The Hooks laboratory studies the molecular mechanisms by which cellular signaling regulates cell function, and how these signaling mechanisms go awry in cancer and central nervous system disorders. Specifically, we study G-protein signaling cascades and their dynamic regulation by activating receptors and deactivating RGS proteins (Regulator of G-protein Signaling proteins). We have a long-standing interest in a family of receptors activated by Lysophosphatidic Acid (LPA) and Sphingosine 1-phosphate (S1P), which are important bioactive lipid growth factors that play important roles in normal physiology and in the development of cancer and inflammatory/immune diseases. We are also exploring the ability of RGS proteins to attenuate these effects and impact disease progression. Research from the our lab has demonstrated that RGS proteins inhibit oncogenic LPA signaling in ovarian cancer cells, blunting LPA-stimulated kinase signaling cascades and growth, migration and survival responses. Our recent studies have focused on the RGS protein RGS10, and we have recently demonstrated that RGS10 is epigenetically silenced in cancer cells, which contributes to the development of chemoresistance. In addition to its role in cancer, RGS10 has been shown to play a critical role in neuroinflammation, a major feature of multiple neural diseases including Parkinson's disease, Multiple Sclerosis, and neuropathic pain. Our current focus is on defining the function and regulation of RGS proteins in cancer and neuroinflammatory disease using a combination of cellular, molecular, and genetic approaches.
RGS10 is an important regulator of cell survival and chemoresistance in ovarian cancer. We recently showed that RGS10 transcript expression is suppressed during acquired chemoresistance in ovarian cancer. The suppression of RGS10 is due to DNA hypermethylation and histone deacetylation, two important mechanisms that contribute to silencing of tumor suppressor genes during cancer progression. Here, we fully investigate the molecular mechanisms of epigenetic silencing of RGS10 expression in chemoresistant A2780-AD ovarian cancer cells. We identify two important epigenetic regulators, HDAC1 and DNMT1, that exhibit aberrant association with RGS10 promoters in chemoresistant ovarian cancer cells.... ►Read More
- Pharmacological Research and Ovarian Cancer
- Publications by Dr. Hooks may be found at PubMed.