Harvard Center of Polycystic Kidney Disease Research

哈佛大学多囊肾病研究中心

• 批准号: 7885050
• 负责人: Jing Zhou
• 金额: $ 28.92万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7885050
• 关键词: Harvard; Center; Polycystic; Kidney; Disease

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.

多囊肾病（PKD）是一种常见的遗传性疾病，其特征是发生 肾脏中充满液体的囊肿，与高发病率和死亡率相关。常染色体显性多囊肾 (ADPKD) 影响大约 1:1000 的个体，而常染色体隐性遗传 PKD (ARPKD) 见于 大约 1:20,000 活产。囊肿形成的分子机制仍不清楚。 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 蛋白和钙信号传导以及机械感觉的通道复合体。导演有 开发了许多小鼠模型，其中人类 ADPKD 基因的小鼠直系同源物发生突变，并且 从这些小鼠突变体及其野生型同窝小鼠中产生细胞系。利用这些 以及主任实验室开发的其他试剂，中心研究人员将探索分子 人类多囊肾病的机制。项目1（Dr. Denker）将使用生化、细胞 生物学和遗传学方法来了解异源三聚体 G 蛋白在 PKD 中的作用。在项目 2 中，博士 克雷德伯格将结合使用细胞和分子生物学方法来了解 钙粘蛋白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 生物化学和细胞生物学方法来了解纤维囊肿蛋白/多聚导管蛋白 (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，Vassilev 博士将使用 研究多囊蛋白通道调节的电生理方法；试点及可行性 项目 2 Bonventre 博士将结合使用细胞生物学和遗传学方法来研究 PKD 中的肾损伤分子 1 和上皮间质转化。这些项目中的每一个都将 由核心设施提供支持，该设施将提供分子成像的最新支持和 行政核心。

项目成果

The ciliary transition zone: from morphology and molecules to medicine.

• DOI: 10.1016/j.tcb.2012.02.001
• 发表时间: 2012-04
• 期刊: TRENDS IN CELL BIOLOGY
• 影响因子: 19
• 作者: Czarnecki, Peter G.;Shah, Jagesh V.
• 通讯作者: Shah, Jagesh V.

Systems biology approach to identify transcriptome reprogramming and candidate microRNA targets during the progression of polycystic kidney disease.

• DOI: 10.1186/1752-0509-5-56
• 发表时间: 2011-04-25
• 期刊: BMC systems biology
• 作者: Pandey P;Qin S;Ho J;Zhou J;Kreidberg JA
• 通讯作者: Kreidberg JA

Calcium carbonate phosphate binding ion exchange filtration and accelerated denitrification improve public health standards and combat eutrophication in aquatic ecosystems.

碳酸钙磷酸盐结合离子交换过滤和加速反硝化可提高公共卫生标准并对抗水生生态系统的富营养化。

• DOI: 10.2175/106143005x73884
• 发表时间: 2005
• 期刊: Water environment research : a research publication of the Water Environment Federation
• 作者: Yanamadala,Vijay

Transplantation of cells directly into the kidney of adult zebrafish.

将细胞直接移植到成年斑马鱼的肾脏中。

• DOI: 10.3791/2725
• 发表时间: 2011
• 期刊: Journal of visualized experiments : JoVE
• 作者: Diep,CuongQ;Davidson,AlanJ
• 通讯作者: Davidson,AlanJ

Polycystic kidney disease protein fibrocystin localizes to the mitotic spindle and regulates spindle bipolarity.

多囊肾病蛋白纤维囊肿蛋白定位于有丝分裂纺锤体并调节纺锤体双极性。

• DOI: 10.1093/hmg/ddq233
• 发表时间: 2010
• 期刊: Human molecular genetics
• 影响因子: 3.5
• 作者: Zhang,Jingjing;Wu,Maoqing;Wang,Shixuan;Shah,JageshV;Wilson,PatriciaD;Zhou,Jing
• 通讯作者: Zhou,Jing