The role of endothelial protein C receptor (EPCR) pathway in diabetic retinopathy

There is an urgent need to identify novel treatments that can prevent progression of diabetic retinopathy and perhaps even repair retinal damage. This project will use state-of-the-art approaches to fully understand a novel receptor protein called “EPCR” and identify new opportunities to prevent retinal blood vessel damage during diabetes.

Currently available treatments for diabetic retinopathy (DR) largely focus on end-stage disease. Fresh perspectives are needed to develop novel and more effective prevention/reversal strategies. One such perspective is targeting the early stages of DR to enhance vessel repair, thereby preventing progression to the sight-threatening end-stages. In this project, a signalling pathway involving Activated Protein C (APC) binding to Endothelial Protein C Receptor (EPCR) will be investigated. Modulation of this pathway could serve to protect retinal endothelial cells from diabetes-induced damage. Furthermore it could enhance the reparative potential of endothelial stem cells in a diabetic environment.

The molecular mechanisms of the APC/EPCR pathway and the potential of APC treatment to overcome diabetes-induced dysfunction will be dissected in cell culture models and in a mouse model of DR. This research will add to our understanding of key pathogenic mechanisms in DR and identify new avenues for much-needed therapies that address early stages of DR and prevent progression to vision-loss.

In this exciting project, the student will have the opportunity to develop a range of research skills including cell biology (including primary cell culture) and molecular biology techniques (e.g. PCR, western plot, flow cytometry, next generation sequencing) as well as working with mouse models.