Determine Drug-Gene and Drug-Drug Interaction Using a Zebrafish Polycystic Kidney Disease Model
Abstract
Topic Area: Polycystic Kidney Disease Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease affecting more than 600,000 Americans and an estimated 12.5 million people worldwide. Genetic studies revealed that mutations in either PKD1 or PKD2 are responsible for ADPKD. The two genes encode two proteins named Polycystin 1 and Polycystin 2, respectively. Past research suggests that the two proteins function together. It is also known that a cell surface finger-like structure called the cilium plays an important role in ADPKD. In addition to kidney cyst formation, ADPKD patients have increased risk in multiple conditions outside of the kidney, including heart disease and brain aneurysm, highlighting the need of a more holistic approach. Since ADPKD is a slow-progressing disease, it is likely that patients are exposed to a variety of U.S. Food and Drug Administration (FDA)-approved drugs. In addition, some patients are treated with tolvaptan. In this project, we propose to take advantage of the zebrafish model system to systematically evaluate drug-gene and drug-drug interaction in intact animals holistically and across multiple organs. Specifically, we will identify both adverse and beneficial effects of a library of FDA-approved drugs on zebrafish with defective Pkd2. We will also test whether these drugs affect tolvaptan treatment. Results from this project will be informative for selecting proper medicine for routine care of patients with ADPKD and will generate leads for repurposing existing drugs for ADPKD treatment. This project is directly relevant to the Topic Area of Polycystic Kidney Disease. Since the proposal addresses medication toxicity, it is pertinent to the Strategic Goal of Epidemiology.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310020
Entities
People
- Zhaoxia Sun
Organizations
- United States Army
- Yale University