Redox Biology Program

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John Corbett, PhD

Phone:  414-955-8768
Fax:      414-955-6510

Corbett Laboratory

The Corbett Laboratory, in the Medical College of Wisconsin Department of Biochemistry, is focused on determining the factors that influence the function and survival of pancreatic beta cells in the context of Type 1 and Type 2 diabetes mellitus.

It has three ongoing research programs.

The broad goals of the first project are to elucidate the cellular mechanisms responsible for pancreatic beta cell death and identify mechanisms by which beta cells protect themselves against cytokine- and free radical-mediated damage. Nitric oxide, the primary mediator of the inhibitory actions of interleukin-1 (IL-1) and interferon-g (IFN-g) on beta cell function, also activates a "recovery" pathway that protects beta cells from cytokine-mediated damage. It is the delicate balance between the toxic and protective actions of nitric oxide that ultimately determine the susceptibility of beta cells to cytokine-mediated damage.

The broad goals of the second research program are to elucidate the biochemical mechanisms by which virus infection regulates macrophage activation and to determine the virus-activated pathways that contribute to the loss of beta cell function and viability. Using a virus known to induce diabetes in susceptible mice, we have recently identified three novel antiviral signaling pathways that regulate inflammatory gene expression in macrophages.

The third major research program tests the hypotheses that increased levels of random mutations in beta cell mtDNA lead to the loss of beta cell function and the inability to maintain normal glycemic control, and increase the vulnerability of beta cells to a secondary stress such as insulin resistance induced by a high fat diet. To examine these hypotheses, transgenic (Tg) mice that accumulate mtDNA mutations in beta cells due to the expression of an error-prone mtDNA polymerase under control of the rat insulin promoter have been generated.
© 2014 Medical College of Wisconsin
Page Updated 06/13/2013