Susan Bonner-Weir

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint Beta-cell precursors--a work in progress
    Gordon C Weir
    Nat Biotechnol 22:1095-6. 2004
  2. doi request reprint Transdifferentiation of pancreatic ductal cells to endocrine beta-cells
    Susan Bonner-Weir
    Joslin Diabetes Center and Harvard Medical School, 1 Joslin Place, Boston, MA 02215 USA
    Biochem Soc Trans 36:353-6. 2008
  3. ncbi request reprint How can we get more beta cells?
    Akari Inada
    Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
    Curr Diab Rep 6:96-101. 2006
  4. ncbi request reprint GLP-1/exendin-4 facilitates beta-cell neogenesis in rat and human pancreatic ducts
    Gang Xu
    Diabetes Res Clin Pract 73:107-10. 2006
  5. ncbi request reprint In vivo imaging of islet transplantation
    Natalia V Evgenov
    Molecular Imaging Laboratory, MGH MIT HMS Athinoula A Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital Harvard Medical School, Room 2301, Building 149, 13th Street, Charlestown, Massachusetts 02129, USA
    Nat Med 12:144-8. 2006
  6. pmc Stem cell approaches for diabetes: towards beta cell replacement
    Gordon C Weir
    Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA, and the Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA
    Genome Med 3:61. 2011
  7. pmc Islet neogenesis: a possible pathway for beta-cell replenishment
    Susan Bonner-Weir
    Joslin Diabetes Center, Department of Medicine, Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA
    Rev Diabet Stud 9:407-16. 2012
  8. ncbi request reprint Stem cells in diabetes: what has been achieved
    Susan Bonner-Weir
    Department of Medicine, Harvard Medical School, and Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, Mass 02215, USA
    Horm Res 60:10. 2003
  9. ncbi request reprint Assessment of human islet preparations to be used for islet expansion, survival, or transplant
    Susan Bonner-Weir
    Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Diabetes Technol Ther 6:493-4. 2004
  10. ncbi request reprint The pancreatic ductal epithelium serves as a potential pool of progenitor cells
    Susan Bonner-Weir
    Department of Medicine, Research Division, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA
    Pediatr Diabetes 5:16-22. 2004

Research Grants

  1. Phenotypic Analysis of Young and Old Beta Cells
    Susan Bonner Weir; Fiscal Year: 2007
  2. Strategies to Identify In Vitro Islet Progenitors
    Susan Bonner Weir; Fiscal Year: 2007
  3. Phenotypic Analysis of Young and Old Beta Cells
    Susan Bonner Weir; Fiscal Year: 2006
  4. Strategies to Identify In Vitro Islet Progenitors
    Susan Bonner Weir; Fiscal Year: 2006
  5. Phenotypic Analysis of Young and Old Beta Cells
    Susan Bonner Weir; Fiscal Year: 2005
  6. MECHANISMS OF ISLET GROWTH AND DIFFERENTIATION
    Susan Bonner Weir; Fiscal Year: 1993
  7. MECHANISMS OF ISLET GROWTH AND DIFFERENTIATION
    Susan Bonner Weir; Fiscal Year: 1992

Detail Information

Publications87

  1. ncbi request reprint Beta-cell precursors--a work in progress
    Gordon C Weir
    Nat Biotechnol 22:1095-6. 2004
  2. doi request reprint Transdifferentiation of pancreatic ductal cells to endocrine beta-cells
    Susan Bonner-Weir
    Joslin Diabetes Center and Harvard Medical School, 1 Joslin Place, Boston, MA 02215 USA
    Biochem Soc Trans 36:353-6. 2008
    ....
  3. ncbi request reprint How can we get more beta cells?
    Akari Inada
    Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
    Curr Diab Rep 6:96-101. 2006
    ..Major questions still remain: whether there are true pancreatic stem cells, what are the pancreatic progenitor cells after birth, and whether expanded beta cells themselves could serve as the source...
  4. ncbi request reprint GLP-1/exendin-4 facilitates beta-cell neogenesis in rat and human pancreatic ducts
    Gang Xu
    Diabetes Res Clin Pract 73:107-10. 2006
  5. ncbi request reprint In vivo imaging of islet transplantation
    Natalia V Evgenov
    Molecular Imaging Laboratory, MGH MIT HMS Athinoula A Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital Harvard Medical School, Room 2301, Building 149, 13th Street, Charlestown, Massachusetts 02129, USA
    Nat Med 12:144-8. 2006
    ..We anticipate that the information obtained in this study would ultimately result in the ability to detect and monitor islet engraftment in humans, which would greatly aid the clinical management of this disease...
  6. pmc Stem cell approaches for diabetes: towards beta cell replacement
    Gordon C Weir
    Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA, and the Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA
    Genome Med 3:61. 2011
    ..Herein, we review recent advances in our understanding of diabetes and beta cell biology at the genomic level, and we discuss how stem-cell-based approaches might be used for replacing beta cells and for treating diabetes...
  7. pmc Islet neogenesis: a possible pathway for beta-cell replenishment
    Susan Bonner-Weir
    Joslin Diabetes Center, Department of Medicine, Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA
    Rev Diabet Stud 9:407-16. 2012
    ..Herein, we discuss the role of neogenesis in normal growth and regeneration, as learned from rodent models, followed by an analysis of what has been found in humans. ..
  8. ncbi request reprint Stem cells in diabetes: what has been achieved
    Susan Bonner-Weir
    Department of Medicine, Harvard Medical School, and Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, Mass 02215, USA
    Horm Res 60:10. 2003
    ..Each new report has been met with a mixture of excitement and skepticism. With continued efforts and rigorous assessments, hopefully the potential of generating enough new beta-cells from stem cells will be realized...
  9. ncbi request reprint Assessment of human islet preparations to be used for islet expansion, survival, or transplant
    Susan Bonner-Weir
    Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Diabetes Technol Ther 6:493-4. 2004
  10. ncbi request reprint The pancreatic ductal epithelium serves as a potential pool of progenitor cells
    Susan Bonner-Weir
    Department of Medicine, Research Division, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA
    Pediatr Diabetes 5:16-22. 2004
    ..We will develop our case for this hypothesis in this perspective...
  11. ncbi request reprint New sources of pancreatic beta-cells
    Susan Bonner-Weir
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, Massachusetts 02215, USA
    Nat Biotechnol 23:857-61. 2005
    ..Recent progress in the search for new sources of beta-cells has opened promising new opportunities and spawned clinical trials...
  12. ncbi request reprint Are there pancreatic progenitor cells from which new islets form after birth?
    Susan Bonner-Weir
    Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215, USA
    Nat Clin Pract Endocrinol Metab 2:240-1. 2006
  13. ncbi request reprint Pancreatic stem cells
    Susan Bonner-Weir
    Section of Islet Transplantation and Cellular Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
    J Pathol 197:519-26. 2002
    ..However, no clearly identifiable adult pancreatic stem cell has been found as yet. The putative pancreatic stem cells will be the focus of this review...
  14. pmc In vitro cultivation of human islets from expanded ductal tissue
    S Bonner-Weir
    Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 97:7999-8004. 2000
    ..This approach may provide a potential new source of pancreatic islet cells for transplantation...
  15. ncbi request reprint Life and death of the pancreatic beta cells
    S Bonner-Weir
    Joslin Diabetes Center, Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA
    Trends Endocrinol Metab 11:375-8. 2000
    ..The emphasis in this review is on recent insights on the natural history of the beta cell in a normal pancreas: sources of renewal, survival and changes in differentiation...
  16. ncbi request reprint beta-cell turnover: its assessment and implications
    S Bonner-Weir
    Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Diabetes 50:S20-4. 2001
    ..Two major implications of beta-cell turnover are that 1) at any time, the beta-cells would be at different ages and 2) any limitation on replacement could have dire consequences for glucose homeostasis...
  17. pmc A switch from MafB to MafA expression accompanies differentiation to pancreatic beta-cells
    Wataru Nishimura
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, MA 02215, USA
    Dev Biol 293:526-39. 2006
    ..Thus, this redundancy in the function and expression of the large-Maf factors may explain the normal islet morphology observed in the MafA knockout mice at birth...
  18. ncbi request reprint Involvement of protein kinase C beta 2 in c-myc induction by high glucose in pancreatic beta-cells
    Hideaki Kaneto
    Section on Islet Transplantation and Cell Biology and Section on Vascular Cell Biology, Joslin Diabetes Center, Boston, Massachusetts 02215, USA
    J Biol Chem 277:3680-5. 2002
    ..These results suggest that at least some of the reduction of insulin gene transcription found in the diabetic state is mediated by PKC beta2 regulation of c-myc expression...
  19. ncbi request reprint NeuroD and reaggregation induce beta-cell specific gene expression in cultured hepatocytes
    Shigeru Yatoh
    Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
    Diabetes Metab Res Rev 23:239-49. 2007
    ..Our goal was to convert adult mouse hepatocytes to pancreatic beta-cells...
  20. ncbi request reprint Overexpression of c-Myc in beta-cells of transgenic mice causes proliferation and apoptosis, downregulation of insulin gene expression, and diabetes
    D Ross Laybutt
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, Massachusetts, USA
    Diabetes 51:1793-804. 2002
    ....
  21. ncbi request reprint Induction of c-Myc expression suppresses insulin gene transcription by inhibiting NeuroD/BETA2-mediated transcriptional activation
    Hideaki Kaneto
    Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
    J Biol Chem 277:12998-3006. 2002
    ..This mechanism may explain some of the beta-cell dysfunction found in diabetes...
  22. pmc PDX1 in ducts is not required for postnatal formation of β-cells but is necessary for their subsequent maturation
    Lili Guo
    Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts
    Diabetes 62:3459-68. 2013
    ..Even at 10 weeks, islets expressed immaturity markers. Thus, we conclude that Pdx1 is not necessary for the postnatal formation of β-cells but is essential for their full maturation to glucose-responsive β-cells. ..
  23. ncbi request reprint Downregulation of GLP-1 and GIP receptor expression by hyperglycemia: possible contribution to impaired incretin effects in diabetes
    Gang Xu
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
    Diabetes 56:1551-8. 2007
    ..Taken together, GLP-1 and GIP receptor expression is decreased with chronic hyperglycemia, and this decrease likely contributes to the impaired incretin effects found in diabetes...
  24. ncbi request reprint Transplantation of islets transduced with CTLA4-Ig and TGFbeta using adenovirus and lentivirus vectors
    Justin R Fernandes
    Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Room 535, Boston, MA 02215, USA
    Transpl Immunol 13:191-200. 2004
    ..The purpose of this study was to see if lentiviral (LV) vectors would provide superior results compared with adenoviral vectors...
  25. pmc Modification of adverse inflammation is required to cure new-onset type 1 diabetic hosts
    Maria Koulmanda
    Department of Surgery, Harvard Medical School, and Islet Transplantation Research Laboratory, Massachusetts General Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:13074-9. 2007
    ..Thus, this triple-therapy regimen, possessing both tolerance-inducing and select antiinflammatory properties, may represent a prototype for therapies able to restore euglycemia and self-tolerance in T1DM...
  26. ncbi request reprint Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expression
    Hideaki Kaneto
    Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, Massachusetts 02215, USA
    J Biol Chem 277:30010-8. 2002
    ..In conclusion, activation of JNK is involved in the reduction of insulin gene expression by oxidative stress, and suppression of the JNK pathway protects beta-cells from oxidative stress...
  27. pmc Thyroid hormone promotes postnatal rat pancreatic β-cell development and glucose-responsive insulin secretion through MAFA
    Cristina Aguayo-Mazzucato
    Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
    Diabetes 62:1569-80. 2013
    ..Thus, TH can be considered a physiological regulator of functional maturation of β cells via its induction of Mafa...
  28. doi request reprint Lack of evidence for recipient precursor cells replenishing β-cells in transplanted islets
    Yoshiyuki Hamamoto
    Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
    Cell Transplant 19:1563-72. 2010
    ..This study provides further support for the concept that recipient precursor cells do not produce new β-cells in grafts of transplanted islets...
  29. pmc Activation of pancreatic-duct-derived progenitor cells during pancreas regeneration in adult rats
    Wan Chun Li
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
    J Cell Sci 123:2792-802. 2010
    ..This mechanism of regeneration relies mainly on the plasticity of the differentiated cells within the pancreas...
  30. pmc Gene expression profiles of Beta-cell enriched tissue obtained by laser capture microdissection from subjects with type 2 diabetes
    Lorella Marselli
    Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center and the Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
    PLoS ONE 5:e11499. 2010
    ..Changes in gene expression in pancreatic beta-cells from type 2 diabetes (T2D) should provide insights into their abnormal insulin secretion and turnover...
  31. pmc Differentiation of pancreatic endocrine progenitors reversibly blocked by premature induction of MafA
    Kaihui Hu He
    Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, United States
    Dev Biol 385:2-12. 2014
    ....
  32. pmc Concise review: pancreas regeneration: recent advances and perspectives
    Philippe A Lysy
    Joslin Diabetes Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts, USA
    Stem Cells Transl Med 1:150-9. 2012
    ..Herein, we discuss recent advances in the search for β-cell replacement therapies, current strategies for circumventing the immune system, and mandatory steps for new techniques to be translated from bench to clinics...
  33. pmc Gene expression of purified beta-cell tissue obtained from human pancreas with laser capture microdissection
    Lorella Marselli
    Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02215, USA
    J Clin Endocrinol Metab 93:1046-53. 2008
    ..Assessment is complicated when isolated islets are studied because of contamination by non-beta-cells and the trauma of the isolation procedure...
  34. doi request reprint Adult mouse intrahepatic biliary epithelial cells induced in vitro to become insulin-producing cells
    Masaki Nagaya
    Research Division, Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02215, USA
    J Endocrinol 201:37-47. 2009
    ..This approach may lead to a new source of beta-cells that can be used for transplantation in diabetes...
  35. ncbi request reprint Evidence for a role of the ubiquitin-proteasome pathway in pancreatic islets
    Maria D Lopez-Avalos
    Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
    Diabetes 55:1223-31. 2006
    ....
  36. pmc Carbonic anhydrase II-positive pancreatic cells are progenitors for both endocrine and exocrine pancreas after birth
    Akari Inada
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 105:19915-9. 2008
    ..This identification of a differentiated pancreatic cell type as an in vivo progenitor of all differentiated pancreatic cell types has implications for a potential expandable source for new islets for replenishment therapy for diabetes...
  37. ncbi request reprint Differentiation of affinity-purified human pancreatic duct cells to beta-cells
    Shigeru Yatoh
    Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
    Diabetes 56:1802-9. 2007
    ..Thus, purified duct cells from adult human pancreas can differentiate to insulin-producing cells...
  38. ncbi request reprint Survival and maturation of microencapsulated porcine neonatal pancreatic cell clusters transplanted into immunocompetent diabetic mice
    Abdulkadir Omer
    Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Diabetes 52:69-75. 2003
    ..In conclusion, NPCCs encapsulated with simple barium alginate can differentiate into beta-cells and reverse high blood glucose levels in immunocompetent mice without immunosuppression for >20 weeks...
  39. pmc Preferential reduction of beta cells derived from Pax6-MafB pathway in MafB deficient mice
    Wataru Nishimura
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, USA
    Dev Biol 314:443-56. 2008
    ..Thus, Pax6 acts upstream of MafB, which in turn may trigger the expression of insulin and regulate the PDX-1 and MafA expression required for beta-cell maturation...
  40. ncbi request reprint Normal relationship of beta- and non-beta-cells not needed for successful islet transplantation
    Aileen J F King
    Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215, USA
    Diabetes 56:2312-8. 2007
    ..It is therefore likely that islet non-beta-cells are not essential for successful islet transplantation...
  41. ncbi request reprint Macrophage depletion improves survival of porcine neonatal pancreatic cell clusters contained in alginate macrocapsules transplanted into rats
    Abdulkadir Omer
    Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
    Xenotransplantation 10:240-51. 2003
    ..In this study, the effect of peritoneal macrophage depletion on the biocompatibility of alginate macrocapsules and function of macroencapsulated porcine neonatal pancreatic cell clusters (NPCCs) was investigated...
  42. pmc Developmental pathways during in vitro progression of human islet neogenesis
    Rikke Dodge
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA
    Differentiation 77:135-47. 2009
    ..We suggest that appropriate manipulation of these differentiation-associated pathways will enhance the efficiency of differentiation of insulin-producing beta-cells in this in vitro model...
  43. ncbi request reprint Protein-tyrosine phosphatase 1B deficiency reduces insulin resistance and the diabetic phenotype in mice with polygenic insulin resistance
    Bingzhong Xue
    Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    J Biol Chem 282:23829-40. 2007
    ..Thus, even in the setting of high genetic risk for diabetes, reducing PTP1B is partially protective, further demonstrating its attractiveness as a target for prevention and treatment of type 2 diabetes...
  44. pmc p38 MAPK is a major regulator of MafA protein stability under oxidative stress
    Takuma Kondo
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Mol Endocrinol 23:1281-90. 2009
    ..Therefore, preventing p38 MAPK-mediated degradation of MafA represents a novel approach to improve beta-cell function...
  45. pmc Regenerating pancreatic beta-cells: plasticity of adult pancreatic cells and the feasibility of in-vivo neogenesis
    Kirstine Juhl
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, Massachusetts 02215, USA
    Curr Opin Organ Transplant 15:79-85. 2010
    ..This review will summarize recent advances in in-vivo generation of beta-cells from cells that are not beta-cells (neogenesis) and discuss ways to overcome the limitations of this process...
  46. ncbi request reprint Development and retroviral transduction of porcine neonatal pancreatic islet cells in monolayer culture
    Krystyna Tatarkiewicz
    Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
    Dev Growth Differ 45:39-50. 2003
    ..Furthermore, in such a culture setting, precursor duct cells have a high rate of proliferation and are more efficiently transduced with a retrovirus-based reporter gene than are beta cells...
  47. pmc Protective unfolded protein response in human pancreatic beta cells transplanted into mice
    Jeffrey Kennedy
    Section on Islet Cell Biology and Regenerative Medicine, Research Division, Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 5:e11211. 2010
    ..There is great interest about the possible contribution of ER stress to the apoptosis of pancreatic beta cells in the diabetic state and with islet transplantation...
  48. ncbi request reprint Critical reduction in beta-cell mass results in two distinct outcomes over time. Adaptation with impaired glucose tolerance or decompensated diabetes
    D Ross Laybutt
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, Massachusetts 02215, USA
    J Biol Chem 278:2997-3005. 2003
    ..Thus, both the severity and duration of hyperglycemia appear to contribute to the deterioration of the beta-cell phenotype found in diabetes...
  49. pmc Sustained NF-κB activation and inhibition in β-cells have minimal effects on function and islet transplant outcomes
    Aileen J F King
    Diabetes Research Group, King s College London, London, United Kingdom Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 8:e77452. 2013
    ....
  50. pmc Pancreatic duct ligation after almost complete β-cell loss: exocrine regeneration but no evidence of β-cell regeneration
    Claudia Cavelti-Weder
    Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, One Joslin Place, Boston, Massachusetts 02215
    Endocrinology 154:4493-502. 2013
    ..We conclude that β-cells and acinar cells, although originating from the same precursors during development, have very distinct regenerative potentials in our PDL model in adult rats. ..
  51. ncbi request reprint Induced ICER Igamma down-regulates cyclin A expression and cell proliferation in insulin-producing beta cells
    Akari Inada
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
    Biochem Biophys Res Commun 329:925-9. 2005
    ..Since ICER Igamma is greatly increased in diabetes as well as in FFA- or high glucose-treated islets, this effect may in part exacerbate diabetes by limiting beta-cell proliferation...
  52. doi request reprint Bone marrow or foetal liver cells fail to induce islet regeneration in diabetic Akita mice
    Tomoyuki Akashi
    Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
    Diabetes Metab Res Rev 24:585-90. 2008
    ..In this study, we carried out bone marrow and foetal liver cell transplantation to determine if these cells could differentiate into pancreatic beta-cells or promote regeneration...
  53. ncbi request reprint Increased expression of antioxidant and antiapoptotic genes in islets that may contribute to beta-cell survival during chronic hyperglycemia
    D Ross Laybutt
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, Massachusetts, USA
    Diabetes 51:413-23. 2002
    ..In conclusion, beta-cell adaptation to chronic hyperglycemia and, hence, increased insulin demand is accompanied by the induction of protective stress genes that may contribute to the survival of hypertrophied beta-cells...
  54. ncbi request reprint Suppression of beta cell energy metabolism and insulin release by PGC-1alpha
    J Cliff Yoon
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02215, USA
    Dev Cell 5:73-83. 2003
    ..These results strongly suggest that PGC-1alpha plays a key functional role in the beta cell and is involved in the pathogenesis of the diabetic phenotype...
  55. pmc Subpopulations of GFP-marked mouse pancreatic β-cells differ in size, granularity, and insulin secretion
    Hitoshi Katsuta
    Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Endocrinology 153:5180-7. 2012
    ..The three populations from the youngest had larger cells (forward scatter) and less granularity (side scatter) than those from the adults. This approach opens up new ways to advance knowledge about β-cell heterogeneity...
  56. ncbi request reprint PDX-1 protein containing its own antennapedia-like protein transduction domain can transduce pancreatic duct and islet cells
    Hirofumi Noguchi
    Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Diabetes 52:1732-7. 2003
    ....
  57. ncbi request reprint Five stages of evolving beta-cell dysfunction during progression to diabetes
    Gordon C Weir
    Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
    Diabetes 53:S16-21. 2004
    ..For type 1 diabetes, as remission develops, progression from stage 4 to stage 2 is typically found. Delineation of these stages provides insight into the pathophysiology of both progression and remission of diabetes...
  58. pmc Expression of MafA in pancreatic progenitors is detrimental for pancreatic development
    Wataru Nishimura
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Dev Biol 333:108-20. 2009
    ..These findings imply that MafA should be used to enhance maturation, rather than specification, of beta-cells from stem/progenitor cells...
  59. pmc Curative and beta cell regenerative effects of alpha1-antitrypsin treatment in autoimmune diabetic NOD mice
    Maria Koulmanda
    Departments of Surgery and Medicine, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:16242-7. 2008
    ..Indeed, the functional mass of beta cells expands in AAT-treated diabetic NOD mice...
  60. doi request reprint Laser capture microdissection of human pancreatic beta-cells and RNA preparation for gene expression profiling
    Lorella Marselli
    Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
    Methods Mol Biol 560:87-98. 2009
    ..We have developed a protocol of rapid tissue dehydration followed by identification of human beta-cells by their intrinsic autofluorescence, which allows laser microdissection for gene-profiling studies...
  61. ncbi request reprint Timing and expression pattern of carbonic anhydrase II in pancreas
    Akari Inada
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Dev Dyn 235:1571-7. 2006
    ..Thus, we believe that the CAII gene could serve as a useful pancreatic duct cell marker...
  62. pmc Identification of markers for newly formed beta-cells in the perinatal period: a time of recognized beta-cell immaturity
    Tandy Aye
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, Massachusetts 02215, USA
    J Histochem Cytochem 58:369-76. 2010
    ....
  63. ncbi request reprint Importance of hyperglycemia on the primary function of allogeneic islet transplants
    Leila Makhlouf
    Laboratory of Immunogenetics and Transplantation, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02215, USA
    Transplantation 76:657-64. 2003
    ..In this study, we investigated the influence of hyperglycemia on primary function of allogeneic islets transplanted into spontaneously diabetic recipients (NOD) or streptozotocin-induced diabetic mice (BALB/c)...
  64. pmc Residual insulin production and pancreatic ß-cell turnover after 50 years of diabetes: Joslin Medalist Study
    Hillary A Keenan
    Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA
    Diabetes 59:2846-53. 2010
    ..To evaluate the extent of pancreatic β-cell function in a large number of insulin-dependent diabetic patients with a disease duration of 50 years or longer (Medalists)...
  65. ncbi request reprint Mechanism of PDX-1 protein transduction
    Hirofumi Noguchi
    Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA
    Biochem Biophys Res Commun 332:68-74. 2005
    ....
  66. pmc Islet β cell mass in diabetes and how it relates to function, birth, and death
    Gordon C Weir
    Section on Islet Cell Biology and Regenerative Medicine, Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Ann N Y Acad Sci 1281:92-105. 2013
    ..Learning more about the relationships between β cell mass, turnover, and function and finding ways to restore β cell mass are among the most urgent priorities for diabetes research...
  67. ncbi request reprint Genetic regulation of metabolic pathways in beta-cells disrupted by hyperglycemia
    D Ross Laybutt
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, Massachusetts 02215, USA
    J Biol Chem 277:10912-21. 2002
    ..This global maladaptation in gene expression at the time of increased secretory demand may contribute to the beta-cell dysfunction found in diabetes...
  68. pmc A dominant role for glucose in beta cell compensation of insulin resistance
    Gordon C Weir
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Clin Invest 117:81-3. 2007
    ..The study also provides strong evidence that insulin receptor substrate 2 (Irs2), which is known to have major effects on beta cell growth and survival, is a key downstream mediator of the effects of glucose found in this study...
  69. ncbi request reprint p16INK4a induces an age-dependent decline in islet regenerative potential
    Janakiraman Krishnamurthy
    Department of Medicine, The Lineberger Comprehensive Cancer Center, The University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    Nature 443:453-7. 2006
    ..These genetic data support the view that an age-induced increase of p16INK4a expression limits the regenerative capacity of beta-cells with ageing...
  70. doi request reprint Stem cell therapy for type 1 diabetes mellitus
    Cristina Aguayo-Mazzucato
    Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA
    Nat Rev Endocrinol 6:139-48. 2010
    ....
  71. pmc Loss of Ncb5or results in impaired fatty acid desaturation, lipoatrophy, and diabetes
    Kevin Larade
    Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 283:29285-91. 2008
    ....
  72. pmc Finally! A human pancreatic β cell line
    Gordon C Weir
    Section on Islet Cell Biology and Regenerative Medicine, Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Clin Invest 121:3395-7. 2011
    ....
  73. ncbi request reprint In vivo multimodal imaging of transplanted pancreatic islets
    Zdravka Medarova
    MGH MIT HMS Athinoula A Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA
    Nat Protoc 1:429-35. 2006
    ..This information would be essential not only for the long-term monitoring of graft function but also for the design of improved transplantation and immunomodulatory methods...
  74. pmc Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction
    Maciej Borowiec
    Research Division, Department of Medicine, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 106:14460-5. 2009
    ..1. These actions are greatly attenuated by the Ala71Thr mutation. These findings point to BLK as a previously unrecognized modulator of beta-cell function, the deficit of which may lead to the development of diabetes...
  75. ncbi request reprint Induction of pancreatic stem/progenitor cells into insulin-producing cells by adenoviral-mediated gene transfer technology
    Hirofumi Noguchi
    Diabetes Research Institute Japan, Toyoake, Aichi 470 1192, Japan
    Cell Transplant 15:929-38. 2006
    ..These data suggest that the overexpression of transcription factors, especially NeuroD, facilitates pancreatic stem/progenitor cell differentiation into insulin-producing cells...
  76. ncbi request reprint Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes
    Alexandra E Butler
    Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    Diabetes 52:102-10. 2003
    ....
  77. ncbi request reprint Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea
    Kun Ho Yoon
    Department of Endocrinology and Metabolism, Immunology, and Cell Biology Core Laboratory, Institutes of Medical Science, The Catholic University of Korea, Seoul, Korea 137 701
    J Clin Endocrinol Metab 88:2300-8. 2003
    ..Moreover, decreased beta-cell but increased alpha-cell proportion in the islets suggests for a selective beta-cell loss in the pathogenesis of Korean type 2 diabetes...
  78. pmc Overexpression of inducible cyclic AMP early repressor inhibits transactivation of genes and cell proliferation in pancreatic beta cells
    Akari Inada
    Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606 8507, Japan
    Mol Cell Biol 24:2831-41. 2004
    ..These results suggest that CRE and CRE-binding factors have an important role in pancreatic beta-cell physiology not only directly by regulation of gene trans-activation but also indirectly by regulation of beta-cell mass...
  79. ncbi request reprint Imaging beta-cell death with a near-infrared probe
    Zdravka Medarova
    MGH MIT HMS Athinoula A Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital Harvard Medical School, Charlestown, MA 02129, USA
    Diabetes 54:1780-8. 2005
    ....
  80. ncbi request reprint In vivo imaging of immune rejection in transplanted pancreatic islets
    Natalia V Evgenov
    Molecular Imaging Laboratory, Department of Radiology, Massachusetts General Hospital Massachusetts Institute of Technology Harvard Medical School, Charlestown, MA 02129, USA
    Diabetes 55:2419-28. 2006
    ..We believe that this agent, in combination with our preclinical model of islet transplantation, will facilitate the transition of imaging immune rejection to clinical trials...
  81. doi request reprint Preservation of beta-cell function by targeting beta-cell mass
    Eelco J P de Koning
    Department of Nephrology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
    Trends Pharmacol Sci 29:218-27. 2008
    ..In this review, we address the mechanisms involved in beta-cell dysfunction and beta-cell loss, and provide a rationale for pharmacological intervention for the preservation and/or expansion of beta-cell mass in type 2 diabetes...
  82. ncbi request reprint Photo-acceleration of protein release from endosome in the protein transduction system
    Masayuki Matsushita
    Department of Physiology, Okayama University Graduate School of Medicine and Dentistry, 2 5 1 Shikata cho, Okayama 700 8558, Japan
    FEBS Lett 572:221-6. 2004
    ..Moreover, FITC-11R-p53 protein was released from endosomes following stimulation with light. These data suggest that photo-acceleration is a more efficient strategy in terms of the protein transduction system...
  83. ncbi request reprint Toward development of imaging modalities for islets after transplantation: insights from the National Institutes of Health Workshop on Beta Cell Imaging
    Breay W Paty
    Department of Medicine, University of Alberta, Edmonton, Canada
    Transplantation 77:1133-7. 2004
    ..To better understand the fate of transplanted islets and the relationship between transplanted islet mass, graft function, and overall glucose homeostasis, an accurate and reproducible method of imaging islets in vivo is needed...
  84. pmc Establishment of a diabetic mouse model with progressive diabetic nephropathy
    Akari Inada
    Department of Diabetes and Clinical Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan
    Am J Pathol 167:327-36. 2005
    ..Thus, similar to human diabetic nephropathy, ICER Igamma transgenic mice exhibit a stable and progressive phenotype of diabetic kidney disease due solely to chronic hyperglycemia without other modulating factors...
  85. pmc Metabolic decompensation in pump users due to lispro insulin precipitation
    Howard A Wolpert
    Joslin Diabetes Center, Boston, MA 02215, USA
    BMJ 324:1253. 2002
  86. ncbi request reprint BETA2/NeuroD protein can be transduced into cells due to an arginine- and lysine-rich sequence
    Hirofumi Noguchi
    Dept of Transplantation and Immunology, Kyoto University Graduate School of Medicine, Sakyo ku, Kyoto 606 8507, Japan
    Diabetes 54:2859-66. 2005
    ..These data suggest that BETA2/NeuroD protein transduction could be a safe and valuable strategy for enhancing insulin gene transcription without requiring gene transfer technology...

Research Grants18

  1. Phenotypic Analysis of Young and Old Beta Cells
    Susan Bonner Weir; Fiscal Year: 2007
    ..Another important outcome of this research should be valuable information about such practical questions as what will lead to successful long-term islet transplantation. ..
  2. Strategies to Identify In Vitro Islet Progenitors
    Susan Bonner Weir; Fiscal Year: 2007
    ..Identifying such cell(s) would then direct focus on the expansion and differentiation of that cell type to a sustainable source of new beta cells. ..
  3. Phenotypic Analysis of Young and Old Beta Cells
    Susan Bonner Weir; Fiscal Year: 2006
    ..Another important outcome of this research should be valuable information about such practical questions as what will lead to successful long-term islet transplantation. ..
  4. Strategies to Identify In Vitro Islet Progenitors
    Susan Bonner Weir; Fiscal Year: 2006
    ..Identifying such cell(s) would then direct focus on the expansion and differentiation of that cell type to a sustainable source of new beta cells. ..
  5. Phenotypic Analysis of Young and Old Beta Cells
    Susan Bonner Weir; Fiscal Year: 2005
    ..Another important outcome of this research should be valuable information about such practical questions as what will lead to successful long-term islet transplantation. ..
  6. MECHANISMS OF ISLET GROWTH AND DIFFERENTIATION
    Susan Bonner Weir; Fiscal Year: 1993
    ..This project should contribute to the understanding of the presumably complex orchestration of factors regulating the growth and differentiation of the pancreatic B-cell...
  7. MECHANISMS OF ISLET GROWTH AND DIFFERENTIATION
    Susan Bonner Weir; Fiscal Year: 1992
    ..This project should contribute to the understanding of the presumably complex orchestration of factors regulating the growth and differentiation of the pancreatic B-cell...