My research involves the development of therapies for treating type 1 diabetes in a humanized version of the NOD mouse. Using NOD mice in which the mouse MHC class I has been replaced with a human variant linked to type 1 diabetes development, I am studying how several therapies can tolerize autoreactive CD8+ T cells selected on the human HLA. The first project revolves around using hematopoietic stem cell transplantation and induction of mixed chimerism to determine how protective MHC can tolerize autoreactive CD8+ T cells. A second project revolves around peptide-microsphere conjugates and how dosing pre-diabetic humanized-NOD mice with diabetogenic peptides can prevent diabetes development, and the mechanisms by which autoreactive CD8+ T cells are tolerized by these peptide-microsphere conjugates. A final side project/collaboration involves dissecting the mechanisms by which IFNϒ can act as an inhibitory cytokine for autoreactive CD8+ T cell expansion.
