Cai, Dongsheng , MD
Central mechanism of obesity-related hypertension via IKK-beta/NF-kappaB pathway
General Research Subject: Both Type 1 And Type 2 Diabetes
Type of Grant: Basic Science
Project Start Date: January 1, 2012
Project End Date: December 31, 2014
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
Our research project in studying the mechanisms of obesity and hypertension can significantly contribute to treatment and prevention of diabetes from multiple aspects. First, from the disease etiology and pathogenesis perspective, both obesity and obesity-related hypertension are core components of the so-called Metabolic Syndrome, which is the most often pathogenic mediator of diabetes. Thus, elucidating the pathogenic mechanisms of obesity and related hypertension will help prevent or treat Metabolic Syndromes to counteract the development of obesity-related diabetes. Second, by understanding the some common brain inflammatory pathways in obesity, pre-diabetes and cardiovascular disorders, it may provide a root target for breaking the disease network which underlies the development of diabetes. Third, from the disease prognosis perspective, cardiovascular disease is a major diabetic complication and a leading cause for diabetic mortality. To this end, studying the molecular and cellular pathogenic mechanisms of obesity and related hypertension will help reverse or prevent the development of diabetes-related cardiovascular complications and thus greatly reduce diabetes mortality.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
Type 2 diabetes and obesity-related hypertension share the common etiologic factor of obesity. In this background, our studies have revealed that these two diseases share a common brain pathogenic mechanism related to abnormal activation of brain inflammatory pathway. While more detailed mechanistic studies are under way, our studies have pointed to the potential of controlling brain inflammation to cure or prevent several pre-diabetic changes including obesity-related hypertension. Further, cardiovascular conditions such as hypertension are often the leading causes of diabetic mortality. Findings from our hypertension studies already did and will continue to reveal therapeutic targets to control diabetes-related cardiovascular conditions.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
Endocrine disease and diabetes in particular, has been the theme of my past two decades of academic and scientific pursuit and devotion. Since I was an undergraduate, I was profoundly fascinated by life science and meanwhile deeply concerned of human well-being, which motivated me to study for human medicine. Later my interest specifically developed into the field of endocrine disease, which led me to choose endocrinology as my Ph.D. major. My early science career was generously supported by the American Diabetes Association, while I was a postdoctoral investigator at the Joslin Diabetes Center of Harvard Medical School, where I made the original discovery of several insulin resistance mediators which contribute to the development of diabetes. Since 2005, I launched my independent research career, where I discovered several brain pathways which cause obesity and obesity-related metabolic changes. More recently, my laboratory has made several high-impact research discoveries regarding the neuroimmune mechanisms of diabetes and diabetes-related metabolic diseases such as hypertension. Winning this prestigious award will undoubtedly tremendously help further the developments of these high-impact research projects and lead to more clinically applicable discoveries.
In what direction do you see the future of diabetes research going?
Generally speaking, a thorough understanding of the disease mechanisms is always top on the priority list. The peripheral mechanisms of diabetes have been well-investigated in the past two decades, while the brain mechanism - which is also fundamental to disease development, is a relatively new concept and has been established only in the past few years. Accordingly, many key questions remain unaddressed in this central aspect and call for more mechanistic studies, particularly regarding the brain regions which regulate whole-body metabolic homeostasis. A second research focus is to translate basic research findings into practical therapeutic and preventive applications. For instance, while brain inflammatory activation critically underlies the development of obesity-related diabetes, how to target brain inflammatory system effectively and selectively in specific brain areas to combat diabetes still has some technical barriers to overcome.
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