|
|||||||
|
Dale Greiner, Ph.D.Academic Role: Professor
Faculty Appointment(s) In:
Other Affiliation(s):
Transplantation tolerance and autoimmune diabetes
Office: Suite 218
|
|
|||||
| INTRANET |
|
top print |
|
||||
| |||||||
Our major area of investigation is to understand the etiology and pathogenesis of autoimmune type I diabetes mellitus. Our approach focuses on two main areas, the understanding of the pathogenesis of type 1 diabetes so as to formulate means to prevent the disease, and the cure of those who are diabetic by induction of transplantation tolerance to islets of Langerhans. To investigate these two areas, we use two animal models of type 1 diabetes, the BB rat and the NOD mouse. In the BB rat, we have identified a regulatory T cell that prevents diabetes by the expression of a cell surface glycophosphatidylinositol-linked molecule called ART2. This molecule can mediate signal transduction events through src family tyrosine kinases, and also has NAD+ glycohydrolase activity. We are using genetic, molecular, and cellular approaches to determine whether one or both functions of the ART2 molecule are important in the immunoregulatory activity ART2++ T cells. In the NOD mouse, we are using genetic and cellular approaches to investigate the relationship of a strong resistance to transplantation tolerance with their expression of autoimmunity. In transplantation, we have developed a co-stimulation blockade-based protocol to induce permanent allograft tolerance to islets and skin in mice by treatment with donor-specific transfusion and anti-CD154 monoclonal antibody. This protocol also induces permanent survival of rat to mouse islet xenografts, and significantly prolongs skin xenograft survival. Our studies are now focused on understanding the mechanisms by which this co-stimulation blockade-based protocol induces tolerance to permit its translation to the clinic.
373 Plantation Street Worcester, MA 01605