Department of Pharmacology & Chemical Biology at the University of Pittsburgh
Zhou Wang, PhD
Professor and UPMC Chair in Urological Research
Shadyside Medical Center, Suite G40
5200 Centre Ave., Pittsburgh, PA 15232

Phone: 412-623-3903

Fax: 412-623-3904

BS (Biology), University of Science and Technology of China, China, 1983
PhD (Molecular Biology), University of Pittsburgh Pittsburgh, PA, 1990

Research Areas
Cancer Pharmacology
Signal Transduction
Receptor Pharmacology
Drug Discovery
Photo of Zhou Wang, PhD

Dr. Wang’s lab is interested in the mechanism of androgen action and the roles of androgens in benign and cancerous prostate growth.  The long-term objective of his research is to identify new targets for the treatment and prevention of prostate cancer and benign prostatic hyperplasia (BPH).

One area of research is to determine the role of androgen-responsive genes in the prostate.  Dr. Wang’s lab recently showed that one of the androgen-responsive gene, U19/Eaf2, is a tumor suppressor.  U19/Eaf2 downregulation and loss of heterozygosity were observed in more than 80% of advanced human prostate cancer specimens examined, indicating that Eaf2 likely blocks prostate cancer progression.  Overexpression of Eaf2 induced apoptosis of prostate cancer cell lines, both in vitro and in vivo, while Eaf2 gene knockout in mice resulted in tumors in multiple tissues. These findings demonstrate that Eaf2 indeed functions as a tumor suppressor.  His current research focuses on U19/Eaf2-binding partners and Eaf2-downstream genes to better understand U19/Eaf2 function in prostate carcinogenesis and to elucidate the mechanisms by which androgens can modulate prostate cancer progression. 

The other research is to elucidate the mechanism of androgen receptor intracellular trafficking.  In androgen-sensitive prostate cancer cells, AR remains in the cytoplasm in the absence of androgens. Androgens induce nuclear translocation of AR, resulting in the transactivation of androgen-responsive genes and prostate cancer proliferation. However, in castration-resistant prostate cancer cells, AR localizes to the nucleus in the absence of androgens. Importantly, androgen-independent AR nuclear localization is a prerequisite for AR to undergo androgen-independent activation. As this activation likely plays a critical role in the development of castration-resistance, elucidating the mechanism of AR androgen-independent nuclear localization may provide insights into disease progression. A better understanding of how prostate cancer transforms from an androgen-sensitive to a castration-resistant state will provide new treatment targets — a vital endeavor, since no curative therapy exists for advanced disease.

Important Publications
Liu J, LE Pascal, S Isharwal, D Metzger, R Ramos Garcia, J Pilch, S Kasper, K Williams, PH Basse, JB Nelson, P Chambon and Z Wang Regenerated luminal epithelial cells are derived from pre-existing luminal epithelial cells in adult mouse prostate.  Molecular Endocrinology 25:1849,1857, 2011.
Cai L, BL Phong, A Fisher and Z Wang.  Regulation of fertility, survival and cuticle collagen function by C. elegans eaf-1 and ell-1 genes.  Journal of Biological Chemistry 286:35915-35921, 2011. 
Pascal LE, J Ai, LH Rigatti, AK Lipton, W Xiao, JR Gnarra and Z Wang.  EAF2 loss enhances angiogenic effects of Von Hippel-Lindau heterozygosity on the murine liver and prostate.  Angiogenesis 13:331-343, 2011.
Su F, LE Pascal, W Xiao and Z Wang.  Tumor suppressor U19/EAF2 regulates thrombospondin-1 expression via P53.  Oncogene 29:421-431, 2010.
Gupta S, Y Wang, R Ramos-Garcia, D Shevrin, JB Nelson and Z Wang.  Inhibition of 5a-reductase enhances testosterone-induced expression of U19/Eaf2 tumor suppressor during the regrowth of LNCaP xenograft tumor in nude mice.  The Prostate 70:1575-1585, 2010.
Ai J, Y Wang, JA Dar, J Liu, L Niu, J Nelson and Z Wang.  HDAC6 regulates androgen receptor hypersensitivity and nuclear localization via modulating Hsp90 acetylation in castration-resistant prostate cancer.  Mol Endocrinol 23: 1963-1972, 2009.

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