This proposal describes a five-year training program for the development of an academic career in studying urologic diseases. The Principal Investigator has completed a PhD in molecular disease pathogenesis, postdoctoral training in diseases of the urinary tract and is presently in a period of transition as a junior faculty member at Northwestern University. This proposed program will lead to an understanding of the mechanisms of inflammation in the prostate gland. Dr. Anthony Schaeffer will mentor the Principal Investigator's scientific development. Dr. Schaeffer is a recognized leader in the fields of prostate inflammation and infectious diseases of the urinary tract. He is the Chair of Urology at Northwestern University and has trained numerous researchers and students. To further assist in providing guidance, an advisory committee of highly regarded medical scientists will be established to periodically review progress of the principal investigator. Research will focus on characterizing the role of toll-like receptors (TLR's) in prostate inflammatory responses and identifying the component pathways involved. Recent work by the principal investigator has shown that prostate epithelial cells express pattern recognition receptors (PRRs) like TLR4 that respond to inflammatory stimuli. The proposed studies will examine how TLR4 signaling occurs in prostate epithelial cells in response to lipopolysaccharide (LPS) from E. coli. In vitro culture models and a novel in vivo murine bacterial prostatitis model will be used. In culture, transcriptional factor activation will be studied following systematic siRNA silencing of the TLR4 signaling pathways. In vivo, chimeric mice will be used to determine the site of TLR4 functional immunity to E. coli. The Department of Urology at Northwestern University provides an ideal setting for training with close collaboration between clinical and basic scientists creating an environment conducive to the development of an academic career.

Public Health Relevance

The proposed research will lead to a better understanding of the mechanisms of a number of urologic diseases including prostatitis and benign prostatic hyperplasia (BPH), conditions affecting millions of men.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Scientist Development Award - Research & Training (K01)
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Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
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Northwestern University at Chicago
Schools of Medicine
United States
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Murphy, Stephen F; Schaeffer, Anthony J; Done, Joseph et al. (2015) IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP). PLoS One 10:e0125623
Wong, Larry; Done, Joseph D; Schaeffer, Anthony J et al. (2015) Experimental autoimmune prostatitis induces microglial activation in the spinal cord. Prostate 75:50-9
Roman, Kenny; Done, Joseph D; Schaeffer, Anthony J et al. (2014) Tryptase-PAR2 axis in experimental autoimmune prostatitis, a model for chronic pelvic pain syndrome. Pain 155:1328-38
Quick, Marsha L; Done, Joseph D; Thumbikat, Praveen (2013) Measurement of tactile allodynia in a murine model of bacterial prostatitis. J Vis Exp :e50158
Quick, Marsha L; Wong, Larry; Mukherjee, Soumi et al. (2013) Th1-Th17 cells contribute to the development of uropathogenic Escherichia coli-induced chronic pelvic pain. PLoS One 8:e60987
Quick, Marsha L; Mukherjee, Soumi; Rudick, Charles N et al. (2012) CCL2 and CCL3 are essential mediators of pelvic pain in experimental autoimmune prostatitis. Am J Physiol Regul Integr Comp Physiol 303:R580-9
Done, Joseph D; Rudick, Charles N; Quick, Marsha L et al. (2012) Role of mast cells in male chronic pelvic pain. J Urol 187:1473-82
Rudick, Charles N; Berry, Ruth E; Johnson, James R et al. (2011) Uropathogenic Escherichia coli induces chronic pelvic pain. Infect Immun 79:628-35
Thumbikat, Praveen; Shahrara, Shiva; Sobkoviak, Rudina et al. (2010) Prostate secretions from men with chronic pelvic pain syndrome inhibit proinflammatory mediators. J Urol 184:1536-42
Thumbikat, Praveen; Berry, Ruth E; Zhou, Ge et al. (2009) Bacteria-induced uroplakin signaling mediates bladder response to infection. PLoS Pathog 5:e1000415

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