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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：
10214614
负责人：
DARREN P. WALLACE
金额：
$ 19.54万
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 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10214614
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 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 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 detection platform 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 – BRC1 生物标志物、生物材料和细胞模型核心由四个实验室组成，提供为内部和外部核心用户提供有价值的人类生物样本和核心服务。 PKD 生物标志物实验室保存着来自患有早期疾病的个体的血清、血浆、尿液和尿液外泌体的储存库。 ADPKD 阶段正在早期 PKD 观察队列 (EPOC) 中进行监测，这是一项纵向临床研究学习。该存储库还存储了这些 ADPKD 参与者的高危兄弟姐妹、正常志愿者、以及来到堪萨斯大学医院 PKD 诊所就诊的 ADPKD 患者。这目前缺乏针对 ADPKD 的敏感和特异性生物标志物是开发新药物的主要障碍疗法。该核心将协助研究人员发现用于诊断和治疗的有效生物标志物。监测早期 ADPKD 的进展，这是肾脏出现可逆性损伤之前的关键时期。该核心还将对临床样本进行内部生物标志物分析，以协助 PKD 研究人员评估治疗干预措施。 PKD 生物材料实验室维护着一个已建立的存储库广泛的人类 ADPKD 生物样本，包括固定和冷冻的囊性组织、囊液和囊肿上皮细胞的原代培养物。该核心对于提供 ADPKD 生物样本至关重要过去 14 年的学术和行业调查员。 PKD 细胞模型实验室提供协助研究人员使用人类原代 ADPKD 细胞、正常人肾 (NHK) 细胞和永生化细胞仔细控制的体外测定中的肾细胞系。核心在体外模型方面拥有丰富的专业知识用于研究涉及囊肿上皮细胞增殖、CFTR 依赖性 Cl- 和液体的途径分泌和体外囊肿形成。核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肿生长机制并评估潜在的治疗效果化合物。 PKD 基因靶向实验室通过基因技术协助生产新型 PKD 试剂。编辑并协助核心用户采用基因靶向方法来测试特定假设。核心将介绍来自人类集合管（囊肿的重要部位）的永生化细胞中 PKD1 或 PKD2 的特异性突变 ADPKD 的形成。这使得研究人员能够使用以下方法检查细胞对 PKD 突变的反应：同基因正常和 PKD 突变细胞系。 PKD 生物标志物、生物材料和细胞的总体目标 Models Core 旨在提供人类 ADPKD 生物样本和细胞模型，以协助研究人员转化研究。