Characterization of the prototype inhibitor of CDA1, CHA-061, in diabetic nephropathy in db/db mice

This project seeks to comprehensively characterize our prototype inhibitor of CDA1, CHA-061, for its treatment effect on diabetes associated kidney disease in db/db diabetic mice. The db/db mouse has a mutation in leptin receptor, which leads to obesity and onset of diabetes at the age of 3-4 weeks, with typical features of DN such as albuminuria, renal fibrosis and glomerular sclerotic injury seen at 16-18 weeks of age. This mouse model of diabetes is relevant to the most common form of diabetes seen in clinical practice, type 2 (maturity onset) diabetes. Diabetic db/db and control db/h mice will be treated with the prototype inhibitor, CHA-061, at the age of 8 or 16 weeks for 10 weeks. Relevant renal endpoints of these mice will be analyzed. Dedicated animal technicians are available to assist students with animal handling and caring. Senior researchers and fellow students are also available in the lab to guide and assist with performing a broad range of laboratory experiments. This includes analysis of biological samples involving the use of molecular, biochemical and histological techniques to measure expression levels of specific genes implicated in the functional and structural features of diabetic kidney disease as well as assessing relevant signaling molecules. In vitro studies including the use of cultured cells will also be performed to complement the in vivo findings and to further delineate the molecular mechanisms underlying the action of the inhibitor. Top-up scholarship is available from the department on a competitive basis. You are welcome to discuss the details of the projects and to see how they fit in your specific interests.