Research Interests
G protein-coupled receptors (GPCRs) are major regulators of important cellular responses. Aberrant GPCR signaling causes many human diseases including cancer. Regulators of G-protein Signaling (RGS) proteins inhibit GPCR signaling, thus playing a key role in the regulation of GPCR functions in vivo. The long-term goal of my lab is to elucidate the functions and mechanisms of RGS proteins in prostate tumorigenesis and metastasis.
Prostate cancer is the most common cancer in American men and acquisition of androgen independence by prostate cancer is the key problem of prostate cancer progression. Several lines of evidence suggest that androgen-independent activation of androgen receptor (AR) is one underlying mechanism of androgen independence. We recently reported that RGS2, a member of the RGS protein superfamily, inhibits androgen-independent AR signaling in prostate cancer cells. We are currently investigating the role of dysregulation of RGS2 in androgen-independent progression of prostate cancer by using both in vitro and in vivo models. Our studies will significantly advance understanding of how dysregulation of RGS proteins causes GPCR-mediated androgen-independent AR activation, thus contributing to prostate cancer progression to androgen-independent disease. Such knowledge will ultimately aid in the design of novel therapeutic approaches for hormone-refractory prostate cancers. 
Metastasis, the hormone stimulated migration of cancer cells from the primary tumor and their subsequent invasion and proliferation in healthy tissues, is the chief cause of mortality in prostate cancer. Some of the hormones that stimulate metastasis act via GPCRs. Mounting evidence suggests that Rac-dependent directed cell migration plays a critical role in prostate cancer metastasis. We recently found that migration of prostate cancer cells was enhanced by P-Rex1, a Rac-specific activator that is stimulated by Gi-coupled GPCRs. P-Rex1 expression was correlated with the metastatic potential of established human prostate cancer cell lines, and metastatic human prostate cancer specimens expressed significantly higher levels of P-Rex1 protein compared to matched normal prostate tissues and localized prostate tumors. We are now attempting to identify the factors that trigger prostate cancer migration and are investigating the molecular mechanisms underlying prostate cancer metastasis. Our studies could lead to the development of novel anti-metastasis strategies for preventing and halting prostate cancer progression.
