Biliary Atresia Clinical Research Consortium: Pittsburgh

描述（由申请人提供）： 在本申请中，我们建议在匹兹堡儿童医院（CHP）建立一个临床中心，作为NIDDK赞助的胆道闭锁临床研究联盟的一部分。CHP是宾夕法尼亚州西部唯一的三级儿科医疗中心，二十多年来在儿童肝移植的发展中发挥了先驱作用。在过去的五年里，该计划已经照顾了60多名胆道闭锁（BA）患者和125多名新生儿肝炎患者。该提案将利用NIH资助的CHP儿科G-CRC、Starzl移植研究所、匹兹堡大学（皮特）医学院临床研究办公室的可用资源，以及广泛的专业知识进行合作。皮特公共卫生学院内的临床研究项目。我们将研究的假设，BA是几个潜在的疾病的表型，提出了一个大规模的数据库，以确定在一个严格的特征人口BA患者的亚组。其次，我们提出了一个短期项目，以筛选突变的人类inv基因的人类直系同源物在一个亚组的BA患者谁也有异常的内脏器官situs确定。该项目有可能确定肝胆系统异常形态发生的遗传机制和BA患者亚组的诊断标志物。第三，我们提出了一个长期的项目，使用基因芯片分析几种新的模型系统，以确定肝脏基因的表达是专门改变BA。这第三个项目的目的是确定新的诊断和/或预后标志物，并提供进一步的基础研究BA的病理生物学的线索。

DESCRIPTION (provided by applicant): In this application we propose the development at Children's Hospital of Pittsburgh (CHP) of a Clinical Center as a part of the NIDDK-sponsored Biliary Atresia Clinical Research Consortium. CHP is the only tertiary pediatric medical center in Western Pennsylvania and has played a pioneering role in the development of liver transplantation for children for well over two decades. The program has cared for more than 60 patients with biliary atresia (BA) and more than 125 patients with neonatal hepatitis over the last five years. The proposal will utilize the resources available from the NIH-funded Pediatric G-CRC at CHP, the Starzl Transplantation Institute, the Office of Clinical Research within the School of Medicine of the University of Pittsburgh (Pitt), as well as, the extensive expertise for conducting collaborative clinical research programs within the School of Public Health at Pitt. We will examine the hypothesis that BA is the phenotype of several underlying disorders by proposing a large-scale database to identify subgroups within a rigorously characterized population of BA patients. Second, we propose a short-term project to screen for mutations in the human orthologue of the human inv gene in a subgroup of patients with BA who also have anomalies of visceral organ situs determination. This project has the potential to identify a genetic mechanism for abnormal morphogenesis of the hepatobiliary system and a diagnostic marker for a subgroup of BA patients. Third, we propose a longer-term project using gene chip analysis of several novel model systems to identify hepatic genes for which expression is specifically altered in BA. This third project is designed to identify new diagnostic and/or prognostic markers and to provide leads for further basic research on the pathobiology of BA.