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.
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