Biomedical Research Core 1 - Biomarkers, Biomaterials, and Cellular Models Core

项目摘要-摘要-BRC1 生物标记物、生物材料和细胞模型核心由四个实验室组成，它们提供 向内部和外部核心用户提供有价值的人类生物标本和核心服务。PKD生物标记物 实验室保存着早期患者的血清、血浆、尿液和尿液外切体的储存库。 在早期PKD观察队列(EPOC)中监测的ADPKD分期，这是一项纵向临床研究 学习。该储存库还储存了这些ADPKD参与者的高危兄弟姐妹的样本，正常志愿者， 以及来堪萨斯大学医院的PKD诊所就诊的ADPKD患者。这个 目前缺乏敏感和特异的ADPKD生物标志物是新的发展的主要障碍 治疗。核心将协助调查人员发现有效的生物标记物来诊断和 监测早期ADPKD的进展，这是肾脏出现可逆性损害之前的关键时间。 该中心还将对临床样本进行内部生物标志物分析，以协助PKD调查人员 治疗干预措施的评估。PKD生物材料实验室维护着一个已建立的 广泛的人类ADPKD生物样本，包括固定和冷冻的囊性组织、囊液和 囊上皮细胞的原代培养。核心一直是提供ADPKD生物样品的关键 学术和行业调查人员在过去的14年里。PKD细胞模型实验室协助 研究人员利用人原代ADPKD细胞、正常人肾脏(NHK)细胞和永生化细胞 肾细胞系在体外进行严格控制的检测。Core在体外模型方面拥有相当多的专业知识 为了研究囊性上皮细胞增殖的途径，CFTR依赖的氯离子和液体 分泌物，并在体外形成包囊。该中心将继续为调查人员提供服务和培训 PKD细胞模型用于研究囊性生长的机制和评估潜在的治疗方法 化合物。PKD基因打靶实验室通过基因打靶来帮助产生新的PKD试剂。 编辑并协助核心用户采用基因定位的方法来测试特定的假设。核心将推出 来自人类集合管的永生化细胞中PKD1或PKD2的特异性突变，这是一个突出的囊性部位 在ADPKD中形成。这使研究人员能够使用以下方法检查细胞对PKD突变的反应 等基因正常和PKD突变细胞系。PKD生物标记物、生物材料和细胞的总体目标 Models的核心是提供人类ADPKD生物标本和细胞模型，以帮助研究人员 翻译研究。

Project Summary – Abstract – BRC1 The Biomarkers, Biomaterials, and Cellular Models Core is comprised of four laboratories that provide valuable human biospecimens and core services to internal and external Core users. The PKD Biomarkers Laboratory maintains a repository of serum, plasma, urine, and urinary exosomes from individuals with early- stage ADPKD that are being monitored in the Early PKD Observational Cohort (EPOC), a longitudinal clinical study. The repository also banks samples from at-risk siblings of these ADPKD participants, normal volunteers, and patients with established ADPKD that come to the PKD clinic at the University of Kansas Hospital. The current lack of sensitive and specific biomarkers for ADPKD is a major impediment in the development of new therapies. The Core will assist investigators in the discovery of effective biomarkers for diagnosing and monitoring the progression of early-stage ADPKD, a critical time before there is reversible damage to the kidneys. The Core will also perform in-house biomarker analysis of clinic samples to assist PKD investigators on the evaluation of therapeutic interventions. The PKD Biomaterials Laboratory maintains an established repository of a broad spectrum of human ADPKD biospecimens, including fixed and frozen cystic tissues, cyst fluids, and primary cultures of cyst epithelial cells. The Core has been critical for providing ADPKD biospecimens to academic and industry investigators for the past 14 years. The PKD Cellular Models Laboratory assists investigators in the use of human primary ADPKD cells, normal human kidney (NHK) cells and immortalized renal cell lines in carefully controlled in vitro assays. The Core has considerable expertise with in vitro models for the investigation of pathways involved in cyst epithelial cell proliferation, CFTR-dependent Cl- and fluid secretion, and in vitro cyst formation. The Core will continue to provide service and training to investigators on PKD cellular models to investigate mechanisms for cyst growth and for evaluating potential therapeutic compounds. The PKD Gene Targeting Laboratory assists in the generation of novel PKD reagents through gene- editing and assists Core users in gene-targeting approaches to test specific hypotheses. The Core will introduce specific mutations in PKD1 or PKD2 in immortalized cells from human collecting ducts, a prominent site for cyst formation in ADPKD. This enables investigators to examine the cellular response to a PKD mutation using isogenic normal and PKD mutant cell lines. The overall goal of the PKD Biomarkers, Biomaterials, and Cellular Models Core is to provide human ADPKD biospecimens and cellular models to assist investigators in translational research.