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DRC Director's Report - September 2024

FOEDRC faculty, Dr. Samuel Stephens, Associate Professor in the Division of Endocrinology and Metabolism in the Department of Internal Medicine, has been awarded 2 major grants. The first is a three-year, $1.3M R01 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) for his project, “Defining the contribution of mitochondrial redox metabolism to support proinsulin folding in the endoplasmic reticulum.”

The second is a three-year research grant for a total of up to $750,000 entitled “Role of β-cell Golgi dysfunction in Type 1 diabetes pathogenesis”, from Breakthrough T1D (formerly JDRF). For the NIDDK project, Dr. Stephens and his team will be investigating the role of pan-creatic beta cell (β-cell) failure in the transition from insulin resistance to Type 2 diabetes. 

Because defects in the β-cell’s synthesis of insulin are not completely understood, understanding if and how β-cell function could be restored would have significant therapeutic value. “Our observations have identified a new mechanism linking defects in mitochondrial and redox metabolism with the decline of insulin production in Type 2 diabetes,” Stephens said. “Our proposed studies will define the molecular linkages be-tween mitochondrial metabolism and insulin production and address how this process is dismantled early in the development of Type 2 diabetes.” 

Regarding the Breakthrough T1D project, “Our recent studies have uncovered a novel role for immune-derived inflammatory signals in remodeling the β-cell’s surface that may provide critical insight into the beta-cell’s role in Type 1 diabetes development,” Stephens said and that “We propose that inflammatory mediators activate a molecular switch in the β-cell that generates immunogenic signals on the β-cell surface. Our work will define the molecular mechanisms of how inflammatory signals activate this molecular switch and define key changes to the β-cell surface.” 

Notably, both grants build on preliminary work funded by the FOEDRC Pilot & Feasibility grant that Dr. Stephens obtained in 2022, demonstrating a significant return on investment. Congratulations to Dr. Stephens on this milestone! We look forward to celebrating even more of his achievements in the future.

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