Paramita M. Ghosh, Ph.D.
Oak Park Research Building
2700 Stockton Blvd
Sacramento, CA 95817
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.
Jathal MK, Steele TM, Siddiqui S, Mooso BA, D'Abronzo LS, Drake CM, Whang YE, Ghosh PM. Dacomitinib, but not lapatinib, suppressed progression in castration-resistant prostate cancer models by preventing HER2 increase. Br J Cancer. 2019 Jul;121(3):237-248.
Shih TC, Liu R, Wu CT, Li X, Xiao W, Deng X, Kiss S, Wang T, Chen XJ, Carney R, Kung HJ, Duan Y, Ghosh PM, Lam KS. Targeting Galectin-1 Impairs Castration-Resistant Prostate Cancer Progression and Invasion. Clin Cancer Res. 2018 Sep 1;24(17):4319-4331.
D'Abronzo LS, Bose S, Crapuchettes ME, Beggs RE, Vinall RL, Tepper CG, Siddiqui S, Mudryj M, Melgoza FU, Durbin-Johnson BP, deVere White RW, Ghosh PM. The androgen receptor is a negative regulator of eIF4E phosphorylation at S209: implications for the use of mTOR inhibitors in advanced prostate cancer. Oncogene. 2017 Nov 16;36(46):6359-6373.
Savoy RM, Chen L, Siddiqui S, Melgoza FU, Durbin-Johnson B, Drake C, Jathal MK, Bose S, Steele TM, Mooso BA, D'Abronzo LS, Fry WH, Carraway KL 3rd, Mudryj M, Ghosh PM. Transcription of Nrdp1 by the androgen receptor is regulated by nuclear filamin A in prostate cancer. Endocr Relat Cancer. 2015 Jun;22(3):369-86.
Mooso BA, Vinall RL, Tepper CG, Savoy RM, Cheung JP, Singh S, Siddiqui S, Wang Y, Bedolla RG, Martinez A, Mudryj M, Kung HJ, Devere White RW, Ghosh PM. Enhancing the effectiveness of androgen deprivation in prostate cancer by inducing Filamin A nuclear localization. Endocr Relat Cancer. 2012 Dec;19(6):759-77.
Chen L, Mooso BA, Jathal MK, Madhav A, Johnson SD, van Spyk E, Mikhailova M, Zierenberg-Ripoll A, Xue L, Vinall RL, deVere White RW, Ghosh PM. Dual EGFR/HER2 inhibition sensitizes prostate cancer cells to androgen withdrawal by suppressing ErbB3. Clin Cancer Res. 2011 Oct 1;17(19):6218-28.
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 Res. 2010 Jul 15;70(14):5994-6003.
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 versus cytoplasmic localization of filamin A in prostate cancer: immunohistochemical correlation with metastases. Clin Cancer Res. 2009 Feb 1;15(3):788-96.
Wang Y, Mikhailova M, Bose S, Pan CX, deVere White RW, Ghosh PM. Regulation of androgen receptor transcriptional activity by rapamycin in prostate cancer cell proliferation and survival. Oncogene. 2008 Nov 27;27(56):7106-17.
Wang Y, Kreisberg JI, Bedolla RG, Mikhailova M, deVere White RW, Ghosh PM. A 90 kDa fragment of filamin A promotes Casodex-induced growth inhibition in Casodex-resistant androgen receptor positive C4-2 prostate cancer cells. Oncogene. 2007 Sep 6;26(41):6061-70.
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 Akt activation. Clin Cancer Res. 2007 Jul 1;13(13):3860-7.
Kreisberg JI, Malik SN, Prihoda TJ, Bedolla RG, Troyer DA, Kreisberg S, Ghosh PM. Phosphorylation of Akt (Ser473) is an excellent predictor of poor clinical outcome in prostate cancer. Cancer Res. 2004 Aug 1;64(15):5232-6.
- PMI 200 Foundations in Research (Fall)
- BCB 256 Cell and Molecular Biology of Cancer (Winter)
- BCB 298 Signal Transduction Pathways (Spring)
Professional Courses for Medical Students