Disease Programs

Diabetes

Marika Bogdani (PNRI, Medicine)

In spite of the clinical success, insulin-producing tissue has been offered to a limited number of diabetic patients. Limitations for both pancreas and islet transplantation include the relative lack of organ donors for allogeneic transplantation and the need for continuous immunosuppression. The successful islet transplants prepared by the different diabetes centers require islet preparations from more than one donor pancreata, thus large quantities of islets to be implanted in order to achieve insulin sufficiency even for limited time. An effective cell replacement strategy thus depends on the development of an abundant supply of beta cells and their protection from immune destruction. Different approaches will be explored to generate insulin-producing cells to expand the adult pancreatic beta cell with the aim to increase their mass and number prior to transplantation. New beta cells may be formed from the beta cell precursor cells and from beta cell themselves. Alternatively, cells with a common ontogeny with beta cells, and cells which might allow their manipulation or fate direction towards a beta cell phenotype will also be considered as a possible beta cell source.

Ake Lernmark, PhD (Medicine) (Adjunct Professor Immunology)

This group is internationally known for its work on the mechanisms underlying type 1 diabetes. The research is focused on genetic factors that contribute to islet autoimmunity, type 1 diabetes, or both. The spontaneously diabetic BB rat is used to dissect diabetes genes and a major contribution was the positional cloning of a major diabetes gene and the discovery of anew family of anti-apoptopic proteins. GAD65 autoantibodies the best predictive marker for type 1 diabetes was discovered by this investigator. The islet autoantibody assay are now widely used to classify diabetes and treatment studies to induce immunological tolerance have been initiated. The group leads one of the clinical centers for the NIH-supported TEDDY study aimed at identifying environmental factors that trigger the onset of islet autoimmunity.

Gerald Nepom, MD, PhD (UW Affiliate Professor, Immunology, and Director of BRI)

Dr. Nepom heads a laboratory program in translational immunology focused on tolerance mechanisms relevant to diabetes therapeutics. A number of approaches, including the use of genetics as predictive markers of disease susceptibility, and MHC tetramer analysis to stratify patients for clinical disease and response to therapy studies, are used in order to detect, modulate or block specific molecular pathways in type 1 diabetes disease pathogenesis. His interests also include mechanisms of initiating immune tolerance by use of embryonic, stem cell, or genetically modified cells and tissues.

Ian Sweet (Medicine)

The production of insulin-producing cells from stem cells is an area of intense investigation due to its potential for facilitating transplantation of this tissue into diabetics. A major issue in this area is to determine what characteristics define a beta cell such that one can prove that one has truly created a surrogate.

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