Joslin Investigator Details

A Harvard Medical School Affiliate

Welcome to the Joslin Research Website


	Joslin Investigator:

Susan Bonner-Weir, PhD

Investigator Specifics:

Professional Details:

CV not available

Member of Section:

Core Director:

Current Fellows, Students, or Lab Members:

Limor Yahalom, Ph. D.

Past Fellows, etc.:

Tandy Aye, MD

Tina Dalili-Shoaie, MD

Eelco de Koning, M.D., Ph.D.

Alexandra Haagensen, MD

Akari Inada, Ph.D.

Dohoon Kim, PhD, Ph.D.

Anne Marie Kloosterman, MB

Angela Koh, MD

Wan-Chun Li, PhD

Cindy Loomans, MD

Rina Morita, Ph.D.

Cameron Nienaber

Hirofumi Noguchi, MD

Petra Reitz

Ki Ho Song, MD

Stacey Su, MD

Gang Xu, MD

Shigeru Yatoh, M.D.

Sonya Yokoff Fonesca

Investigators

Adjunct Investigators

Fellows & Team Members

DERC Cores

Research Sections

Joslin Resources

Susan Bonner-Weir, PhD

Senior Investigator

Joslin Diabetes Center

Associate Professor

Harvard Medical School

9/11/1984 -

Research Interests

Senior Investigator Dr. Bonner-Weir and her colleagues believe that a better understanding of the regulation of pancreatic growth and differentiation may lead to new therapies, including generation of new beta cells and amplification of beta cells from the pancreas (either human or animal) to be used for transplantation. Her research has focused on the endocrine pancreas (the islets of Langerhans) in three areas: 1) the architecture of the islet and its implications for function; 2) the in vivo regulation of beta-cell mass; and 3) the factors involved in islet growth and differentiation.

With a series of rodent models they have provided compelling evidence that adult pancreatic beta-cell mass increases in response to a metabolic need and have been examining the mechanisms of this postnatal pancreatic growth. In the adult rat after partial pancreatectomy, massive regeneration occurs with both enhanced replication of preexisting beta cells and ductal expansion and subsequent differentiation into endocrine, exocrine or mature duct cells. They are defining the cells that are involved and the factors that are carefully orchestrated in vivo to stimulate the growth and differentiation of the beta cells. Another project is to define markers of newly formed beta cells. Additionally they have been successful in vitro cultivation of human islets from pancreatic ductal cells and are characterizing the cells that give rise to the new islets. Their overall hypothesis has been that in the adult pancreas duct cells act as pancreatic progenitors, such that with replication the mature duct cell regresses to a less differentiated cell (perhaps equivalent to a embryonic pancreatic duct cell) and regains its potential to differentiate into islet, acinar or mature duct cell, and that this phenotypic differentiation is directed by external signals or morphogens. Using the Cre-lox system for lineage tracing they have shown that mature duct cells serve as the progenitor for new islets and new acini after birth and after injury.

Selected References:

Finegood, D.T., Scaglia, L., Bonner-Weir, S., (Perspective) Dynamics of Beta Cell Mass in the growing rat pancreas: Estimation with a simple mathematical model. Diabetes, 1995, 44: 249-256.

Scaglia, L., Cahill, C.J., Finegood, D.T., Bonner-Weir, S., Apoptosis participates in the remodeling of the endocrine pancreas in the neonatal rat. Endocrinology, 1997, 138: 1736-1742.

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 1999; 48: 507-513.

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 1999; 48:2270-2276.

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 Nat Acad Science (USA) 2000; 97:7999-8004.

Bonner-Weir S, Life and death of the pancreatic beta cells. Trends in Endocrinology and Metabolism, 2000,11:375-378.

Bonner-Weir S. Beta cell turnover: its assessment and implications. Diabetes 2001, 50: Suppl 1:S20-24.

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 2003; 52: 1732-1737.

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. Pediatric Diabetes 2004, 5:16-22.

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

Bonner-Weir S, Weir GC. New sources of pancreatic beta cells. Nature Biotech. 2005; 23:857-861.

Dodge RR, Loomans C, Sharma A, Bonner-Weir S. Developmental pathways during in vitro progression of human islet neogenesis. Differentiation 2009, 77: 135-47

Inada A, Nienaber C, Katsuta H, Fujitani Y, Levine J, Morita R, Sharma A, Bonner-Weir S. CAII positive pancreatic cells are progenitors for both endocrine and exocrine pancreas after birth revision. PNAS 2008 105: 19915-19919.

Biographical Sketch:

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