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：
10686060
负责人：
DARREN P. WALLACE
金额：
$ 19.95万
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/10686060
关键词：
3-Dimensional Age Alcohol consumption 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 Collagen Collection Creatinine Cyst Cyst Fluid Cystic Fibrosis Transmembrane Conductance Regulator DNA Databases Development Diagnosis Disease Duct (organ) structure Early Diagnosis Early Intervention Epithelial Cell Proliferation Epithelial Cells Epithelial cyst Family Fluids and Secretions Formalin Freezing Gene Mutation Gene Targeting Generations Genes Goals 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 model organism monolayer mutant novel novel therapeutics observational cohort study post gamma-globulins potential biomarker predictive marker rat KIM-1 protein recruit renal damage repository response sex specific biomarkers therapeutic evaluation treatment response 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提供的实验室组成对内部和外部核心用户重视人类的生物测量和核心服务。 PKD生物标志物实验室保留来自患有早期患者的血清，等离子体，尿液和尿外泌体的存储库在PKD早期观察队列（EPOC）中监测的ADPKD，这是一种纵向临床学习。该存储库还从这些ADPKD参与者，正常志愿者，正常志愿者的兄弟姐妹的样本中库存样本以及已建立的ADPKD的患者来到堪萨斯大学医院的PKD诊所。这当前缺乏对ADPKD的敏感和特定的生物标志物是新的发展疗法。核心将协助研究人员发现有效的诊断生物标志物和监视早期ADPKD的进展，这是对孩子造成可逆损害的关键时刻。核心还将对诊所样本进行内部生物标志物分析，以协助PKD研究者理论干预措施的评估。 PKD生物材料实验室保留了一个已建立的存储库人类ADPKD生物测量广泛，包括固定和冷冻的囊性组织，囊肿液和囊肿上皮细胞的一级培养。核心对于提供ADPKD生物测量至关重要在过去的14年中，学术和行业研究人员。 PKD细胞模型实验室有助于研究人员使用人类原发性ADPKD细胞，正常人肾（NHK）细胞和永生经过精心控制的体外测定中的肾细胞系。核心考虑了体外模型的专业知识为了投资涉及囊肿上皮细胞增殖的途径，CFTR依赖性CL和流体分泌和体外囊肿形成。核心将继续向调查人员提供服务和培训 PKD细胞模型研究囊肿生长的机制和评估潜在治疗化合物。靶向实验室的PKD基因有助于通过基因生成新的PKD试剂编辑和协助核心用户采用基因靶向方法来检验特定假设。核心将介绍来自人类收集管的永生细胞中PKD1或PKD2的特异性突变，囊肿的突出部位 ADPKD中的形成。这使研究人员能够使用使用PKD突变的细胞反应等源性正常和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生物测量和细胞模型，以协助研究人员翻译研究。