Fingar, Diane , PhD
mTOR complex (mTORC) regulation by site-specific mTOR phosphorylation
General Research Subject: Insulin Resistance Pre Diabetes
Focus: Insulin Action\Signal Transduction, Signal Transduction (Non-Insulin Action)\Cytokines and Apoptosis, Signal Transduction (Non-Insulin Action)\Phosphatases-Kinases
Type of Grant: Basic Science
Project Start Date: January 1, 2012
Project End Date: December 31, 2014
Type II diabetes is a disease characterized by abnormal glucose and lipid metabolism in part due to insulin resistance of peripheral tissues (e.g. adipose; muscle; liver) and failure of the insulin-producing cells in the pancreas to compensate for the insulin resistance. A protein known as mTOR (mammalian target of rapamycin) plays crucial roles in insulin-responsive peripheral tissues to control fundamental cellular processes including cell metabolism, cell growth/size, and cell proliferation. The regulation of mTOR function at the cellular level remains incompletely defined, however. As emerging evidence suggests that dysregulated mTOR signaling contributes to diverse human diseases including insulin resistance and type II diabetes, obesity, and cancer, a thorough understanding of mTOR pathway regulation may facilitate the development of therapeutics to treat mTOR-associated disease states. The overarching goal of this proposal is to elucidate mechanisms that control mTOR signaling in cultured cells via a cellular process known as phosphorylation. Phosphorylation describes the process in which a specific chemical group is attached to a protein to control its function. Specifically, our research goal is to study the regulation of mTOR signaling by two novel pathways that control mTOR phosphorylation state. Our preliminary data suggest roles for mTOR phosphorylation in control of cell survival during energy stress and in immune function, which contributes to metabolic dysfunction when dysregulated.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
The research funded by this ADA project seeks to better understand molecular mechanisms that underlie states of insulin resistance found in patients with type II diabetes and obesity. My lab studies cells in culture to decipher the signaling pathways regulated by the insulin, a hormone critical for the proper regulation of blood glucose levels. This research also seeks to elucidate the poorly understood relationship between inflammation, which is common in obesity, and insulin resistance.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
The long-term goal of our research is to identify novel molecular targets within insulin regulated signaling pathways that could be exploited therapeutically to treat insulin resistance and metabolic syndrome found in type II diabetes and obesity.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
Unfortunately, several members of my family, as well as the son of a good friend, have been diagnosed with either type I or type II diabetes. It is rewarding to know that my research efforts could help them in the future to battle their diabetes. This award will enable my laboratory to elucidate molecular mechanisms that contribute to cellular insulin resistance.
In what direction do you see the future of diabetes research going?
The long-term goal of the basic research performed by my lab is to elucidate mechanisms of insulin signaling and cellular metabolism and to better understand how these processes become subverted in diabetes and obesity, which may enable the development of novel medicines to treat these prevalent diseases.
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