George M. O'Brien Kidney Center at Yale

中心项目摘要/摘要这是一份乔治M.奥布莱恩肾脏中心 在耶鲁。该中心的建立与总体目标，以促进基础，翻译和临床 研究将促进肾脏疾病的预防和治疗。重点研究领域 是上皮细胞生物学和肾生理学;遗传性肾病和肾脏发育;急性肾 损伤（阿基）和慢性肾病（CKD）;以及血管生物学、炎症和肾小球疾病。一 该中心的一个至关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 他们可以获得高度专业化的服务，而这些服务通常是无法获得的，无法支持他们的研究。本 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 (Core 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。其服务包括麻醉动物的清除研究，组织学灌注固定 研究、血清和尿液电解质值、酸碱参数、血清和尿液肌酐、平衡研究 在代谢笼中，麻醉小鼠的急性血压测量和慢性清醒血液 通过无线电遥测进行压力测量。疾病模型和机制核心（核心B）提供了 用户可以随时访问独特的小鼠模型、相关的细胞系资源和先进的人类 转化技术其服务包括细菌人工染色体（BAC）重组工程和 转基因，支持CRISPR/Cas9基因组编辑用于小鼠系生产，支持肾细胞系 通过基因组编辑或从突变小鼠产生，并支持基于靶向蛋白质的询问， 人类尿液和肾脏活检样本。人类遗传学和临床研究核心（Core C） 服务和培训，以加强肾脏疾病的转化研究。最初是为了促进 遗传学研究，其服务包括患者DNA提取和存档，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。它的服务已经扩大到现在促进翻译研究超越 遗传学，包括支持方案制定、患者招募、样本处理、生物库， 生物标志物的多重测定以及生物统计学和流行病学支持。我们的核心目前有一个 调查员的合并用户群>145人，包括外部机构的>90人。试点和可行性方案 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，并促进与肾脏直接相关的转化和临床研究 疾病此外，丰富计划通过最大限度地提高相互作用来加强肾脏疾病研究 以及肾脏研究者和受训者之间的信息共享，并通过提供活动， 招聘和教育从本科生到博士后研究员的各级培训人员。

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.