This proposal describes a four-year training program leading to the development of an academic career in studying diseases of the prostate. The Principal Investigator, Bo Cen, has completed a PhD in molecular and cellular biology, postdoctoral trainings in cancer research and is presently in a period of transition as a junior faculty member at the Medical University of South Carolina. He is applying for the mentored-K01 at this stage in his career because (1) he has developed focused research results in an important area of prostate pathology, and (2) his current institution has openings for faculty members with this training in prostate biology. This proposed program will combine training in normal prostate biology, prostate genetics, and additional research experience, leading to an understanding of the mechanisms of epithelium growth stimulation in the prostate gland. Additionally, he will gain experience running a laboratory including budgeting and project development. His primary mentor, Dr. Andrew S. Kraft, Director of Hollings Cancer Center at Medical University of South Carolina, has trained over 30 PhDs, and has worked extensively to understand prostate cell growth and death. Drs. Scott Cramer, a prostate biologist;Simon Hayward, a benign prostate hyperplasia specialist;Dennis Watson, a molecular geneticist;and Dr. Stephen Savage, a urologist, will function as co- mentors. This application proposes two years of specific training to further develop Dr. Cen's biologic and genetic expertise at which time newly constructed buildings with laboratory space to accommodate Dr. Cen will be available. The latter two years of this proposed career development plan will be focused on establishing Dr. Cen's independently funded laboratory. Dr. Cen's research will focus on characterizing the role of Pim family kinases in prostate epithelium growth and identifying the component pathways involved in causing benign hyperplasia. He has recently found that prostate epithelium that overexpress Pim are stimulated to grow by hormones that would normally inhibit prostate growth. To facilitate further examination of this process in culture, a novel prostate cell model will be used to study Pim's role in stromal-epithelial interaction and stimulating stromal growth. In vivo, both transgenic and knockout mice will be used to determine important function of Pim kinases in epithelium proliferation. With close collaborations between clinical and basic scientists working in the area of urologic biology and as an NIH Clinical and Translational Science Award funded institution, the Medical University of South Carolina provides an ideal setting for training and academic career development.
The proposed research will lead to a better understanding of the mechanisms of benign prostatic hyperplasia (BPH), effecting more than 50% of all men in their sixties and up to 90% of men in their seventies and eighties. Currently there are limited effective ways to prevent and/or treat BPH and the lower urinary tract problems it causes.
|An, Ningfei; Xiong, Ying; LaRue, Amanda C et al. (2015) Activation of Pim Kinases Is Sufficient to Promote Resistance to MET Small-Molecule Inhibitors. Cancer Res 75:5318-28|
|Zemskova, Marina Y; Song, Jin H; Cen, Bo et al. (2015) Regulation of prostate stromal fibroblasts by the PIM1 protein kinase. Cell Signal 27:135-46|
|Cen, Bo; Xiong, Ying; Song, Jin H et al. (2014) The Pim-1 protein kinase is an important regulator of MET receptor tyrosine kinase levels and signaling. Mol Cell Biol 34:2517-32|
|Cen, Bo; Mahajan, Sandeep; Wang, Wenxue et al. (2013) Elevation of receptor tyrosine kinases by small molecule AKT inhibitors in prostate cancer is mediated by Pim-1. Cancer Res 73:3402-11|
|Cen, Bo; Mahajan, Sandeep; Zemskova, Marina et al. (2010) Regulation of Skp2 levels by the Pim-1 protein kinase. J Biol Chem 285:29128-37|