ADAR-Mediated RNA Editing in Focal Segmental Glomerulosclerosis
Abstract
Focal Segmental Glomerulosclerosis (FSGS) has been identified as a Topic Area for study under the Peer Reviewed Medical Research Program of the Congressionally Directed Medical Research Programs. The proposed research project addresses specifically the Area of Encouragement related to improving our understanding of the causes of FSGS. FSGS is a disease of the kidneys, in which the structures that filter blood -- the glomeruli -- become damaged, preventing them from fulfilling their normal function. The consequences of reduced filtration include fluid retention, high blood pressure, and ultimately kidney failure. The estimated 100,000 cases of FSGS in the United States are among the most severe and challenging kidney disorders confronting nephrologists. The current treatments for individuals with FSGS are not based on an understanding of the molecular basis for the disease, and in many instances fail to prevent progression to end-stage kidney disease, such that the affected individual requires dialysis or kidney transplantation. Furthermore, transplanted kidneys in these individuals tend not to last as long as those transplanted for other kidney diseases, and FSGS is associated with a greatly increased risk of developing cardiovascular disease. Thus, FSGS takes a huge toll on the quality of life of affected individuals, who may spend several days each week in dialysis units, and consequently of their families as well. Moreover, because the healthcare costs for all individuals suffering from end-stage kidney disease is covered by Medicare, this represents a major public health issue that accounts for tens of millions of dollars in the Federal budget, as well as costs associated with decreased productivity. There is an overwhelming need for developing new pharmaceutical treatments to prevent irreversible damage to kidneys in patients with FSGS. While much research focuses on a better understanding of the underlying pathological mechanisms by identifying additional genes responsible for this disease, my laboratory s approach has been to improve the regenerative capability of the kidney, and thus prevent FSGS. Most recently, we have started to investigate the novel concept that damaged kidneys activate a specific program known as ?RNA editing? by which small changes are introduced into proteins that are important for the maintenance of proper kidney function. RNA editing represents a new and exploding field in biology that has the potential to fundamentally add to our understanding of disease processes. We propose to demonstrate the role of ?RNA editing? pathways in the pathogenesis of FSGS. Demonstration of a major role for RNA editing in the onset and progression of FSGS would provide a basis for development of novel pharmaceutical approaches for this devastating disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710184
Entities
People
- Valerie Schumacher
Organizations
- United States Army