Research
in my laboratory addresses the prevention and therapy of
type 1 diabetes. Prevention studies are focused on
discovering the causes and prevention of the body’s
autoimmune attack against the insulin-producing
pancreatic islet β-cells resulting in insulin-dependent
(type 1) diabetes. Therapeutic studies are focused on
identifying growth factors that can regenerate
pancreatic islet β-cells and cure type 1 diabetes. Our
studies are conducted in vivo in inbred animals (NOD
mice and BB rats) with autoimmune diabetes resembling
human type 1 diabetes, and in vitro with immune system
cells and pancreatic islet β-cells from NOD mice, BB
rats, and humans.
Our laboratory pioneered the concept that type 1 diabetes results from a disorder of immunoregulation in which a T helper 1 (Th1) subset of autoreactive T cells dominates over a Th2 regulatory (suppressor) subset, and that prevention of autoimmune destruction of islet β-cells might be achieved by deleting Th1 autoreactive cells and/or increasing Th2 regulatory cells. In support of this concept, we have found that immune adjuvants, such as CFA and BCG, prevent autoimmune diabetes in NOD mice and BB rats by inducing apoptosis and deletion of Th1-type cells.
In addition, we found that administration of interleukin-2 (IL-2), together with the immunosuppressive drug rapamycin (sirolimus), favored T cell apoptosis over proliferation and prevented autoimmune diabetes in NOD mice. IL-2 + rapamycin will be tested as a therapy to halt progressive autoimmune destruction of islet β-cells in humans with recently-diagnosed type 1 diabetes. In addition to the above type 1 diabetes prevention studies, our laboratory has recently identified growth factor peptides that induce islet β-cell neogenesis (regeneration) in adult human pancreatic islets in vitro, as well as in NOD mice with autoimmune diabetes. We are currently studying mechanisms of β-cell neogenesis using these growth factors. By combining strategies of arresting autoimmune destruction of pancreatic islet β-cells and regenerating β-cells, we hope to achieve our goal - to cure type 1 diabetes. Our research is supported by Juvenile Diabetes Foundation International, the Muttart Diabetes Research & Training Centre at the University of Alberta, The MacLachlan Fund of the University of Alberta Hospitals, and several biotechnology and pharmaceutical research contracts through the University of Alberta Research Services Office.