Breakthrough T1D (formerly JDRF) has awarded Samuel Stephens, PhD, associate professor in Endocrinology and Metabolism, a three-year research grant totaling up to $750,000 for the project, Role of β-cell Golgi dysfunction in Type 1 diabetes pathogenesis. Stephens will work with two co-investigators, Ling Yang, PhD, associate professor of Anatomy and Cell Biology, and John Corbett, PhD, Medical College of Wisconsin’s professor and chair of Biochemistry. Stephens and Yang are also members of UI Health Care’s Fraternal Order of Eagles Diabetes Research Center.

Type 1 diabetes (T1D) results from autoimmune destruction of the insulin-producing beta-cells. Although insulin therapies can successfully manage the symptoms of T1D, insulin does not prevent or cure this devastating disease.

“This project stemmed directly from discoveries made by Sandra Blom, a molecular medicine graduate student in the Stephens Lab, who was recently awarded an F31 pre-doctoral fellowship from the National Institute of Diabetes and Digestive and Kidney Diseases to study T1D,” Stephens said.

Emerging evidence highlights the beta-cell as an active participant in disease progression, yet how the beta-cell contributes to its own demise remains a critical gap in the field.

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

The project takes advantage of novel reagents developed by Corbett in collaboration with Rebekah Gundry, PhD, professor and chair of Physiology at the  University of Nebraska Medical Center, via a separate JDRF-funded project to study the beta-cell surface. By leveraging these reagents, the team’s work overcomes a major limitation in the field, and affords the research group a unique opportunity to examine changes in the beta-cell surface that would not otherwise be possible.