University of Michigan O'Brien Center for Urology Res.

密歇根大学的奥布莱恩泌尿学研究中心旨在解决与泌尿疾病相关的广泛的基础、转化和临床问题。该中心将建立在一个关键质量的泌尿学研究人员，包括一个完善的泌尿学研究计划在密歇根大学。为了实现奥布莱恩中心的目标，五个泌尿外科研究项目已经组装，反映了各种不同的泌尿外科疾病的广泛调查。这种广泛的调查建议，以反映独特的目标，奥布莱恩奖机制，即泌尿外科研究的进步一般。因此，我们所提出的工作范围从儿科到成人泌尿系统疾病，从基础科学到临床研究。在项目1中，Jill Macoska博士将利用cDNA微阵列的专业知识，以及独特的年龄特异性基质和上皮前列腺模型，来鉴定衰老对前列腺细胞的影响所导致的基因表达差异。 基质-上皮相互作用。这些发现将对良性前列腺增生（BPH）的病理生理学产生影响。 在项目2中，John Park博士将使用独特的敲除模型和cDNA微阵列，进一步表征阻塞诱导的集合管细胞中考克斯-2的功能，其基础是阻塞性肾病中考克斯-2表达增加的初步数据。这一发现可能指导梗阻性肾病的治疗发展。在项目3中，马丁·桑达博士将使用 杂交转基因小鼠模型，以表征FAS介导的T细胞死亡作为前列腺特异性T细胞耐受的介导物的作用。这一发现将对良性和恶性前列腺疾病的可能免疫干预产生影响。在项目4中，John Wei博士和John Delancey博士将进行临床研究，以确定尿失禁自然史和结局的干预特异性，生理/解剖和种族决定因素。为此，他们将使用失禁症状指数（ISI），这是一种生物统计学上稳健的，经过验证的，广泛适用的工具，用于测量他们在初步研究中开发的多个领域的失禁。这一发现有助于提高尿失禁有效干预措施的选择和评价。在项目5中，Mark Day博士将建立在涉及Rb和雄激素受体（AR）相互作用调节前列腺生长的初步数据的基础上，以表征Rb/E2 F1如何在体外和体内调节AR的转录和活性。这些发现与前列腺生长和BPH有关。这5个项目将得到发展奖励计划的补充，该计划将进一步扩大该奥布莱恩中心的范围，包括不孕症和泌尿流行病学等领域的新研究人员。项目之间的互动将由arl管理核心促进，该管理核心将以多学科中心咨询委员会的形式提供科学监督，并以具有eDNA阵列分析和临床前和临床模型标准分析专业知识的生物统计学家的形式提供生物统计支持。密歇根大学奥布莱恩中心通过涵盖从临床到基础科学，从儿科到成人泌尿学的广泛研究，致力于以广泛而共同的泌尿学研究主题为中心的进步，这是由奥布莱恩泌尿学中心资助机制唯一定义的。

The O'Brien Urology Research Center at the University of Michigan aims to address a broad range of basic, translational, and clinical concerns relevant to urological diseases. The center will build on a critical mass of urology investigators that comprise a well-established urology research program at the University of Michigan. Toward the O'Brien Center objective, five urology research projects have been assembled that reflect a wide range of investigation across various, different urological diseases. This broad spectrum of investigation is proposed to reflect the unique objective of the O'Brien Award mechanism, that being the advancement of urology research in general. The breadth of our proposed work thus spans from pediatric to adult urological diseases, and from basic science to clinical research. In Project 1, Dr. Jill Macoska will use cDNA microarray expertise, and a unique age-specific stromal and epithelial prostate model, to identify gene expression differences consequent to effects of aging on stromal-epithelial interaction. The findings will have implications for the pathophysiology of benign prostatic hyperplasia (BPH). In Project 2, Dr. John Park will use unique knockout models and cDNA microarrays to further characterize obstruction-induced COX-2 function in collecting duct cells, based on preliminary data implicating increased COX-2 expression in obstructive nephropathy. The findings may guide therapy development for obstructive nephropathy. In Project 3, Dr. Martin Sanda will use hybrid transgenic mouse models to characterize the role of FAS-mediated T cell death as a mediator of prostate-specific T cell tolerance. The findings will have implications for possible immune intervention in benign and malignant prostate diseases. In Project 4, Dr. John Wei and Dr. John Delancey will conduct clinical studies to identify intervention-specific, physiological/anatomic and racial determinants of urinary incontinence natural history and outcome. For this purpose they will use the Incontinence Symptom Index (ISI), a biometrically robust, validated, and broadly applicable instrument for measuring incontinence in multiple domains that they developed in preliminary studies. The findings should improve selection and evaluation of effective interventions for urinary incontinence. In Project 5, Dr. Mark Day will build on preliminary data implicating Rb and androgen receptor (AR) interaction in the regulation of prostate growth to characterize how Rb/E2F1 regulates AR trasncription and activity in vitro and in vivo. The findings have relevance to prostate growth and BPH. These 5 projects will be complemented by a Developmental Award Program that will further broaden the scope of this O'Brien Center to include new investigators in areas such as infertility and urological epidemiology, among others. Interaction between Projects will be facilitated by arl Administrative Core that will provide scientific oversight in the form of a multidisciplinary Center Advisory Board as well as biostatistical support in the form of biostatisticians with expertise in eDNA array analysis and in standard analyses for preclinical and clinical models. By embracing a broad range of urology investigation that spans from clinical to basic science, from pediatric to adult urology concerns, the University of Michigan O'Brien Center aims at advances centered on the broad yet common theme of urological research, as uniquely defined by the O'Brien Urology Centers funding mechanism.