Rita Ghosh, Ph.D.

Associate Professor

Email: ghoshr@uthscsa.edu
Telephone: 210-562-4117
Fax: 210-562-4133

Faculty Profile | Research Profile

Dr. Rita Ghosh received her Ph.D. in Microbiology from the University of HHyderabad India in 1990. In 2005, Dr. Ghosh joined the Department of Urology as an Assistant Professor. Her contributions to the department lead to her promotion to Associate Professor Tenured in 2011. Dr. Ghosh is a member of the NCI designated Cancer Therapy and Research Center and a graduate faculty in the interdisciplinary biomedical Sciences (IBMS) program of the Graduate School of Biomedical Sciences at UT Health San Antonio. She participates in the Cancer Prevention and Population Sciences and Experimental and Developmental Therapeutics programs of the Cancer Center. Additionally, Dr. Ghosh serves as the course director for 2 courses and a co-course director of the IBMS program in the spring and fall semesters. Dr. Ghosh has been a member of the American Society for Cancer Research and the Society for Melanoma Research since 2000; and American Society for Photobiology since 1993. Dr. Ghosh enjoys mentoring graduate students and postdoctoral fellows.

Education

Ph.D., University of Hyderabad, India (1990)
M. Phil., University of Hyderabad, India (1985)
MS, University of Hyderabad, India (1984)

Research

Our principal interest is to understand the interplay between oxidative stress and inflammation in response to endogenous and environmental insults that lead to cancer development and progression. The overall goal is to target these deregulated interactions to develop primary, secondary or tertiary cancer prevention strategies.

Work from our laboratory identified a hitherto unknown role of an antioxidant enzyme NAD[P]H: Quinone Oxidoreductase 1 (NQO1) in prostate cancer. We showed that NQO1 is downregulated in human prostate cancer compared with normal prostate gland and early lesions of prostate cancer. We had previously shown that hormone stimulated rats that develop Prostatic Intraepithelial Neoplasia (PIN) lesions had negligible NQO1 compared with hormone naïve animals. Interestingly, rats receiving antioxidants had comparable NQO1 level to that of hormone naïve animals and significantly decreased the prevalence of PIN. Our recent work identified an unknown role of NQO1 in prostate cancer cell plasticity and its ability to serve as a gatekeeper to inhibit changes that allow hormone-responsive prostate cancer cells to adapt and grow under hormone-deprived conditions. Given all these lines of evidence, we are involved in identifying compounds that can stimulate NQO1 activity to prevent the changes associated with cancer development and progression.

Our laboratory is also interested in gene-environment interactions. This effort is directed towards understanding the role of arsenic (iAs). iAs is the topmost endocrine disruptor on the US substance priority list. Humans consume iAs through contaminated groundwater, through agricultural products, and through industrial products. iAs is released from the body through the urine. Work from our laboratory identified the ability of inorganic arsenic (iAs) to inhibit glucocorticoid receptor (GR) function. The GR is a transcription factor that transactivates genes by binding to the GRE sequence on responsive promoters. GR is involved in activating various inflammatory molecules involved in normal wound healing functions of the urinary bladder. Changes in urinary pH can damage the bladder epithelium and generate an inflammatory response. A functional GR is needed to resolve the inflammatory response. In the absence of inflammation resolution, chronic inflammation and subsequently bladder cancer can ensue. Therefore, our goal is to identify specific inflammatory molecules and cells that are deregulated in response to chronic iAs and the outcomes of these changes in urinary bladder health.

Our group has identified a higher threshold of oxidative stress in melanoma cells compared with melanocytes, which are normal from which melanoma arise. We also found that melanoma cells have a high autophagic flux, which they use to recycle damaged molecules and thus survive. Since melanoma cells have a high level of oxidative stress they also have high levels of damaged macromolecules and organelles that need recycling. This is known to be facilitated by the SQSTM1 gene product (a protein called p62). We have used a novel strategy to thrust melanoma cells above their high oxidative threshold so that these cells are pushed to undergo apoptosis instead of surviving. Our work shows that this change is facilitated by p62 due to its interaction with caspase 8 that is involved in apoptosis. Our current work is focused on the molecular mechanisms through which this change in function is executed as well as developing other molecules that can breach the high oxidative threshold of melanoma cells.

We use a variety of cell culture models of solid tumors and preclinical rodent models (immunocompromised, transgenic and knockout) in our studies. Techniques used to include a combination of genomics, biochemical and molecular biology approaches such as RNA-seq, 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.

Selected Publications

Li G, Rivas P, Bedolla R, Thapa D, Reddick RL, Ghosh R, Kumar AP. Dietary resveratrol prevents the development of high-grade prostatic intraepithelial neoplastic lesions: involvement of SIRT1/S6K axis. Cancer Prev Res (Phila). 2013 Jan;6(1):27-39.
Cardenas E, Ghosh R. Vitamin E: a dark horse at the crossroad of cancer management. Biochem Pharmacol. 2013 Oct 1;86(7):845-52.
Thapa D, Ghosh R. Antioxidants for prostate cancer chemoprevention: challenges and opportunities.
Bedolla RG, Gong J, Prihoda TJ, Yeh IT, Thompson IM, Ghosh R, Kumar AP. Predictive value of Sp1/Sp3/FLIP signature for prostate cancer recurrence. PLoS One. 2012;7(9):e44917.
Payton F, Bose R, Alworth WL, Kumar AP, Ghosh R. 4-Methylcatechol-induced oxidative stress induces intrinsic apoptotic pathway in metastatic melanoma cells. Biochem Pharmacol. 2011 May 15;81(10):1211-8.
Ghosh R, Schoolfield J, Yeh I-Tien, Smith ML, Hursting SD, Chan DC, Lucia MS, and Kumar AP. 2009.  Loss of NADPH Quinone Oxidoreductase (NQO1) in the prostate and enhanced serum levels of cytokine-induced neutrophil chemoattractant-2a (CINC-2a) in hormone-stimulated Noble rats: potential role in PIN development. Translational Oncology 2:65-72. PMC2670573
Thapa DMeng PBedolla RGReddick RLKumar APGhosh R*. NQO1 suppresses NF-κB-p300 interaction to regulate inflammatory mediators associated with prostate tumorigenesis. Cancer Res. 2014 Oct 1;74(19):5644-55. doi: 10.1158/0008-5472.CAN-14-0562. Epub 2014 Aug 14. PMC4184940
Ghosh, R*. Ott, AM, Seetharam, D, Slaga, TJ and Kumar, AP (2003) Cell Cycle Block and Apoptosis induction in a human melanoma cell line following treatment with 2-methoxyestradiol: therapeutic implications? Melanoma Research, 13: 119-127. PMID:12690294

Ghosh R*, Lakshmi Nadiminty, James E Fitzpatrick, William L. Alworth, Thomas J Slaga and Addanki P. Kumar (2004) Eugenol causes melanoma growth suppression through inhibition of E2F1 transcriptional activity. J Biol Chem. 2005; 280(7):5812-9. Epub 2004 Dec 1. PMID:15574415

Payton F, Bose R, Alworth WL, Kumar, AP and Ghosh R* (2011) 4-Methylcatechol-induced oxidative stress induces intrinsic apoptotic pathway in metastatic melanoma cells Biochem Pharmacol 81: 1211-18.  PMC3084369

Hambright HGMeng PKumar APGhosh R*. Inhibition of PI3K/AKT/mTOR axis disrupts oxidative stress-mediated survival of melanoma cells. Oncotarget. 2015 Jan 29. [Epub ahead of print] Oncotarget. 2015; 6(9): 7195-208. PMID:25749517