Biliary Atresia Clinical Research Consortium: Pittsburgh

描述(由申请人提供)： 在这项申请中，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。在过去的五年中，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。该提案将利用美国国立卫生研究院资助的CHP儿科G-CRC、Starzl移植研究所、匹兹堡大学(匹兹堡)医学院临床研究办公室提供的资源，以及在匹兹堡公共卫生学院内开展协作临床研究项目的广泛专业知识。我们将通过提出一个大型数据库来验证BA是几种潜在疾病的表型这一假设，以确定严格表征BA患者群体中的亚组。其次，我们提出了一个短期项目，在BA患者中筛查人类inv基因的人类同源突变，这些患者也有内脏器官位置确定的异常。该项目有可能确定肝胆系统形态发生异常的遗传机制，并成为BA患者亚群的诊断标记。第三，我们提出了一个更长期的项目，利用几个新的模型系统的基因芯片分析来识别在BA中表达特异性改变的肝脏基因。这第三个项目旨在确定新的诊断和/或预后标志物，并为进一步的BA病理生物学基础研究提供线索。

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.