Li H., Luo J., Patel D.J. and Allis C.D . Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger. Nature. 2009, 459(7248):847-851. [News & Views at Nat Rev Cancer 2009(9):461, Nat Chem Biol. 2009;5(7):457, & Science News 2009,175 (12):11]
- Milne T.A., Kim J., Wang G.G., Wang Z., Ren X., Basrur V., Ruthenburg A.J., Elenitoba-Johnson K., Patel D.J., Roeder R.R. and Allis C.D. 2010. Multiple Interactions Recruit MLL1 and MLL1 Fusion Proteins to the HOXA9 Locus in Leukemogenesis. Mol Cell. 2010, 25; 38(6):853-63.
- Wang Z., Song J., Milne T.A., Wang G.G., Li H., Allis C.D., and Patel D.J. Proline Isomerization in MLL1 PHD3-Bromo Cassette Connects H3K4me Readout to CyP33 and HDAC-Mediated Repression. Cell. 2010, 141(7): 1183-94.
- Wang G.G., Allis C.D. and Chi P. 2007. Chromatin remodeling and cancer: covalent histonemodifications. Trends Mol. Med., 13(9): 363-72.
- Wang G.G., Allis C.D. and Chi P. 2007. Chromatin remodeling and cancer: ATP-dependentchromatin remodeling. Trends Mol. Med., 13(9): 373-80.
- Wang G.G., Cai L., Pasillas M.P. and Kamps M.P. NUP98-NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis. Nat Cell Biol. 2007,9(7): 804-812.
- Wang G.G., Calvo K.R., Pasillas M.P., Sykes D.B., Hacker H. and Kamps M.P. Quantitative production of macrophages or neutrophils ex vivo using conditional Hoxb8. Nat Methods, 2006,3(4): 287-93. [News and Views at Nat Methods 2006; 3(4): 248 – 249.]
- Wang G.G., Pasillas M.P. and Kamps MP. Persistent transactivation by Meis1 replaces Hox function in myeloid leukemogenesis models: evidence for co-occupancy of Meis1-Pbx and Hox-Pbx complexes on promoters of leukemia-associated genes. Mol Cell Biol. 2007, 26(10): 3902-16.
- Wang G.G., Pasillas M.P. and Kamps M.P. Meis1 programs transcription of FLT3 and cancer stem cell character, using a mechanism that requires interaction with Pbx and a novel function of the Meis1 C-terminus. Blood 2005, 106(1):254-64. [Editors' views at Blood 2005; 106(1):6-7.]
450 West Drive,
Campus Box # 7295
Lineberger Cancer Center, 31-327
Chapel Hill, NC 27599
Lab Location: 31-331 Lineberger