Functional role of the renal risk gene WDR37 in renal disease

• Applicant: Professor Dr. E. Wolfgang Kühn
• Subject Area: Nephrology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 443851440

Chronic kidney disease is the tenth leading cause of death worldwide. 10-15 % of the population are affected by chronic kidney disease. Chronic kidney disease causes renal failure in a subset of patients, necessitating kidney transplantation or dialysis. Common causes of chronic kidney disease are diabetes, auto-immune disease, hypertension or inherited syndromes, yet in 30-40 % the cause is unclear. To improve the understanding of the mechanisms underlying kidney diseases, risk genes for decreased renal funcion have been identified in large genetic studies (GWAS). In unrelated investigations of our research group, one of the risk genes was found as an interactor of LKB1. We have previously characterized LKB1 as a key molecule that regulates inflammation and fibrosis (scarring) in the kidney. Since the loss of renal function is invariably associated with fibrosis, we postulate that the protein encoded by the risk gene mentioned above funtionally interacts with the regulatory module surrounding LKB1 to play a role in renal injury and the development of fibrosis. We aim to examine expression of the candidate protein in biopsies of different renal diseases. We will delete the candidate gene in the mouse kidney to study its function in normal kidneys, as well as after injury. We will test if the candidate protein plays a role in adult slowly progressive polycystic kidney disease (ADPKD), where LKB1 has an established role. We will employ cellular systems to define molecular mechanisms of the candidate protein. The proposed investigation will help to elucidate new aspects of the pathogenesis of chronic kidney disease and clarify if the candidate protein is a potential therapeutic target.

• DFG Programme: Research Grants