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Gordon C. Weir, M.D.

Dr. Weir is Head of the Section on Islet Transplantation and Cell Biology and holds the Diabetes Research and Wellness Foundation Chair at Joslin. He is also a Professor of Medicine at Harvard Medical School and serves as the Director of the Clinical Islet Transplantation Programat Harvard, a cooperative effort among Joslin, Beth Israel Deaconess Medical Center, Massachusetts General Hospital and Brigham and Women’s Hospital. He is part of the Juvenile Diabetes Research Foundation Center on Immunological Tolerance in Type 1 Diabetes at Harvard Medical School. He also leads the Diabetes Working Group of the Harvard Stem Cell Institute. Dr. Weir received his medical degree from Harvard Medical School and has been at Joslin Diabetes Center since 1984.

One of the most important goals of diabetes research is to find sources of new beta cells (the islet cells in the pancreas that produce insulin) and to successfully transplant these cells into the pancreas. Dr. Weir has combined a career of caring for patients with diabetes with an intensive research focus on beta-cell replacement therapy.

His research interests include islet-cell transplantation and the function of islets in the normal and diabetic state. His laboratory focuses on four quests: (1) understanding the mechanisms that affect beta cells during diabetes; (2) making new beta cells for transplantation; (3) perfecting the procedures of beta-cell transplantation; and (4) protecting transplanted beta cells from destruction.

To find the mechanisms affecting beta cells in diabetes, Dr. Weir and his colleagues use gene expression and microarrays to determine the unique “machinery” of the normally functioning beta cell so they can understand what happens to beta cells stressed by the diabetic state.

A second area of interest—developing an alternative source of insulin-producing cells—is driven by the shortage of human donor pancreases. For this reason, Dr. Weir, Susan Bonner-Weir, Ph.D., and Arun Sharma, Ph.D., at Joslin are working with embryonic stem cells and adult precursor cells that have the capacity to become insulin-secreting cells. Dr. Weir collaborates with other scientists in the Harvard Stem Cell Institute. In addition, his group is investigating the use of genetic manipulation to convert liver cells into beta cells.
As part of the effort to improve islet-cell transplantation, Dr. Weir serves as Director of the Clinical Islet Transplantation Program at Harvard Medical School.  This team performed successful transplants on patients with type 1 diabetes, some of whom had a kidney transplant and others who did not.

A complementary project is an effort to protect transplanted islet cells from destruction by the immune system. Dr. Weir and colleagues at the Massachusetts Institute of Technology have developed methods that use encapsulation and gene therapy. With encapsulation, islet cells are enclosed in a capsule with a gel-like membrane that prevents immune cells from reaching and destroying the islet cells inside. Current efforts are focused on ways to improve the health and efficiency of insulin-producing cells contained within these capsules.

Selected References
Bonner-Weir S, Weir GC. New sources of pancreatic b-cells. Nat Biotechnol 23:857-861, 2005.

King A, Lock J, Xu G, Bonner-Weir S, Weir GC. Islet transplantation outcomes are better with fresh islets and exendin-4 treatment. Diabetologia 48:2074-2079, 2005.

Duvivier-Kali VF, Omer A, Lopez-Avalos MD, O’Neil JJ, Weir GC. Survival of microencapsulated adult pig islets in mice in spite of an antibody response. Am J Transplant 4:1991-2000, 2004.

Laybutt DR, Glandt M, Xu G, Ahn YB, Trivedi N, Bonner-Weir S, Weir GC critical reduction in b-cell mass results in two distinct outcomes over time adaptation with impaired glucose tolerance or decompensated diabetes. J Biol Chem 278:2997-3005, 2003.

Kaneto H, Xu G, Fujii N, Kim S, Bonner-Weir S, Weir GC. Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expression. J Biol Chem 277:30010-30018, 2002.