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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DK079019-04
Application #
8230732
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2009-03-01
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
4
Fiscal Year
2012
Total Cost
$105,823
Indirect Cost
$7,839
Name
Northwestern University at Chicago
Department
Urology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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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
Thumbikat, Praveen; Berry, Ruth E; Schaeffer, Anthony J et al. (2009) Differentiation-induced uroplakin III expression promotes urothelial cell death in response to uropathogenic E. coli. Microbes Infect 11:57-65