Martin J. Hessner, PhD
Professor
Director, Max McGee National Research Center for Juvenile Diabetes
Department of Pediatrics
8701 Watertown Plank Rd
Milwaukee, WI 53226
Phone: (414) 456-4496
Fax: (414) 456-6663
Email: mhessner@mcw.edu
Education:
B.S., Carroll College, Waukesha, WI, 1985
Ph.D. University of Wisconsin-Milwaukee, 1990
Research Area:
The role of innate immunity mechanisms in 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. We have recognized the potential of gene expression profiling in systems biology as well as its technical and analytical complexities. Therefore, our laboratory has focused on the development of a robust infrastructure for functional genomics focused on the acquisition of quality data. 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 the nondiabetic Wistar-Furth (WF) rat and congenic BioBreeding (BB) rat derivatives. BB DRlyp/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 WF, we find the congenic BB strains predisposed to T1D in that their pancreatic ß cells begin expressing mast cell recruiting cytokines early in life. These findings suggest that mast cells may not only precipitate islet destruction, but may serve as potential initiators of the adaptive T cell mediated response. Our results are consistent with human and rodent studies implicating mast cells in the initiation and progression of autoimmunity. Our efforts continue to better understand the events leading to T1D by employing genomics, histological, immunological, and bioinformatics strategies to the analysis of the BB rat.
Understanding the active proinflammatory mechanisms at and prior to T1D onset is hindered in humans given that relevant tissues are inaccessible and pancreatic immune responses are dilute and difficult to measure in the periphery by traditional approaches. Thus, our human studies have used a sensitive array based genomics bioassay where the serum of recent onset T1D subjects is used to induce gene expression in healthy peripheral blood mononuclear cells (PBMCs). We find that serum of recent-onset diabetics induce a unique pro-inflammatory gene expression signature that includes numerous innate immunity genes and genes regulated by IL-1ß. The signature is completely distinct from that induced by normal control sera. Remarkably, this molecular signature is evident >5 years prior to T1DM onset and holds value in predicting onset in "at-risk" subjects and as a potential measure in primary and secondary prevention trials.
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here for Dr. Hessner's Faculty Collaboration Database profile page, which includes an up to date listing of his publications.