Xu, Jian , PhD
The role of eNOS-derived nitric oxide in the regulation of 26S proteasome functionality in diabetes
General Research Subject: Both Type 1 And Type 2 Diabetes
Focus: Complications\ Macrovascular-Atherosclerotic CVD and Human Diabetes, Complications\Macrovascular-Cellular Mechanisms of Atherogenesis in Diabetes
Type of Grant: Junior Faculty
Project Start Date: January 1, 2012
Project End Date: December 31, 2014
Vascular homeostasis is the ability of a blood vessel to maintain its internal equilibrium. Loss of this ability is a major cause of diabetic morbidity and mortality, and treatments that restore or prevent such a loss would be of immense value to diabetic patients. However, the processes causing the loss are poorly understood, and effective treatments are not available. Two observations suggest a way of solving this problem. First, the gaseous molecule nitric oxide generated by a blood vessel is known to be important for maintaining the internal equilibrium of the vessel. Second, uncontrolled protein chopping machinery in diabetic animal model is linked to the loss of vessel equilibrium. It is not clear how diabetes affects the chopping machine; however, preliminary data suggest that the gaseous molecule may be an internal controller of the chopping machine. When the blood vessel cannot produce enough of this gaseous molecule, as it is the case of diabetes, the chopping machine loses its control. The goals of the proposal are to test if such a connection exists and if that can be controlled. This will be tested in a diabetic mouse model, which has been equipped with a functional monitor specific for the chopping machine, one the most innovative aspects of the proposal. If the connection proves to be working, new and even better drugs can be designed to improve the internal equilibrium of the blood vessel in diabetes.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and or/curing diabetes?
Vascular homeostasis is the ability of a blood vessel to maintain its internal equilibrium. Loss of this ability is a major cause of diabetic morbidity and mortality, and treatments that restore or prevent such a loss would be of immense value to diabetic patients. However, the processes causing the loss are poorly understood, and effective treatments are not available. My project covers diabetic complications: the understanding of how vascular homeostasis gets lost in diabetes in the first place. The project seeks to link the availability of an endogenous factor to protein chopping machine which is essential to the stability of vascular protective proteins. If the connection proves to be true, new and even better drugs can be designed to improve the internal equilibrium of diabetic vasculature.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
My project will help to identify mechanisms of why and how diabetes impairs vascular homeostasis. The findings will facilitate the development of more or even better therapy in the future so that loss of vascular homeostasis could be treated earlier and ultimately cured.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
I have had a long-standing interest in and passion for biomedical research, because I strongly believe that biomedical research can make the difference in fighting diabetes, an unmet medical need. The highest goal of my career is to lead an edge-cutting lab to perform researches aiming to understand mechanisms underlying diabetes and its vascular complications for a cure. The award provides a critical means for me reaching to the next levels of my career goal.
In what direction do you see the future of diabetes research going?
Future of diabetes research will witness multidisciplinary approaches in understanding complex disease processes in order to find a cure for diabetes and its complications."
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