Despite significant recent advances made in glycemic control, patients with diabetes still suffer from debilitating vascular complications, such as peripheral artery disease (PAD). My long-term research goal is to gain greater insight into the mechanisms of vascular dysfunction in diabetic PAD, and to develop new and improved therapeutic strategies to restore vascular functions. It is toward this goal that I have developed a research plan and a career development plan for this American Heart Association Career Development Award application. Although the detailed mechanisms by which the metabolic milieu in diabetes lead to the development and progression of PAD are still incompletely understood, all mechanisms converge on the vascular endothelium as a common disease target. Endothelial dysfunction is a key marker and a major mediator in diabetic vascular disease. To date, there is no in vitro human disease model that can effectively recapitulate endothelial dysfunction in diabetic PAD. There is also no effective treatment method that could inhibit or reverse the persistent endothelial dysfunction due to metabolic memory. The research plan will address those issues through two specific aims: Aim 1 will focus on the establishment of in vitro disease models for diabetic endothelial dysfunction, using induced pluripotent stem cell-derived endothelial cells as the cell source. These models will serve as the platform to investigate methods to prevent and/or rescue diabetic endothelial dysfunction. Aim 2 will focus on the investigation of potential therapeutic targets to restore endothelial functions in the established in vitro models. This proposal also describes a 3-year career development plan for establishing an independent academic career in diabetic vascular research and bioengineering. I am a newly appointed research assistant professor at Northwestern University with a Ph.D. in biomedical engineering. For the award period, a multi-disciplinary mentorship team has been assembled to provide me with in-depth training in vascular biology, epigenetics and clinical research, to complement my background in biomedical engineering. Overall, this award will advance my long-term career goal, which is to establish an independent research program focused on diabetic vascular research and to ultimately translate my research into clinical use to improve the quality of life for diabetic patients.
|Effective start/end date||4/1/19 → 3/31/22|
- American Heart Association (19CDA34620011)