Clinical and Translational Core

项目摘要 尽管最近在常染色体多囊肾的新疗法的开发和测试方面取得了进展， 疾病（ADPKD），需要额外的翻译和临床研究，以更好地阐明 研究疾病进展的机制，并确定有前途的新疗法。马里兰州的总体目标 PKD研究和翻译中心临床和翻译核心是创建一个强大的平台， 支持人类ADPKD的临床和转化研究，通过全面的 ADPKD患者与完整的生物储存库（包括人体组织样本和细胞培养物）相关， 前瞻性确定PKD相关结局。我们建议发展： 1)一项在N = 200例具有综合表型的ADPKD患者中进行的前瞻性观察研究， 沿着靶向血浆和尿液生物标志物， 测量和使用全外显子组测序的深度基因分型。 2)与我们的细胞培养和工程核心合作的人类ADPKD人类组织库， 包括具有囊肿特异性组织样品的肾切除标本、囊肿液和原发性和 与临床表型相关的永生化细胞培养物。 3)ADPKD患者电子登记，以促进快速有效的筛查和招募 用于临床试验和辅助观察性研究的APKD患者。 这些资源将通过协作推广给新的和现有的调查人员并与他们共享 与行政核心和PKD中央协调网站（CCS）。我们将进一步与 研究人员在发现和验证ADPKD严重程度和进展的新生物标志物，使用 我们强大的生物储存库和生物标志物实验室设施。

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.