Department of Cancer Biology and Genetics
888 Biomedical Research Tower
460 W. 12th Avenue
Columbus, OH 43210
Phone: (614) 247-1609
Fax: (614) 688-4181
My laboratory is primarily interested in understanding the genomic function of androgen receptor (AR) in the development and progression of prostate cancer. AR is a ligand-dependent transcription factor belonging to the nuclear hormone receptor (NR) superfamily. Recently, we have utilized high-throughput techniques such as ChIP-exo (chromatin immunoprecipitation-exonuclease combined with high-throughput sequencing) and ChIP-seq (ChIP combined with high-throughput sequencing) to globally identify AR-bound genomic sites and precisely define AR binding motifs leading to target gene expression at various stages of prostate cancer, including androgen-dependent prostate cancer (ADPC) and castration-resistant prostate cancer (CRPC). By combining AR binding maps with gene expression profiles, we have begun to understand how AR regulates target gene networks in ADPC and CRPC.
We are extending our view from transcriptional regulation by AR alone to include a wider view of transcription regulation in prostate cancer. These efforts have included studies of
transcription factor-centered, multi-layer transcription regulatory networks in prostate cancer, which involve transcription factors (e.g. AR, FOXA1 and GATA2), transcription coactivators (e.g. Mediator and histone acetyltransferases), and epigenetic regulators (e.g. histone modifications and chromatin looping). These efforts are leading to many exciting results that will inform the development of more effective options for targeting AR activity throughout all stages of prostate cancer. Our results have also indicated that several additional, and perhaps druggable, factors play an AR-independent role in supporting prostate cancer growth at various stages of the disease.
Finally, our understanding of AR genomic activity has allowed us to extend our investigations to study the genomic functions of other NRs (e.g. glucocorticoid receptor) in non-prostatic cancers, such as breast cancer.
Capital University of Medical Sciences, Beijing, China, 1994, B.Med. in Clinical Medicine
University of Maryland, Baltimore, 2002, Ph.D. in Physiology
Rutgers University-Robert Wood Johnson Medical School, 2003, Postdoctoral Fellow in Physiology
Dana-Farber Cancer Institute and Harvard Medical School, 2008, Postdoctoral Fellow/Instructor in Molecular and Cellular Oncology
2002 Dr. Arthur Schwartz Award for Academic Advancement, University of Maryland, Baltimore
2003 Member, Honor Society of Phi Kappa Phi
2004 Postdoctoral Prostate Cancer Research Award, Department of Defense (DoD)
2006 Career Development Award in Prostate Cancer Research, Dana-Farber/Harvard Cancer Center
2006 Keystone Symposia Scholarship, NIDDK, NIH
2007 Howard Temin Pathway to Independence Award in Cancer Research (K99/R00), NCI, NIH
2007 Travel Grant Award, The Endocrine Society
2008 First Prize, Poster Presentation Award, Dana-Farber Cancer Institute/Johns Hopkins Medical Institute,
Memorial Sloan-Kettering Cancer Center Prostate Cancer Program Retreat, Rhode Island
2010 Young Investigator Award, Society for Basic Urologic Research
2011 V Scholar Award, The V Foundation for Cancer Research
2012 Early Investigators Award, The Endocrine Society
Wang Q, Carroll JS, Brown M. Spatial and temporal recruitment of androgen receptor and its coactivators involves chromosomal looping and polymerase tracking. Mol Cell, 19:631-642, 2005.
Wang Q, Li W, Liu, XS, Carroll JS, Jänne OA, Keeton EK, Chinnaiyan AM, Pienta KJ, Brown M. A hierarchical network of transcription factors governs androgen receptor dependent prostate cancer growth. Mol Cell, 27:380-392, 2007. (Mol Cell Featured Article)
Wang Q*#, Li W#, Zhang Y, Yuan X, Xu K, Yu J, Chen Z, Beroukhim R, Wang H, Wu T, Lupien M, Carroll JS, Manrai AK, Jänne OA, Balk SP, Mehra R, Chinnaiyan AM, Rubin MA, True L, Fiorentino M, Fiore C, Loda M, Kantoff PW, Liu XS*, Brown M*. Androgen-receptor regulates a distinct transcription program in androgen-independent prostate cancer. Cell, 138:245-256, 2009. (* Corresponding authors, # First authors) (Cell Featured Article).
Chen Z, Zhang C, Wu D, Chen H, Rorick A, Zhang X, and Wang Q. Phospho-MED1-enhanced UBE2C locus looping drives castration-resistant prostate cancer growth. EMBO J, 30:2405-2419, 2011.
Wang H, Zhang C, Rorick A, Wu D, Chiu M, Thomas-Ahner J, Chen Z, Clinton SK, Chan KK, and Wang Q. CCI-779 inhibits cell-cycle G2-M progression and invasion of castration-resistant prostate cancer via attenuation of UBE2C transcription and mRNA stability. Cancer Res, 71: 4866-4876, 2011.
Zhang C, Wang L, Wu D, Chen H, Chen Z, Thomas-Ahner J, Eeckhoute J, Yu J, Luo J, Brown M, Clinton SK, Nephew KP, Huang THM, Li W, and Wang Q. Definition of a FoxA1 cistrome that is crucial for G1-S phase cell-cycle transit in castration-resistant prostate cancer. Cancer Res, 71:6738-6748, 2011.
Wu D., Zhang C, Shen Y, Nephew KP, and Wang Q. Androgen receptor-driven chromatin looping in prostate cancer. Trends Endocrinol Metab, 22:474-480, 2011.
Cai C, Wang H, He HH, Chen S, He L, Ma F, Mucci L, Wang Q, Fiore C, Sowalsky AG, Loda M, Liu XS, Brown M, Balk SP, Yuan X. ERG induces androgen receptor-mediated regulation of SOX9 in prostate cancer. J Clin Invest, 123: 1109-1122, 2013.
Ye Z, Chen Z, Lan X, Hara S, Sunkel B, Huang THM, Elnitski L, Wang Q*, and Jin VX*. Computational analysis reveals a correlation of exon-skipping events with splicing, transcription and epigenetic factors. Nucleic Acids Res, 42: 2856-2869, 2014. (* Corresponding authors).
Wu D, Sunkel B, Chen Z, Li Q, Cassandra G, Ye Z, Ke J, Chen H, Nephew KP, Huang THM, Liu Z, Jin VX and Wang Q. Three-tiered role of the pioneer factor GATA2 in promoting androgen-dependent gene expression in prostate cancer. Nucleic Acids Res, 42: 3607-3622, 2014. (NAR Breakthrough Article).
Chen Z, Lan X, Thomas-Ahner JM, Wu D, Liu X, Ye Z, Wang L, Sunkel B, Grenade C, Chen J, Zynger DL, Yan PS, Huang, J, Nephew KP, Huang THM, Lin S, Clinton SK, Li W, Jin VX and Wang Q. Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer. EMBO J, 34: 502-516, 2015.
He H, Li W, Liyanarachchi S, Srinivas M, Wang Y, Akagi K, Wang Y, Wu D, Wang Q, Jin V, Symer DE, Shen R, Phay J, Nagy R, and de la Chapelle. Multiple functional variants in long-ranger enhancer elements contribute to the risk of SNP rs965513 in thyroid cancer. Proc Natl Acad Sci USA, 112: 6128-6133, 2015.
Liu H, Tang X, Srivastava A, Pecot T, Daniel P, Hemmelgarn B, Reyes S, Fackler N, Bajwa A, Kladney R, Koivisto C, Chen Z, Wang Q, Huang K, Machiraju R, Saenz-Robles MT, Cantalupo P, Pipas JM and Leone G. Redeployment of Myc and E2f1-3 drives cancer-like cell cycles. Nat Cell Biol, 17: 1036-1048, 2015.
Chen K, Chen Z, Wu D, Zhang L, Lin X, Su J, Rodriguez B, Xi Y, Xia Z, Chen X, Shi X, Wang Q* and Li W*. Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor-suppressor genes. Nat Genet, 47:1149-1157, 2015 (* Corresponding authors).
Chen Z*, Lan X, Wu D, Sunkel B, Ye Z, Huang J, Liu Z, Clinton SK, Jin VX and Wang Q*. Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer. Nat Commun, 6: 8323, 2015 (* Corresponding authors).