George M. O'Brien Kidney Center at Yale

中心项目摘要/摘要这是乔治·M·奥布莱恩肾中心的续建申请 在耶鲁大学。该中心成立的首要目标是促进基础、转换和临床 将推进肾脏疾病预防和治疗的研究。重点研究的主要领域 有上皮细胞生物学和肾脏生理学；遗传性肾脏疾病和肾脏发育；急性肾脏 损伤(AKI)和慢性肾脏疾病(CKD)；血管生物学、炎症和肾小球疾病。一个 该中心最重要的好处是为耶鲁大学和全国各地的肾脏研究人员提供 有机会获得高度专业化的服务，而不是以其他方式常规地支持他们的研究。对这件事 最后，该中心包括三个生物医学研究核心。动物生理学和表型核心 (核心A)提供评估肾功能和血压调节的专门服务和培训 在小动物身上。它的服务包括麻醉动物的清除研究，组织学的灌流固定 研究，血清和尿液电解值，酸碱参数，血和尿肌酐，平衡研究 在代谢笼中，麻醉小鼠的急性血压测量，以及慢性清醒的血液 用无线电遥测法测量压力。CORE(CORE B)提供的疾病模型和机制 用户可以随时访问独特的鼠标模型、相关的细胞系资源和高级人类 翻译技术。它的服务包括细菌人工染色体(BAC)重组工程和 转基因，支持用于小鼠品系生产的CRISPR/Cas9基因组编辑，支持肾细胞系 通过基因组编辑或从突变小鼠进行生产，并支持基于蛋白质的靶向询问 人体尿液和肾脏活检样本。人类遗传学和临床研究核心(核心C)提供 提供服务和培训，以加强肾脏疾病的翻译研究。最初成立的目的是为了 遗传学研究，其服务包括患者DNA提取和归档，高通量SNP工具 基因分型和DNA测序，遗传连锁和连锁不平衡分析，以及整个外显子组 捕获和测序。它的服务已经扩展到现在促进翻译研究 遗传学，包括支持方案制定、患者招募、样本处理、生物库、 生物标志物的多重分析，以及生物统计学和流行病学支持。我们的核心目前有一个 &gt；145名调查人员的综合用户群，包括外部机构的&gt；90人。一个试点和可行性计划 的目标是为年轻的研究人员提供初始项目资金，吸引新的研究人员进入 肾脏疾病研究领域，促进与肾脏直接相关的翻译和临床研究 疾病。此外，丰富计划通过最大限度地互动来加强肾脏疾病的研究 以及肾脏研究人员和受训人员之间的信息共享，并通过提供活动来加强 招募和教育各级实习生，从本科生到博士后研究员。

Center Project Summary/Abstract This is an application for renewal of the George M. O'Brien Kidney Center at Yale. This center was established with the overarching goal to facilitate basic, translational and clinical research that will advance the prevention and treatment of kidney diseases. Major research areas of emphasis are epithelial cell biology and renal physiology; inherited kidney disease and kidney development; acute kidney injury (AKI) and chronic kidney disease (CKD); and vascular biology, inflammation and glomerular disease. A critically important benefit of the Center is to provide renal investigators both at Yale and across the country with access to highly specialized services not otherwise routinely available to support their research. To this end, the Center includes three Biomedical Research Cores. The Animal Physiology and Phenotyping Core (Core A) provides specialized services and training for assessing renal function and blood pressure regulation in small animals. Its services include clearance studies in anesthetized animals, perfusion fixation for histology studies, serum and urine electrolyte values, acid-base parameters, serum and urine creatinine, balance studies in metabolic cages, acute blood pressure measurements in anesthetized mice, and chronic awake blood pressure measurements by radiotelemetry. The Disease Models and Mechanisms Core (Core B) provides users with ready access to unique mouse models, associated cell line resources, and advanced human translational technologies. Its services include bacterial artificial chromosome (BAC) recombineering and transgenesis, support for CRISPR/Cas9 genome editing for mouse line production, support for kidney cell line production by genome editing or from mutant mice, and support for targeted protein-based interrogation of human urine and kidney biopsy samples. The Human Genetics and Clinical Research Core (Core C) provides services and training to enhance translational studies in kidney disease. Initially established to facilitate genetics studies, its services include patient DNA extraction and archiving, tools for high throughput SNP genotyping and DNA sequencing, analysis of genetic linkage and linkage disequilibrium, and whole exome capture and sequencing. Its services have been expanded to now facilitate translational research beyond genetics, including support for protocol development, patient recruitment, sample processing, biobanking, multiplex assays for biomarkers, and biostatistical and epidemiological support. Our cores currently have a combined user base of >145 investigators, including >90 at outside institutions. A Pilot and Feasibility Program has the goals of providing initial project funding for young investigators, attracting new investigators into the field of kidney disease research, and fostering translational and clinical studies directly related to kidney diseases. In addition, an Enrichment Program enhances kidney disease research by maximizing interaction and information sharing among renal investigators and trainees, and by providing activities to enhance recruitment and education of all levels of trainees from undergraduate students to postdoctoral fellows.