Role of Pattern Recognition Receptors in Prostate Epithelial Inflammation

描述（由申请人提供）： 该提案描述了一个为期五年的培训计划，用于研究泌尿系统疾病的学术生涯的发展。主要研究者已经完成了分子疾病发病机制的博士学位，尿路疾病的博士后培训，目前正处于西北大学初级教员的过渡期。该计划将导致对前列腺炎症机制的理解。Anthony Schaeffer博士将指导首席研究员的科学发展。Schaeffer博士是前列腺炎症和泌尿道感染性疾病领域公认的领导者。他是西北大学泌尿外科的主席，并培养了许多研究人员和学生。为了进一步协助提供指导，将设立一个由德高望重的医学科学家组成的咨询委员会，定期审查主要研究者的进展情况。研究将集中在表征toll样受体（TLR）在前列腺炎症反应中的作用，并确定所涉及的组成途径。主要研究者最近的工作表明，前列腺上皮细胞表达模式识别受体（PRRs），如TLR4，对炎症刺激作出反应。本研究将探讨前列腺上皮细胞对大肠杆菌脂多糖（LPS）的反应中，TLR4信号是如何发生的。杆菌将使用体外培养模型和一种新的体内小鼠细菌性前列腺炎模型。在培养物中，将在TLR4信号通路的系统性siRNA沉默之后研究转录因子激活。在体内，嵌合小鼠将用于确定TLR4对E.杆菌西北大学泌尿外科系为临床和基础科学家之间的密切合作提供了理想的培训环境，创造了有利于学术生涯发展的环境。 公共卫生相关性：这项拟议的研究将有助于更好地了解许多泌尿系统疾病的机制，包括前列腺炎和良性前列腺增生（BPH），这些疾病影响着数百万男性。

DESCRIPTION (provided by applicant): 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.