This proposal describes a 5 year training program for the career development of a Urologic surgeon scientist. The principle investigator is a MD PhD who has completed his clinical training in Urology at the Johns Hopkins University. He will expand his skills in molecular biology, immunology and clinical urology with a combination of training in developmental biology, genetics and urologic pathology. In particular the program will focus on the characterization of novel pathways of androgen regulated prostate development to better understand the pathogenesis of prostatic diseases. Drs. William Isaacs and David Berman will co-mentor the principle investigators scientific development. Dr. Isaacs is an expert in the genetics of benign and malignant prostatic diseases and has a significant history of supporting the career development of many young scientists. Dr Berman is a successful scientist and'urologic pathologist with an expertise in prostate development. Dr Adam Sapirstein, another Johns Hopkins scientist, is an expert in phopholipases and will act as collaborator for this project. He has developed many of the lipid based assays utilized in this proposal and will provide the gene targeted mice described below. In addition, an advisory committee of scientists will provide scientific and career advice. The research proposal focuses on delineating growth programs that induce early prostate organogenesis. Through both gene expression profiling and biochemical techniques we have identified cytosolic phospholipase A2 alpha (cPla2a) as an androgen regulated target of extracellular regulated kinases (Erk1,2). We hypothesize that in the prostate cPla2a is a key target of Erk1,2 and is essential for its development.
The aims of this proposal include: 1) Correlating the timing and cellular distribution of cPla2a expression in relation to Erk1,2 in the developing prostate, 2) Demonstrating activation of cPla2a by Erk1,2 and 3) Evaluating an essential role for cPla2a in early androgen induced prostate development.
These aims will characterize a novel role for cPla2a in the early prostate development and also provide the primary investigator with the training to similarly study, comprehensively, other pathways in prostate development. The Department of Urology at Johns Hopkins is an ideal environment for a career development award. It provides ready access to a diverse array of scientists with expertise in all fields of basic and clinical research and has an outstanding track record of developing and promoting the careers of surgeon scientists. Relevance: Pla2 modulates inflammatory responses. Delineation of the signaling circuitry that normally regulates this enzyme in development is essential for moving forward to understanding, mechanistically, proposed links between prostatic inflammation and pathologies such as benign proliferation and cancer.
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|Schaeffer, E M; Marchionni, L; Huang, Z et al. (2008) Androgen-induced programs for prostate epithelial growth and invasion arise in embryogenesis and are reactivated in cancer. Oncogene 27:7180-91|