Investigating the role of complement receptors in diabetic kidney disease

Chronic kidney disease associated with diabetes, also known as diabetic kidney disease, is the leading cause of kidney failure in many developed countries. It is estimated that 30% of patients with type 1 diabetes mellitus and 40% of patients with type 2 diabetes mellitus will develop diabetic kidney disease. Current treatments for diabetic kidney disease delay, but do not reduce the risk of progression to kidney failure. Therefore, there remains a critical need to identify new therapeutic targets to treat and prevent the development of diabetic kidney disease. Traditionally viewed as an important component of the innate immune system, we have recently identified a novel immunometabolic role the complement system plays in diabetic kidney disease that contributes to renal inflammation and injury. The complement cascade is activated by three distinct pathways, which all result in the formation of complement anaphylatoxin proteins C3a and C5a. C3a and C5a bind to their receptors and elicit many inflammatory and immunomodulatory activities. However, their role in diabetic complications are only starting to be unraveled. This project will investigate the role complement receptors play in mediating renal inflammation and injury in diabetic kidney disease using knockout animals and in vitro cell culture models, and to test novel therapies to inhibit these receptors. Project related methods/skills/technologies: - Immunohistochemistry/Western blotting/qPCR/ELISA - flow cytometry - Imaging - Omics/bioinformatics This work will further our understanding of how complement receptors contribute to diabetic kidney disease and ascertain their suitability as novel therapeutic targets.