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.
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 rat liver during aging. 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.
Bedolla RG, Wang Y, Asuncion A, Chamie K, Siddiqui S, Mudryj MM, Prihoda TJ, Siddiqui J, Chinnaiyan AM, Mehra R, de Vere White RW, Ghosh PM. Nuclear vs Cytoplasmic localization of Filamin A in Prostate Cancer: Immunohistochemical Correlation with Metastases. Clinical Cancer Research, 15(3): 788-796, 2009.
Khan IH, Ghosh PM, Zhao J, Ziman M, Sweeney C, Kung HJ and Luciw PA. Microbead Arrays for the Analysis of ErbB Receptor Tyrosine Kinase Activation and Dimerization in Breast Cancer Cells. ASSAY and Drug Development Technologies, 8(1): 27-36, 2010.
Chen H, Libertini SJ, Wang Y, Kung HJ, Ghosh PM, Mudryj M. ERK Regulates Calpain 2 Induced AR Cleavage To LMW Forms in CWR22 Relapsed Prostate Tumor Cell Lines. J Biol Chem, 285(4): 2368-74, 2010.
Chen L, Siddiqui S, Bose S, Mooso B, Asuncion A, Bedolla RG, Vinall R, Tepper CG, Gandour-Edwards R, Shi X, Lu XH, Siddiqui J, Chinnaiyan AM, Mehra R, Devere White RW, Carraway KL 3rd, Ghosh PM.. Nrdp1-mediated regulation of ErbB3 expression by the androgen receptor in androgen-dependent but not castrate–resistant prostate cancer cells. Cancer Research, 70(14): 5994-6003, 2010.
Chen H, Libertini SJ, George M, Dandekar S, Tepper CG, Al-Bataina B, Kung H-J, Ghosh PM, Mudryj M. Genome-wide analysis of androgen receptor binding and gene regulation in two CWR22-derived prostate cancer cell lines. Endocrine-related cancers, 17(4): 857-873, 2010.
Mooso BA, Loredo GA, Madhav A, Johnson S, Roy M, Moore ME, Moy CV, Mehta RG, Vaughan ATM, Ghosh PM. Androgen Receptor regulation of Vitamin D receptor in response of prostate cancer cells to 1α(OH)D5. Genes & Cancer, 2010, in press.
Upper division courses
- 192 Internship in Biological Chemistry
- 198 Group Study
- 199 Special Study for Advanced Undergraduates
Professional courses for medical students
- 231 Biomedical NMR (same as BPH 231)
- 291 Human Genetics Seminar
- 298 Group Study
- 299 Research
- 410A Molecular and Cell Biology
- 410B Cell Biology and Metabolism
- 498 Group Study
- 499 Research