Professor, Pediatrics
Director , Max McGee National Research Center for Juvenile Diabetes
Medical College of Wisconsin,
8701 Watertown Plank Road,
Milwaukee, WI 53226.

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Research Interests:
– molecular genetics
– the role of innate immunity mechanisms in the development of Type 1 diabetes

The development of complex diseases involves the interplay of multiple genes, cell types and environmental factors. An integrated perspective of how these factors interact is vital towards the dissection and understanding of complex disease as well as a prerequisite for the development of successful treatment and prevention strategies. The main focus of the Hessner Laboratory has been to apply functional genomics to type 1 diabetes (T1D), an autoimmune disease that results in destruction of the pancreatic beta cells and life‐long dependency on exogenous insulin.
We have applied functional genomics to the events leading to T1D in both human subjects and a rat model. We use congenic BioBreeding (BB) rat derivatives. BB DR.lyp/lyp rats are spontaneously diabetic due to a mutation in the Gimap5 gene, rendering them deficient in regulatory T cells. In contrast, DR.+/+ rats possess an intact Gimap5 gene and do not develop spontaneous T1D, but become diabetic upon depletion of regulatory T cells. T1D in BB rats also involves cytotoxic T cells, since their depletion abrogates disease. Through expression profiling of pancreatic lymph nodes (PLN) and isolated PLN subpopulations, we identified a key role for mast cells in BB rat diabetogenesis. We have confirmed their importance by delaying/preventing T1D in BB rats with mast cell inhibiting drugs. Furthermore, unlike the control strains, we find the congenic BB strains predisposed to T1D in that their pancreatic ß cells begin expressing mast cell recruiting cytokines early in life. In addition to employing genomic, histological, immunological, and bioinformatic strategies, we are undertaking projects in collaboration with the laboratories of Drs Jacob and Geurts that use Zinc Finger nuclease technology to generate targeted gene knockouts as well as transposon-mediated transgenesis, to genetically dissect the inflammatory process that underlies T1D in the BB rat.