UAB Childhood Cystic Kidney Disease Core Center (UAB-CCKDCC) - In Vivo Bioassay and Model Development Resource

UAB 儿童囊性肾病核心中心 (UAB-CCKDCC) - 体内生物测定和模型开发资源

• 批准号: 10218164
• 负责人: Bradley K. Yoder
• 金额: $ 16.25万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-20 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10218164
• 关键词: Address; Affect; Alleles; Animal Disease Models; Animal Model; Animals; Autosomal Dominant Polycystic Kidney; Autosomal Recessive Polycystic Kidney; Bardet-Biedl Syndrome; Basic Science; Biocompatible Materials; Biological; Biosensor; Cell model; Cells; Childhood; Cilia; Clinical; Clinical Data; Clinical Trials; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Complement; Cyclic AMP; Cyst; Cystic Kidney Diseases; Cystic kidney; Data; Defect; Development; Disease; Disease Pathway; Disease model; Engineering; FRAP1 gene; Functional disorder; Future; Generations; Genes; Genetic Models; Growth; Home; Human; Human Engineering; In Vitro; Individual; Institution; Kidney; Kidney Diseases; Measures; Meckel-Gruber syndrome; Missense Mutation; Mission; Modeling; Morphology; Mus; Mutation; National Institute of Diabetes and Digestive and Kidney Diseases; Nephronophthisis; Organism; Outcome; Pathogenesis; Pathogenicity; Pathology; Pathway interactions; Patients; Pharmaceutical Preparations; Pilot Projects; Polycystic Kidney Diseases; Proteins; Rattus; Reagent; Reporter; Reproducibility; Research; Research Activity; Research Personnel; Resource Development; Resources; STAT3 gene; Sampling; Sensory; Services; Ships; Signal Pathway; Signal Transduction; Site; Standardization; Syndrome; System; Tail; Testing; Therapeutic; Training; Translational Research; Uncertainty; Vision; Work; base; biobank; cost effective; data repository; effective therapy; effectiveness evaluation; efficacy evaluation; improved; in vitro Bioassay; in vivo; in vivo Bioassay; in vivo imaging; innovation; intravital imaging; macrophage; member; model development; multidisciplinary; mutant; novel; novel therapeutics; pre-clinical; protein function; protein purification; response; screening; serial imaging; therapeutic development; therapeutic evaluation; treatment strategy

ABSTRACT (CORE C) The primary mission of the UAB-Childhood Cystic Kidney Disease Core Center (UAB-CCKDCC) is to work with the PKD Consortium, under the direction of the U24 Central Coordinating Site (U24-CCS) and NIDDK, to eliminate obstacles in cystic kidney disease research that are slowing progress toward the development of improved treatment strategies. The UAB-CCKDCC has assembled a multidisciplinary team of researchers that direct four tightly integrated resource and service-oriented Cores along with an Administrative Core. The collective mission of these Cores is to support, accelerate, and expand basic and translational research by PKD Consortium members by providing access to clinical data and biomaterial from CCKD patients, through the development and distribution of patient-relevant cell and animal models of CCKD to analyze pathogenic mechanisms involved in cyst initiation and progression, and through the development of streamlined, cost- effective pipelines for the PKD Consortium to rapidly ascertain the efficacy of new drugs to slow cyst growth. The In Vivo Bioassay and Model Development Resource (Core C) within the UAB-CCKDCC is tasked with generating and distributing animal models, in vivo biosensors and reporter systems for CCKD associated pathways, and biological reagents generated from these models. Models to be developed include biosensors and reporters in multiple organisms needed to study signaling pathways involved in CCKD and animal models for a wide range of CCKD syndromes with human patient mutations that will be generated based on data obtained in Core A in the UAB-CCKDCC and from the overall PKD Consortium. Core C will also maintain a bank of biomaterials from these models for distribution to promote pilot studies to rapidly test new hypotheses. Finally, the wide spectrum of CCKD and reporter systems generated and maintained by Core C will be made readily available to PKD Consortium for preclinical trails being conducted in Core D of the UAB-CCKDCC to evaluate candidate therapies using highly standardized, cost-effective, and longitudinal imaging and innovative analysis strategies. The services and resources being made available by Core C and it’s integration with the other Cores in the UAB-CCKDCC will expand research activities beyond what is capable in most individual labs and will accelerate research into possible cures by providing for high quality, robust, and reproducible outcomes that are critically needed to prioritize drugs for future clinical trials to halt PKD and other cystic kidney disorders.

摘要（核心 C） UAB-儿童囊性肾病核心中心 (UAB-CCKDCC) 的主要任务是与 PKD 联盟在 U24 中央协调站点 (U24-CCS) 和 NIDDK 的指导下， 消除囊性肾病研究中阻碍开发进展的障碍 UAB-CCKDCC 组建了一个多学科研究团队，以改进治疗策略。 指挥四个紧密集成的资源和面向服务的核心以及一个管理核心。 这些核心的集体使命是支持、加速和扩大 PKD 的基础研究和转化研究 联盟成员通过提供 CCKD 患者的临床数据和生物材料 开发和分发 CCKD 患者相关细胞和动物模型以分析致病性 参与囊肿发生和进展的机制，并通过开发简化的、成本低廉的 为 PKD 联盟提供有效的管道，以快速确定新药减缓囊肿生长的功效。 UAB-CCKDCC 内的体内生物测定和模型开发资源（核心 C）的任务是 生成和分发 CCKD 相关动物模型、体内生物传感器和报告系统 途径以及从这些模型生成的生物试剂包括生物传感器。 并在研究 CCKD 和动物模型中涉及的信号通路所需的多种生物体中产生 针对各种具有人类患者突变的 CCKD 综合征，这些突变将根据数据生成 UAB-CCKDCC 的核心 A 和整个 PKD 联盟的核心 C 也将维持一个银行。 从这些模型中收集生物材料进行分发，以促进试点研究，以快速测试新的假设。 由Core C生成和维护的广泛的CCKD和报告系统将很容易制作 可供 PKD 联盟在 UAB-CCKDCC 核心 D 中进行的临床前试验进行评估 使用高度标准化、具有成本效益的纵向成像和创新分析的候选疗法 核心 C 提供的服务和资源及其与其他核心的集成。 UAB-CCKDCC 的研究活动将超出大多数单个实验室的能力范围，并将 通过提供高质量、稳健且可重复的结果来加速对可能的治疗方法的研究 迫切需要优先考虑未来临床试验的药物，以阻止 PKD 和其他囊性肾病。