Craft, Clarissa , PhD
Extracellular matrix microfibrils as a target for obesity and diabetes therapies
General Research Subject: Type 2 Diabetes
Focus: Adipocytes, Integrated Physiology, Integrated Physiology\Insulin Resistance, Signal Transduction (Non-Insulin Action), Signal Transduction (Non-Insulin Action)\Transcriptional Regulation
Type of Grant: Junior Faculty
Project Start Date: July 1, 2013
Project End Date: June 30, 2016
Diabetes Type: Type 2 diabetes
Diabetes has rapidly become an epidemic health concern, and unfortunately outpaced the development of a cure or improved treatment options. Drug discovery has focused heavily on target molecules in the cells they are trying to fix. This project will approach therapeutic intervention for diabetes and obesity in a novel manner by targeting the environment surrounding diseased cells. Cells exist in a matrix of molecules (proteins) that organizes the cells into a functional tissue. The proteins of the matrix provide mechanical support to tissues, and control key cellular processes by regulating the biological signals that cells receive from the body or the food we consume. Consequently, disturbances in the matrix translate into cellular dysfunction.
The work of Dr. Clarissa Craft has identified a single molecule within the matrix that when deleted in mice cause obesity and diabetes. This protein molecule is called MAGP1, and can be generated in the lab. Importantly, it was shown that treatment of cells with artificially derived MAGP1 regulates communication pathways within cells that are dysfunctional in individuals with diabetes. This project has two goals: 1) Expand knowledge of how molecules in the matrix can regulate the progression of metabolic diseases like obesity and diabetes, thereby identifying new targets for therapeutic intervention. 2) Continue work to understand how MAGP1 functions and initiate pharmacologic studies with MAGP1-derived molecules, testing their ability to improve metabolic disease in mouse models of obesity and diabetes.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
My research targets individuals who develop Type II diabetes as a consequence of excess adiposity. Diet and exercise are often not effective weight loss strategies in Type II diabetics. The goal of my research is to develop a therapeutic strategy for reducing adiposity and restoring glucose metabolism by increasing energy expenditure in adipose tissue.
If a person with diabetes were to ask you how your project will help them in the future,
how would you respond?
Reducing adiposity improves glucose metabolism, even in Type II diabetics. However, diabetics typically have difficulty with weight loss. My research is focused on developing a diabetes therapy that reduces fat storage by increasing the individuals resting metabolic rate.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
Since 1990 the number of obese individuals has tripled, as a consequence, there has been a similar surge in the number of Type II diabetics. Obesity and diabetes is obviously detrimental to ones health, but can also have significant negative consequences on quality of life and lifespan. This award will provide a platform for my efforts to identify therapeutic targets for both obesity and diabetes.
In what direction do you see the future of diabetes research going?
I think it is pivotal for diabetes research to focus on discovering a therapeutic that will ameliorate or reverse the disease, not just treat the symptoms.
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