Primary Area of Research:
My research focus is to establish
the cellular, molecular, and genetic basis for the immunpathogenesis of
juvenile or type 1 diabetes and other autoimmune endocrine diseases.
We have concentrated our efforts on the role of antigens such as glutamate
decarboxylase (GAD) and the biology of antigen presenting cells as it relates
to the generation of protective and pathogenic immune responses in an animal
model of type 1 diabetes, the non obese diabetic mouse (NOD) as well as
in humans with an established high risk for this disease.
Our recent work has lead
to the identification of a number of immunophenotypes in NOD mice
and human subjects with a high risk for
Type 1 diabetes. These
immunophenotypes involve the regulation of prostaglandin metabolism in
macrophages/monocytes and dysregulation of pathways involved in activation
induced cell death in lymphocytes. Utilizing congenic mice we have identified
chromosomal intervals that contribute to these phenotypes. We are
currently evaluating candidate genes in these intervals
We are determining the role
of TNF- in the development of organ dysfunction, particularly liver injury
in a murine model of sepsis and inflammation. We have defined
that NOD mice are highly resistant to this form of liver injury in comparison
to other standard strains of mice. We are currently dissecting the genetic
contributions to this resistance using a congenic mouse approach.
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