Shoelson, Steven E., PhD
Interactions Between Metabolism, the Immune System, and the Microbiota in Type 2 Diabetes
General Research Subject: Type 2 Diabetes
Focus: Clinical Therapeutics/New Technology, Clinical Therapeutics/New Technology\Pharmacologic Treatment of Diabetes or its Complications, Immunology, Insulin Action, Insulin Action\Insulin Resistance
Type of Grant: Mentor Based Postdoctoral Fellowship
Project Start Date: July 1, 2012
Project End Date: June 30, 2016
Our studies attempt to determine why weight gain and obesity are unhealthy and promote diabetes and associated heart disease. We have found that inflammation, the body's normal response to infection, is also activated by weight gain and obesity, albeit to lesser degrees than is seen in acute infection. We have therefore realized that insulin resistance, type 2 diabetes and cardiovascular disease have immunological underpinnings not unlike those seen for type 1 diabetes. This discovery has provided us with multiple avenues of attack, both in basic science terms for better understanding and clinically to identify pharmacological routes for reversal.
Additional studies suggest that changes in the bacteria in our intestines may also impact diabetes and metabolism, and furthermore the immune system and intestinal bacteria are closely linked. We have therefore hypothesized that the 3 systems -- metabolism, the immune system, and the bacterial flora -- change synchronously and in response to one another. The mentored fellow will conduct basic and potentially translational/clinical research that helps to address these questions.
Mentor: Steven E. Shoelson, MD, PhD Postdoctoral Fellow: Suzanne Devkota,PhD
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
Our studies attempt to determine why weight gain and obesity are unhealthy and promote diabetes and associated heart disease. We have found that inflammation, the body's normal response to infection, is also activated by weight gain and obesity, albeit to lesser degrees than is seen in acute infection. We have therefore realized that insulin resistance, type 2 diabetes and cardiovascular disease have immunological underpinnings similar to those seen for type 1 diabetes. This discovery has provided us with multiple avenues of attack, both in basic science terms for better understanding and clinically to identify pharmacological routes for reversal.
Studies outlined in this application couple our basic and clinical expertise in a true bench-to-bedside and bedside-to-bench approach. Importantly for patients with diabetes, we evaluating a cheap and safe drug that can be used today in patients with diabetes to test whether "anti-inflammatory" approaches provide improved control. To date the answer is yes. In fact we are currently conducting large, phase 3 clinical trials in (1) patients with diabetes and (2) patients with metabolic syndrome and cardiovascular disease. In one series of more basic studies we are identifying specific cell types that appear to either cause or prevent the onset of type 2 diabetes.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
We are developing new glucose lowering treatments for patients with type 2 diabetes, which also appear to have substantial effects in complications associated with both type 2 and type 1 diabetes. In fact, the preclinical animal data are sufficiently good that we have also initiated larger clinical trials in patients with cardiovascular disease, independent of diabetes. We are very interested in looking at the ability of these new therapeutic avenues to diminish risk for complications in type 1 diabetes as well, including microvascular complications.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
My professional goal over the last >30 years has been to understand the molecular underpinnings of diabetes and its complications, and to use this information to guide the development of better therapies. Studies in the lab including those funded by this award will help to ensure that these aspirations are fulfilled.
In what direction do you see the future of diabetes research going?
I hope to see a continuing increase in translational research as we continue to improve our more basic understanding of the pathophysiology in type 2 diabetes and its complications. We also foresee new studies into the use of our anti-inflammatory approaches to target both microvascular and macrovascular complications in type 1 diabetes. I hope that the ADA helps to sponsor an increasing amount of translational/clinical research.
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