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

生物医学研究核心 1 - 生物标志物、生物材料和细胞模型核心

基本信息

批准号：
10059766
负责人：
DARREN P. WALLACE
金额：
$ 22.62万
依托单位：
UNIVERSITY OF KANSAS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-15 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10059766
关键词：
3-Dimensional Age Alcohol consumption Animal Model Autosomal Dominant Polycystic Kidney Beta-N-Acetylglucosaminidase Biocompatible Materials Biological Assay Biological Markers Biomaterials Research Biomedical Research Blood Blood Urea Nitrogen CCL2 gene Caffeine Cell Line Cell Proliferation Cell model Cells Chronic Kidney Failure Clinic Clinical Clinical Research Cohort Studies Collagen Collection Creatinine Cultured Cells Cyst Cyst Fluid Cystic Fibrosis Transmembrane Conductance Regulator DNA Databases Detection Development Diagnosis Disease Duct (organ) structure Early Intervention Epithelial Cell Proliferation Epithelial Cells Epithelial cyst Family Fluids and Secretions Formalin Freezing Gene Mutation Gene Targeting Generations Genes Goals Gold Growth Hospitals Human Immunoassay In Vitro Individual Industry Injury to Kidney Investigation Kansas Kidney Knock-out LCN2 gene Laboratories MRI Scans Measurement Medical History Molecular Monitor Mutation Nephrons Paraffin Embedding Participant Pathogenicity Pathway interactions Patients Pharmaceutical Preparations Plasma Preparation Provider Race Reagent Recording of previous events Research Research Personnel Risk Risk Factors Sampling Serum Services Siblings Site Smoking History System Testing Therapeutic Therapeutic Agents Therapeutic Intervention Time Tissue Embedding Tissues Training Translating Translational Research Translations Universities Urine biomarker discovery biomarker panel cell immortalization cohort comorbidity drug testing effective therapy electrical measurement exosome experimental analysis high resolution imaging human tissue in vitro Assay in vitro Model interstitial cell kidney cell monolayer mutant novel novel therapeutics post gamma-globulins potential biomarker predictive marker rat KIM-1 protein recruit renal damage repository response sex specific biomarkers therapeutic evaluation urinary volunteer

项目摘要

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.

项目摘要-摘要-BRC 1 生物标志物，生物材料和细胞模型核心由四个实验室组成，为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生物标志物实验室保存了来自早期- 在早期PKD观察队列（EPOC）中监测的ADPKD阶段， study.储存库还储存了来自这些ADPKD参与者的高危兄弟姐妹，正常志愿者，以及患有ADPKD的患者，他们来到堪萨斯大学医院的PKD诊所。的目前缺乏ADPKD的敏感和特异性生物标志物是开发新药物的主要障碍。治疗该核心将协助研究人员发现有效的生物标志物，用于诊断和监测早期ADPKD的进展，这是肾脏可逆性损伤之前的关键时刻。核心还将对临床样本进行内部生物标志物分析，以协助PKD研究者进行评估治疗干预措施。PKD生物材料实验室维护一个已建立的广泛的人类ADPKD生物标本，包括固定和冷冻的囊性组织、囊液和原代培养的囊肿上皮细胞。核心对于向以下人员提供ADPKD生物标本至关重要：过去14年的学术和行业调查。PKD细胞模型实验室协助研究人员在使用人原代ADPKD细胞、正常人肾（NHK）细胞和永生化的肾细胞系在小心控制的体外试验。核心在体外模型方面拥有相当丰富的专业知识用于研究参与囊肿上皮细胞增殖、CFTR依赖性Cl-和液体分泌和体外包囊形成。核心小组将继续向调查人员提供以下方面的服务和培训： PKD细胞模型，用于研究囊肿生长机制和评估潜在的治疗化合物. PKD基因靶向实验室通过基因- 编辑并协助核心用户进行基因靶向方法，以测试特定的假设。核心将介绍来自人类集合管的永生化细胞中PKD 1或PKD 2的特异性突变，集合管是囊肿的主要部位 ADPKD的形成。这使得研究人员能够使用以下方法来检查细胞对PKD突变的反应：等基因正常和PKD突变细胞系。PKD生物标志物、生物材料和细胞的总体目标模型核心是提供人类ADPKD生物标本和细胞模型，以帮助研究者翻译研究