Investigators

Summary

One focus of my lab is to investigate the mechanisms regulating androgen receptor (AR) nuclear localization, particularly androgen-independent AR nuclear localization in castration-resistant prostate cancer (CRPC) which is the second leading cause of cancer death in American men.  AR remains to be the key driver in majority of CRPC tumors resistant to the current AR targeting agents. AR nuclear localization is necessary for its function as a transcription factor. According to the classical model of AR nucleocytoplasmic trafficking, AR is present in the cytoplasm in the absence of androgens, which can be imported into the nucleus in the presence of androgens, and the imported AR will be exported upon androgen withdrawal. However, this model is not supported by our recent discovery that imported nuclear AR is degraded, but not exported, upon androgen withdrawal and that unliganded AR can be also imported and rapidly degraded in the nucleus. These findings promoted us to investigate the mechanism of nuclear-specific AR degradation. Identification and characterization of factors responsible for nuclear-specific AR degradation will allow us to investigate if and how these factors are dysregulated in CRPC cells. In addition, we will continue developing novel AR antagonists, with collaborations with experts in medicinal chemistry and structural biology, to identify and characterize small molecules that can inhibit androgen-independent AR nuclear localization in CRPC.