Ghosh, Paramita M. - University of California, Davis - Department of Biochemistry and Molecular Medicine

研究领域

My chief topic of research over the last six years has been the elucidation of signal transduction pathways leading to the development of androgen-independent prostate cancer. Prostate cancer is a disease of the aging male. In a normal adult prostate, there is a balance between the rate of proliferation and the rate of apoptosis or cell death. In prostate cancer, this balance is lost, resulting in excessive proliferation, decreased apoptosis or both. My current research is based on the initial observation from our laboratory that in poorly differentiated prostate cancers, Akt, a downstream target of the phosphatidylinositol 3-kinase (PI3K) pathway, is highly phosphorylated. Based on these observations, I have investigated, over the last few years, the role of Akt in the progression of prostate cancer to an androgen-independent state. Currently, I am engaged in studying signal transduction pathways both upstream and downstream of Akt. Upstream of Akt, I am studying the effect of receptor tyrosine kinases and their effects on both the PI3K and the MAPK cell signaling pathways, while downstream of Akt, I am studying the cross-talk with the androgen receptor pathway, and the effects of aging on the development of prostate cancer. At present, our targets of investigation include the erbB family of receptor tyrosine kinases, the andogen receptor, the cytoskeletal scaffolding molecule Filamin A which is known to be an androgen receptor coregulator and components of the signal transduction pathways downstream of Ras (including the mitogen activated protein kinases) and the mammalian target of rapamycin (mTOR), including p70 S6 kinase, 4E-BP1 and e1F-4G.

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Bedolla R, Prihoda TJ, Kreisberg JI, Malik SN, Krishnegowda NK, Troyer DA, Ghosh PM. Determining risk of biochemical recurrence in prostate cancer by immunohistochemical detection of PTEN expression and Aktactivation. Clin. Cancer Res., 2007. 13(13): 3860-3867. Wang, Y., Kreisberg, J.I., Bedolla, R., Mikhailova, M., deVere White, R.W. and Ghosh, P.M. A 90kDa fragment of Filamin A promotes Casodexinduced growth inhibition in Casodex-resistant androgen-receptor positive C4-2 prostate cancer cells. Oncogene, 2006. 26: 6061-6070. Shi, X.-B., Xue, L. Tepper, C.G., Gandour-Edwards, R., Ghosh, P., Kung, H.J. and deVere White, R.W. The oncogenic potential of a prostate cancer-derived androgen receptor mutant. The Prostate, 2007. 67(6): 591-602. Vinall, R.L., Hwa, K., Ghosh, P., Pan, C-X., Lara, P.N. Jr. and deVere White, R.W. Combination Treatment Of Prostate Cancer Cell Lines With Bioactive Soy Isoflavones (GCP) And Perifosine Causes Increased Growth Arrest And/Or Apoptosis. Clinical Cancer Res., 2007. 13: 6204-6216. Wang, Y., Kreisberg, J.I. and Ghosh, P.M. Cross-talk between the Androgen Receptor and the Phosphatidylinositol 3-kinase/Akt pathway in Androgen-Independent Prostate Cancer. Current Cancer Drug Targets., 2007. 7: 591-604. Kamat, A., Ghosh, PM, Glover, RL, Zhu, B, Yeh, CK, Choudhury, GG and Katz, MS. Reduced Expression of Epidermal Growth Factor Receptors in. Journal of Gerontology, 2008. 63(7): 683-692. Wang, Y, Mikhailova, M, deVere White, RW, and Ghosh, PM. Regulation of androgen receptor transcriptional activity by rapamycin. Oncogene, 2008. 27(56): 7106-7117. Chamie, K, Ghosh, PM, Koppie, TM, Romero, V, Troppmann, C,and deVere White, RW. The effect of sirolimus on PSA kinetics in male renal transplant recipients without prostate cancer. American Journal of Transplantation, 2008. 8(12): 2668-2673.