Clinical and Translational Core

项目摘要 尽管在常染色体多囊肾新疗法的开发和测试方面取得了新的进展 疾病(ADPKD)，还需要更多的翻译和临床研究来更好地阐明 研究疾病进展的机制，并找出有前景的新疗法。马里兰州的总体目标是 PKD研究和翻译中心临床和翻译核心将创建一个强大的平台 支持人类ADPKD的临床和翻译研究，通过全面的表型 ADPKD患者链接到完整的生物库，包括人体组织样本和细胞培养，以及 前瞻性地确定与PKD相关的结果。我们建议发展： 1)对N=200名ADPKD患者进行综合表型的前瞻性观察研究 到一个强大的标本生物储存库，以及基于血浆和尿液的定向生物标记物 全外显子组测序的测量和深度基因分型。 2)与我们的细胞培养和工程核心合作建立人类ADPKD人类组织库， 包括肾切除标本，囊壁组织标本，囊液，原发和 永生化细胞培养，与临床表型相关。 3)建立ADPKD患者电子登记系统，以促进快速有效地筛选和招募 APKD患者用于临床试验和辅助观察研究。 这些资源将在协作中提升给新的和现有的调查人员并与其共享 与行政核心和库尔德工人党中央协调站点(CCS)合作。我们将进一步与 发现和验证ADPKD严重程度和进展的新生物标志物的研究人员，使用 我们强大的生物仓库和生物标记物实验室设施。

Project Summary Despite recent advances in the development and testing of novel therapies for Autosomal Polycystic Kidney Disease (ADPKD), additional translational and clinical investigations are needed to better elucidate the mechanisms of disease progression and identify promising new therapies. The overall goals of the Maryland PKD Research and Translation Center Clinical and Translational Core are to create a robust platform to support clinical and translational investigation of human ADPKD, through the comprehensive phenotyping of ADPKD patients linked to a complete biorepository including human tissue samples and cell cultures, and prospectively ascertained PKD-related outcomes. We propose to develop: 1) A prospective observational study of N=200 ADPKD patients with comprehensive phenotyping, linked to a robust specimen biorepository, along with targeted plasma- and urine-based biomarker measurement and deep genotyping with whole exome sequencing. 2) A human ADPKD human tissue bank in collaboration with our Cell Culture and Engineering Core, comprising nephrectomy specimens with cyst-specific tissue samples, cyst fluid, and primary and immortalized cell cultures, linked to clinical phenotyping. 3) An electronic ADPKD patient registry, to promote the rapid and efficient screening and recruitment of APKD patients for clinical trials and ancillary observational studies. These resources will be promoted to and shared with new and established investigators in collaboration with the Administrative Core and the PKD Central Coordinating Site (CCS). We will further collaborate with investigators in the discovery and validation of novel biomarkers of ADPKD severity and progression, using our robust biorepository and biomarker laboratory facilities.