Research Database
the role of Nogo-B in MAM remodeling mediated endothelial metabolism and angiogenesis in diabetes
Dan Shan, MD, PhD
Institution:
Temple University
Grant Number:
11-23-PDF-47
Type of Grant:
Basic
Diabetes Type:
Type 2 Diabetes
Therapeutic Goal:
Prevent Diabetes
Project Date:
-
Project Status:
active

Research Description

Diabetes is common. Approximately 37.3 million people in the United States have diabetes, which is about 11% of the population. Patients with diabetes have high blood sugar. High blood sugar can cause the cells lining blood vessels (called endothelial cells) to not function. Dysfunctional endothelial cells impair new vessel growth and lessen organ blood supply. This process results in critical chronic diabetic pathologies with severe clinical consequences, including ischemic peripheral arterial disease and long-lasting non-healing wounds. There are currently no fully effective treatments to repair ischemic peripheral arterial disease caused by diabetes. This study proposes that endothelial cells change their nature when subjected to a high-glucose environment caused by diabetes. Endothelial cells will continue to grow but can no longer function properly. Our data shows that genetic changes in blood glucose levels induce endothelial cell functional and structural abnormalities. This study aims to define the underlying causes of this process to identify therapeutic targets and develop a targeted strategy for reversing blood vessel abnormalities. This work will contribute to a better understanding of endothelial cell function in a diabetic environment. More importantly, it may lead to the development of new treatments that can help patients recover from diabetes.

Research Profile

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?

Diabetes mellitus has a high and unremittingly increasing prevalence of 11.3% of the US population and globally. The endothelium maintains vascular tone, structure, and homeostasis in healthy individuals. In contrast, hyperglycemia-induced endothelial cell (EC) dysfunction and dysregulated angiogenesis result in critical chronic diabetic pathologies with severe clinical consequences, including ischemic peripheral arterial disease (PAD) and long-lasting non-healing wounds. The central goal of this study is to delineate the molecular mechanisms of metabolic regulation in EC under homeostatic and hyperglycemia conditions. By uncovering these mechanisms, one may identify drugable targets to improve EC function and manage diabetic PAD and wound healing.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

Diabetes is common. Approximately 37.3 million people in the United States have diabetes, which is about 11% of the population. Patients with diabetes have high blood sugar. High blood sugar can cause the cells lining blood vessels (called endothelial cells) to not function. Dysfunctional blood vessels impair new vessel growth and lessen organ blood supply. This process results in critical chronic diabetic pathologies with severe clinical consequences, including ischemic peripheral arterial disease and long-lasting non-healing wounds. There are currently no fully effective treatments to repair ischemic peripheral arterial disease caused by diabetes. This study proposes that endothelial cells change their nature when subjected to a high-glucose environment caused by diabetes. This work will contribute to a better understanding of endothelial cell function in a diabetic environment. More importantly, it may lead to the development of new treatments that can help patients recover from diabetes.

Why important for you, personally, to become involved in diabetes research? What role will this award play?

My long-term career goal is to develop an independent academic career devoted to a better understanding of the molecular pathogenesis of vascular diseases, and ultimately designing effective therapeutic strategies for their treatment and prevention in the future. As a postdoctoral fellow, my current research focused on determining the molecular mechanisms underlying a reticulon family protein (Nogo-B) in regulating EC functions and angiogenesis in diabetes. I’m investigating how the reticulon protein controls EC functions and angiogenesis in diabetes. A better understanding of the mechanisms underlying angiogenesis in diabetes may shed light on developing new strategies for treating diabetes diseases. My research experiences and the academic courses I have taken not only broaden my view of the med-biological field but also shape my primary interests in the area. Diabetes and its associated cardiovascular diseases are a class of heart or blood vessel diseases that are considered to be the leading cause of death globally. I dream of saving the patients who are afflicted with the diseases. The proposed research builds logically on my prior work. Furthermore, my mentor, Dr. Jun Yu has a broad background in vascular surgery and vascular biology, with specific training and expertise in key research areas of endothelium and monocyte/macrophage biology. With Dr. Yu’s guidance and my previous theoretical and practical experience in research, I am confident that I can successfully accomplish the proposed project. The ADA postdoctoral fellowship will not only provide a unique opportunity for my research in the diabetic field but also further boost my career toward independence.

In what direction do you see the future of diabetes research going?

I believe that diabetes research should be prioritized in line with the mission of the American Diabetes Association to prevent and cure diabetes and to improve the lives of all people affected by diabetes. There is a significant gap between clinical pathology and wet lab research. A better understanding of the pathological and molecular changes in different organs of diabetic patients is an urgent need for future diabetes research.