Harvard Center of Polycystic Kidney Disease Research

多囊肾病(PKD)是一种常见的遗传性疾病，其特点是 肾内充满液体的包囊，与高发病率和死亡率有关。常染色体显性遗传性PKD (ADPKD)影响大约1：1000人，而常染色体隐性遗传性PKD(ARPKD)见于 大约1：20,000个活产婴儿。包囊形成的分子机制尚不清楚。 主任实验室最近的工作表明，多囊蛋白-1和-2作为受体发挥作用 介导G蛋白和钙信号和机械感觉的通道复合体。导演已经 开发了一些具有人类ADPKD基因的小鼠同源突变的小鼠模型 从这些小鼠突变体和它们的野生型窝胎中产生了细胞系。利用这些优势 和其他在主任实验室开发的试剂，中心的调查人员将探索分子 人类多囊肾病的发病机制。项目1(登克博士)将使用生化、细胞 了解异源三聚体G蛋白在PKD中作用的生物学和遗传学方法。在项目2中，Dr。 Kreidberg将使用细胞和分子生物学的组合方法来了解 钙粘附素和整合素在多囊肾病发病机制中的作用。在项目3中，周博士将使用 生化和细胞生物学方法了解纤维囊藻蛋白/多聚管蛋白(FPC)在 多囊蛋白在PKD中的作用比较；在试点和可行性项目1中，瓦西列夫博士将使用 研究多囊蛋白通道调节的电生理学方法：先导性和可行性 项目2 Bonventre博士将使用细胞生物学和遗传学方法相结合的方法来研究 肾损伤分子-1与PKD上皮细胞向间充质细胞转化这些项目中的每个都将是 由核心设施支持，该设施将提供最新的分子成像支持和 管理核心。

Polycystic kidney disease (PKD) is a common genetic disease that is characterized by the development of fluid filled cysts in the kidney and is associated with high morbidity and mortality. Autosomal dominant PKD (ADPKD) affects approximately 1:1000 individuals, whereas autosomal recessive PKD (ARPKD) is seen in approximately 1:20,000 live births. The molecular mechanisms underlying cyst formation remain unclear. The recent work from the Director's laboratory has shown that polycystin-1 and -2 function as a receptor channel complex that mediates G protein and calcium signaling and mechanosensation. The director has developed a number of mouse models with mutations in the mouse ortholog of the human ADPKD gene and generated cell lines from these mouse mutants and their wild type littermates. Taking advantage of these and other reagents developed in the Director's laboratory, the Center investigators will explore the molecular mechanisms underling human polycystic kidney disease. Project 1 (Dr. Denker) will use biochemical, cell biological and genetic approaches to understand the role of heterotrimeric G proteins in PKD. In Project 2 Dr. Kreidberg will use a combination of cell and molecular bioiogical approaches to understand the role of cadherins and integrins in the pathogenesis of polycystic kidney disease. In Project 3 Dr. Zhou will use biochemical and cell biological approaches to understand the role of fibrocystin/polyductin (FPC) in comparison with the roles of polycystins in PKD; In Pilot and Feasibility Project 1 Dr. Vassilev will use electrophysiological approaches to study the regulation of the polycystin channel; In Pilot and Feasibility Project 2 Dr. Bonventre will use a combination of cell biological and genetic approaches to study the role of kidney injury molecule-1 and epithelial to mesenchyme transition in PKD. Each of these projects will be supported by a Core facility that will provide most up to date support on molecular imaging and an administrative Core.