Susan Bonner-Weir investigates how the pancreatic beta cell changes with age and in response to challenges.

With a series of rodent models, Dr. Bonner-Weir has provided compelling evidence that adult pancreatic beta-cell mass increases in response to a metabolic need. Her lab has been examining the mechanisms of postnatal pancreatic growth, focusing on how the pancreatic beta cell changes with age and response to challenges.

The Bonner-Weir team provided the first strong evidence of multipotent facultative progenitor cells in the adult pancreatic ducts, first using transgenic mice over-expressing transforming growth factor-alpha, second in the partial pancreatectomy model, and third in cultured islet-depleted human pancreatic tissue. These were followed by lineage tracing experiments showing the ductal origin of the new islets formed after birth. More recently she has shown heterogeneity of duct cells suggesting that duct cells vary in their potential to serve as precursors for new endocrine and exocrine cells, thus helping us understand discrepant results found with other lineage tracing experiments. This new knowledge of endocrine pancreas growth after birth has important implications for understanding the mechanisms of response to injury and neoplasia of the pancreas as well as providing possible new insights into the pathogenesis of diabetes and new directions for therapy. As part of the Joslin 50-year Medalist study of individuals living more than 50 year with type 1 diabetes, she found insulin-positive beta cells in all 68 post-mortem pancreas examined. The pattern of insulin-positive beta cells as scattered as singlets or doublets or within some islets in a lobular pattern supports the concept that small numbers of new beta cells are constantly generated throughout life, but sadly in type 1 diabetes they are probably killed by autoimmunity as they mature.

Recent work has greatly expanded our understanding of heterogeneity among β cells in normal and pathological situations. The Bonner-Weir group showed that the neonatal immature β cells have a very different phenotype than adult β cells, and that the transcription factor MafA plays a key role in their functional maturation. They also made the important observation that thyroid hormone is important for β-cell maturation and this discovery is now widely used for directing embryonic stem cells to become β cells. Yet another major finding was the demonstration that β-cell aging (senescence) can be accelerated by metabolic stress (e.g., increased insulin resistance or hyperglycemia) and could thus play a key role in the development of diabetes. Thus, she and her group have shown heterogeneity of β cells at different life stages spanning from immaturity to senescence and that these stages have different phenotypes and function.

Biosketch

Dr. Susan Bonner-Weir is Senior Investigator, Joslin Diabetes Center and Professor of Medicine, Harvard Medical School. She holds the Diabetes Research and Wellness Chair. She graduated from Rice University and received her Ph.D. in biology from Case Western Reserve University. Dr. Bonner-Weir was elected as a Fellow of the American Association for the Advancement of Science (AAAS) in 2012. She will receive the Helmhotz Diabetes Award at the 9th Helmholtz Diabetes conference May 2021. For over 35 years she has focused on the endocrine pancreas (the islets of Langerhans) in three areas:

1) Islet architecture and its implications for function;
2) Regulation of β-cell mass and function in health and disease;
3) Changes in β-cell phenotype throughout life

She is currently exploring ways to develop a reliable source of new beta-cells.

Bonner-Weir has published over 210 peer-reviewed papers and numerous book chapters and reviews. She has served on research grant review panels for the NIH, American Diabetes Association, Juvenile Diabetes Research Foundation, the Danish National Research Council, the European Research Council, and the California Institute of Regenerative Medicine and on the editorial boards of Endocrinology, American Journal of Physiology, Diabetes, Diabetes Technology and Therapeutics, Cell Transplantation, and Journal of Biological Chemistry.