Joslin Investigator Details

Research Interests

The main goal of the Section on Islet Transplantation and cell Biology is to make islet transplantation available as a treatment for diabetes. The major challenges are to find a source of sufficient numbers of insulin producing cells to supply all of those in need and to find ways to protect these cells from destruction by the immune system. Work is underway to explore the potential of porcine islet cells, adult stem cells from human pancreases, and embryonic stem cells. To protect transplanted islets from immune destruction, islets are encapsulated in alginate microbeads.

The group also makes major contributions to diabetes investigators in other laboratories by supplying isolated islets for research and clinical programs. Human islets are provided for clinical islet transplantation and research, and islets from monkeys, pigs and rodents are supplied for a wide variety of preclinical projects.

Our more basic interests are concerned with the phenotype and function of pancreatic beta cells in the in vivo environment, whether in models of diabetes such as rats with partial pancreatectomy or glucose infusions, or with transplanted islets placed into a site such under the kidney capsule or in alginate beads transplanted into the peritoneal cavity. Recent work has focused upon assessment of transplanted human islets, the development of immature porcine islet tissue and various other precursor/stem cells when transplanted. The tools used for this work include analysis of gene expression, laser capture microdissection, genetic manipulation with viral vectors, immunostaining, quantitative morphometry, and measurement of insulin storage and secretion. This work is done in close collaboration with Drs. Susan Bonner-Weir and Arun Sharma.

Selected References:

Trivedi N, Hollister-Lock J, Lopez-Avalos MD, O'Neil JJ, Keegan M, Bonner- Weir S, Weir GC. Increase in beta-cell mass after transplantation of porcine neonatal pancreatic cell clusters is due to proliferation of beta- cells and differentiation of duct cells. Endocrinology, 2001, 142: 2115-2122.

Kaneto H, Xu G, Song K-H, Suzuma K, Sharma S, Bonner-Weir S, Weir GC. Activation of the Hexosamine Pathway Leads to Deterioration of Pancreatic Beta-Cell Function through the Induction of Oxidative Stress. J Biol Chem. 2001, 276: 31099-31104.

Duvivier-Kali VF, Omer A,. Parent RJ, O’Neil JJ, Weir GC. Complete protection of islets against allorejection and autoimmunity by a simple barium-alginate membrane. Diabetes. 2001, 50: 1698-1705.

Kaneto H, Suzuma K, Sharma A, Bonner-Weir S, King, GL and Weir GC Involvement of Protein Kinase C beta 2 in c-myc Induction by High Glucose in Pancreatic beta-Cells. J Biol Chem. 2002, 277:3680-3685.

Laybutt DR, Hasenkamp W, Kaneto H, Grey S Jonas J-C, Groff A, Trivedi N, Sharma A, Bonner-Weir S and Weir GC. Increased Expression of Antioxidant and Antiapoptotic Genes in Islets that may Contribute to Beta-Cell Survival During Chronic Hyperglycemia. Diabetes. 2002, 51: 413-423.

Omer A, Duvivier-Kali VF, Trivedi N, Wilmot K, Bonner-Weir S, Weir GC. Survival and maturation of microencapsulated porcine neonatal pancreatic cell clusters transplanted into immunocompetent diabetic mice. Diabetes 2003, 52:69-75.

Laybutt DR, Glandt M, Xu G, Ahn YB, Trivedi N, Bonner-Weir S, Weir GC. Critical Reduction in Beta-Cell Mass Results in Two Distinct Outcomes Over Time: Adaptation With Impaired Glucose Tolerance or Decompensated Diabetes. J Biol Chem. 2003, 278: 2997-3005

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 Transplantation 2004 , 4: 1991-2000

Omer A, Duvivier-Kali VF, Aschenbach W, Tchipashvili V, Laurie J. Goodyear LJ, Weir GC. Exercise induces hypoglycemia in rats with islet transplants. Diabetes 2004,53: 360-365

Weir GC, Bonner-Weir S. Five stages of evolving beta cell dysfunction during progression to diabetes. Diabetes 2004, 53, Suppl 3: :S16-21

King A, Lock J, Xu G, Bonner-Weir S, Weir GC. Islet transplantation outcomes are better with fresh islets and exendin-4 treatment. Diabetologia. 2005, 48: 2074-9.

Ahn YB, Xu G, Marselli L, Toschi E, Sharma A, Bonner-Weir S, Sgroi DC, Weir GC. Changes in gene expression in beta cells after islet isolation and transplantation using laser capture microdissection. Diabetologia 2006, in press.

Biographical Sketch:

Dr. Gordon Weir is Professor of Medicine at Harvard Medical School, Diabetes Research and Wellness Foundation Chair, and heads Joslin's Section on Islet Transplantation and Cell Biology. Dr. Weir completed his medical degree at Harvard Medical School and his residency training at University Hospital in Cleveland, OH. Training in endocrinology was obtained at Massachusetts General Hospital. Before coming to Joslin, Dr. Weir was Professor of Medicine at the Medical College of Virginia. When Dr. Weir first came to Joslin, he served as the Center's Medical Director for 9 years, in addition to conducting a broad research program. Dr. Weir is the recipient of numerous honors and serves and has served on the editorial boards of several prestigious journals, including the American Journal of Physiology, Journal of Clinical Endocrinology and Metabolism, and Transplantation. He recently served as Editor-in-Chief of the jour