Autosomal Dominant Polycystic kidney disease (ADPKD) is characterized by numerous cysts within the kidneys of afflicted individuals. The cysts formed in ADPKD can greatly enlarge the kidneys while replacing the normal kidney structures, resulting in reduced kidney function and progression to end-stage renal disease that can only be treated by lifelong dialysis or kidney transplants. As a disease that affects 1 in 800~1000 individuals, ADPKD is among the most common genetic disorders. In the United States, there are 600,000 individuals, and worldwide 12.5 million, with PKD [1]. Thus, ADPKD represents a major public health issue, and accounts for hundreds of millions (and perhaps over a billion) of dollars in health care costs, particularly for dialysis treatments and the cost of drgs that prevent transplant rejections, as well as the cost involved of decreased productivity and impaired quality of life of individuals with ADPKD. For all these reasons, it is of great importanc to discover treatments that directly affect the molecular causes of ADPKD, and that will prevent the progression to end- stage renal disease and dialysis or transplantation. Over the past 5 years the Kreidberg laboratory has investigated the role of receptor tyrosine kinase and Wnt signaling in the pathogenesis of ADPKD. Dr. Kreidberg's laboratory has found that Wnt signaling and beta-catenin expression is highly elevated in cyst lining cells in ADPKD. In this grant they propose to extend their studies to understand how b-catenin integrates signals from many pathways to cause the initiation of cyst formation in individuals with ADPKD. By understanding the processes involved in the initiation of cysts, we may identify therapeutic targets that inhibit the initiation or early progression of cysts, before they are clinically detectable.

Public Health Relevance

Polycystic kidney disease (PKD) is a hereditary disease with a high prevalence and without a cure. PKD is characterized by numerous cysts within the kidneys of afflicted individuals. PKD is among the most common genetic disorders. In the United States, there are 600,000 individuals, and worldwide 12.5 million, with PKD. Our studies on PKD have focused on how biochemical signaling is abnormal in cells carrying mutations that cause PKD, and how these abnormal signals result in the initiation of cysts.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK102051-02
Application #
8898793
Study Section
Kidney Molecular Biology and Genitourinary Organ Development (KMBD)
Program Officer
Rasooly, Rebekah S
Project Start
2014-07-28
Project End
2018-04-30
Budget Start
2015-05-01
Budget End
2016-04-30
Support Year
2
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code