The Center also supports substantial clinical and basic science research programs to study this life-threatening, chronic disease and discover ways to prevent and cure childhood diabetes.
The Barbara Davis Center is in the forefront of investigation aimed at identifying the immune cells (lymphocytes) responsible for the pathogenesis of Type I diabetes and the molecular targets of these cells within the endocrine pancreas. Research at the center has found that a large proportion of T cells that attack the pancreatic islets recognize a portion of the insulin molecule itself as a target structure. These studies conducted through our Research Division represent a clear demonstration of a defined islet-specific target structure involved in the pathogenesis of Type I diabetes.
Another related arm of research at the Center focuses on islet cell transplantation as a treatment for existing Type I diabetes. Type I diabetes proves to be a formidable problem in the field of transplantation. In organ transplantation, such as with kidney or heart grafting, the transplant recipient must receive non-specific chemical immunosuppressive drugs to prevent immune rejection of the transplant. These immunosuppressive agents have a number of potentially serious side effects, but are justified because the transplant is necessary to sustain life. However, Type I diabetes is not immediately life-threatening, and so the use of conventional immunosuppressive agents is not justified except in extreme cases where the Type I diabetic recipient is already receiving a kidney transplant due to renal failure. One goal of research at the Center has therefore been to develop islet cell transplantation using minimal recipient immunosuppression. A series of studies demonstrate that it is possible to transplant foreign islet tissue into animals without immune suppression by pre-treating the donor islet tissue in order to reduce the ability of the tissue to elicit an immune reaction in the recipient.
A further major problem in islet transplantation is that the autoimmune damage that produces the original damage in Type I diabetes may also recur in an islet transplant. Preliminary studies performed by investigators at the Center have indicated that islets transplanted into human Type I diabetic recipients are also destroyed by an immune response and that the underlying autoimmunity in Type I diabetes may be an important obstacle in human islet transplantation.
As investigators get a better understanding of the immune cells that trigger islet destruction in this disease, our goal will be to apply this understanding toward preventing the development of diabetes in patients who are at risk for the disease, and controlling the immune system recognition of islet transplants. Programs of investigation are also being developed in the area of the genetic manipulation of endocrine precursor cells with the view to supplying abundant sources of functional beta cells for therapeutic purposes once the problems of immune rejection have been solved.