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Susan Bonner-Weir, Ph.D.

Dr. Bonner-Weir is a Senior Investigator in the Section on Islet Transplantation and Cell Biology at Joslin and Associate Professor of Medicine at Harvard Medical School. She received her doctoral degree in Biology from Case Western Reserve University and then completed postdoctoral training in islet morphology at Harvard Medical School and Joslin. She has served on the editorial boards of Diabetes, Endocrinology, American Journal of Physiology, Cell Transplantation and Journal of Biological Chemistry, and has been a member of the Juvenile Diabetes Research Foundation Scientific Review Committee, the American Diabetes Association Grant Review Panel and the Grant Review Panel for the California Institute of Regenerative Medicine.

Dr. Bonner-Weir’s laboratory has been studying the islets of Langerhans (the endocrine portion of the pancreas) and concentrating on three areas of research: (1) the architecture of the islets and implications for their function, (2) the regulation of the number of islet cells in the body, and (3) the factors involved in islet growth and differentiation. Now, Dr. Bonner-Weir’s main focus is the search for new sources of insulin-producing beta cells.

Research in her laboratory has already provided compelling evidence that the number of islet cells in the pancreas changes in response to the body’s increased or decreased demand for insulin. Using transgenic and knockout (genetically modified) mice as well as rat models, she also demonstrated that diabetes results from the failure of the pancreas to expand the number of islet cells to compensate for the body’s increased need for insulin—a condition that might result from greater insulin resistance (caused by obesity, for example), impaired function of the islet cells themselves (as in mature onset of diabetes in the young, or MODY) or a loss of insulin-producing cells (as in type 1 diabetes).
Dr. Bonner-Weir and her colleagues are working on generating new functional insulin-producing cells from adult pancreatic progenitor cells and embryonic stem cells. They have shown that the adult rat pancreas can regenerate in a process similar to embryonic pancreas development. Using lineage-tracing techniques they are identifying the cells that in vivo and in vitro give rise to new insulin-producing cells. In addition, her laboratory is identifying markers to assess the maturity of newly generated islet cells.

With respect to humans, Dr. Bonner-Weir’s laboratory has also shown that new islets can be formed in vitro from duct cells that have been isolated from the adult human pancreas. This finding offers hope that such duct cells might one day be used to provide islets for transplantation, possibly obviating the need for immunosuppressive drugs if the transplanted islets could be derived from the patient’s own cells.

These projects should make more tissue available for islet transplantation (beta-cell replacement therapy).

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

Bonner-Weir S, Toschi E, Inada A, Reitz P, Fonseca SY, Aye T, Sharma A. The pancreatic ductal epithelium serves as a potential pool of progenitor cells. Pediatr Diabetes 5:16-22, 2004.

Noguchi N, Kaneto H, Weir GC, Bonner-Weir S. PDX-1 protein containing its own Antennapedia-like protein transduction domain can transduce pancreatic duct and islet cells. Diabetes 52:1732-1737, 2003.

Bonner-Weir S, Sharma A. Pancreatic stem cells. J Pathol 197:518-526, 2002.

Bonner-Weir S. Postnatal pancreatic beta-cell growth. Endocrinology 141:1926-1929, 2000.

Bonner-Weir S, Taneja M, Weir GC, Tatarkiewicz K, Song K-H, Sharma A, O’Neil JJ. In vitro cultivation of human islets from expanded ductal tissue. Proc Natl Acad Sci U S A 97:7999-8004, 2000.

Xu G, Stoffers DA, Habener JF, Bonner-Weir S. Exendin-4 stimulates both beta-cell replication and neogenesis resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats. Diabetes 48:2270-2276, 1999.

Sharma A, Zangen DH, Reitz P, Taneja M, Lissauer ME, Miller CP, Weir GC, Habener JF, Bonner-Weir S. The homeodomain protein IDX-1 increases after an early burst of proliferation during pancreatic regeneration. Diabetes 48:507-513, 1999.

Finegood DT, Scaglia L, Bonner-Weir S. Dynamics of beta-cell mass in the growing rat pancreas: estimation with a simple mathematical model. Diabetes 44:249-256,1995.