Research Faculty Bio
Rita Ghosh, Ph.D.
Research Goals of the laboratory:
Our overall goal is to study deregulation of DNA damage signaling and cell cycle progression in cancer and use these pathways as molecular targets to develop strategies for cancer prevention and or therapy. A variety of cell culture and animal models are used our studies to address key questions. The in vitro studies use a combination of genomics and molecular biology approaches including microarray analysis, RNA interference, quantitative real-time RT-PCR, reporter gene assays, in vitro transcription, measurement of DNA strand breaks and oxidative DNA damage, proliferation and apoptosis assays, immunoprecipitation and Western blotting. Preclinical animal models include nude mouse and transgenic mouse models that develop cancer.
The goal of one of our current projects is to examine the involvement of NADPH: Quinone Oxidoreductase (NQO1), a phase II detoxifying enzyme in hormone-induced prostate tumorigenesis. Our published results show that NQO1 level in the prostate from hormone stimulated rats that develop Prostatic Intraepithelial Neoplasia (PIN) is undetectable compared to hormone naïve animals. Interestingly, rats receiving antioxidants had comparable NQO1 level to that of hormone naïve animals and significantly decreased prevalence of PIN. Further, the existence of oxidative stress markers in prostate cancer patients suggests that oxidative stress signaling may be a reasonable target to prevent progression of indolent prostate cancer to clinically significant disease. Therefore we are using cocktails of antioxidants as tools to quench hormone-induced oxidative stress molecules and studying its effect on the regulation of NQO1 and its ability to prevent prostate cancer progression in animal models.
Currently we are also studying modulation of the p16/Rb/E2F axis in melanoma. Specifically we are examining the role of the E2F transcription factor family in melanoma progression. Different members of this family play contrasting as well as overlapping roles in normal and cancer cells. In addition to E2F1 hyperactivity, its copy number is also increased in melanoma. Hyperactivity of E2F1 is believed to confer proliferative capability to melanoma cells. Our studies are focused on understanding the mechanisms that lead to E2F stability in melanoma. Ongoing studies are looking at post-translational modification of E2F1 as a mechanism of E2F1 stability in order to develop it as a target to inhibit proliferation of melanoma cells. We are also using naturally occurring small molecule inhibitors of E2F activity to probe the different roles of the E2Fs in DNA damage signaling, apoptosis, invasion and their interactions with the pocket proteins in carcinogenesis.
A third project is examining the role of mutant p53 in DNA damage signaling, check point arrest and senescence induction during bladder carcinogenesis. We are specifically studying the involvement of transactivation domain and DNA binding domain mutations in these biological functions in bladder cancer. We are also using natural compounds to target senescence induction as a mechanism to inhibit recurrent bladder cancer. Our preliminary work demonstrates a potential for several polyphenolic compounds as inhibitors of Telomerase level and activity in non-muscle invasive bladder cancer that tends to frequently recur.