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Genomes and Genes | Gordon WeirSummaryAffiliation: Harvard University Country: USA Publications
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Publications
Cellular transplantation into lymph nodes may not be such a crazy ideaGordon C Weir
Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA 02215, USA Department of Medicine, Harvard Medical School, Boston, MA 02115, USA Electronic address
Cell Stem Cell 11:587-8. 2012..A study published in Nature Biotechnology by Komori and colleagues (Komori et al., 2012) has identified the surprising potential of lymph nodes as sites for cellular transplants...
Subpopulations of GFP-marked mouse pancreatic β-cells differ in size, granularity, and insulin secretionHitoshi 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...- Single pancreatic beta cells co-express multiple islet hormone genes in miceH Katsuta
Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, MA 02215, USA
Diabetologia 53:128-38. 2010..We examined whether beta cells express other genes encoding islet hormones... 
Beta-cell adaptation and decompensation during the progression of diabetesG C Weir
Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
Diabetes 50:S154-9. 2001..Arguments are developed that the beta-cell changes found in diabetes are better correlated with increased glucose levels than with non-esterified fatty acid levels, thus supporting the importance of glucose toxicity...- Can we make surrogate beta-cells better than the original?Gordon C Weir
Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA
Semin Cell Dev Biol 15:347-57. 2004..Bioengineering can be used to improve secretory performance and strengthen cells to better withstand the challenges of transplantation. Strategies include protection against hypoxia, inflammation, and immune attack... - A dominant role for glucose in beta cell compensation of insulin resistanceGordon 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... - Five stages of evolving beta-cell dysfunction during progression to diabetesGordon 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... - Towards better understanding of the contributions of overwork and glucotoxicity to the beta-cell inadequacy of type 2 diabetesG C Weir
Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
Diabetes Obes Metab 11:82-90. 2009.... - Finally! A human pancreatic β cell lineGordon 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.... - Survival and maturation of microencapsulated porcine neonatal pancreatic cell clusters transplanted into immunocompetent diabetic miceAbdulkadir 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... - Exendin-4 uses Irs2 signaling to mediate pancreatic beta cell growth and functionSunmin Park
Howard Hughes Medical Institute, Division of Endocrinology, Department of Medicine, Children s Hospital Boston, MA 02215, USA
J Biol Chem 281:1159-68. 2006.... - p38 MAPK is a major regulator of MafA protein stability under oxidative stressTakuma 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... - New sources of pancreatic beta-cellsSusan 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... - Exercise induces hypoglycemia in rats with islet transplantationAbdulkadir Omer
Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, Massachusetts, USA
Diabetes 53:360-5. 2004..C-peptide and glucagon responses to exercise were very different in rats with transplanted islets compared with controls. This islet dysfunction led to exercise-induced hypoglycemia... - Suppression of beta cell energy metabolism and insulin release by PGC-1alphaJ 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... - Islet transplantation: progress and challengeJason L Gaglia
Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
Arch Med Res 36:273-80. 2005..In this review, we describe details of the evolution of modern islet transplantation and provide insight into ongoing clinical and basic research efforts to overcome current obstacles for this promising therapy... - Overexpression of c-Myc in beta-cells of transgenic mice causes proliferation and apoptosis, downregulation of insulin gene expression, and diabetesD Ross Laybutt
Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, Massachusetts, USA
Diabetes 51:1793-804. 2002.... - Bone marrow or foetal liver cells fail to induce islet regeneration in diabetic Akita miceTomoyuki 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... - Long-term normoglycemia in rats receiving transplants with encapsulated isletsAbdulkadir Omer
Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
Transplantation 79:52-8. 2005..Smaller capsules made of alginate cross-linked with barium appear to provide better stability and may be a useful strategy for use in larger recipients... - Normal relationship of beta- and non-beta-cells not needed for successful islet transplantationAileen 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... - Effects of insulin replacements, inhibitors of angiotensin, and PKCbeta's actions to normalize cardiac gene expression and fuel metabolism in diabetic ratsEmi Arikawa
Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
Diabetes 56:1410-20. 2007..Thus, PKCbeta or ACE inhibitors may ameliorate cardiac metabolism and function in diabetes partly by normalization of fuel metabolic gene expression directly in the myocardium... - In vivo imaging of autologous islet grafts in the liver and under the kidney capsule in non-human primatesZdravka Medarova
Department of Radiology, Molecular Imaging Laboratory, MGH MIT HMS Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital Harvard Medical School, Boston, MA 02129, USA
Transplantation 87:1659-66. 2009..The potential translation of these findings to the clinical situation requires validation of our methodology in a non-human primate model, which we have now carried out in baboons (Papio hamadryas) and reported here... - Critical reduction in beta-cell mass results in two distinct outcomes over time. Adaptation with impaired glucose tolerance or decompensated diabetesD 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... - Development and retroviral transduction of porcine neonatal pancreatic islet cells in monolayer cultureKrystyna 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... - Involvement of protein kinase C beta 2 in c-myc induction by high glucose in pancreatic beta-cellsHideaki 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... - Prediction of marginal mass required for successful islet transplantationKlearchos K Papas
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
J Invest Surg 23:28-34. 2010..Because human clinical islet preparations in a previous study had OCR/DNA... - Genetic regulation of metabolic pathways in beta-cells disrupted by hyperglycemiaD 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... - Induced pluripotent stem cells generated without viral integrationMatthias Stadtfeld
Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, 185 Cambridge Street, Boston, MA 02114, USA
Science 322:945-9. 2008..Adenoviral reprogramming may provide an improved method for generating and studying patient-specific stem cells and for comparing embryonic stem cells and iPS cells... - Importance of hyperglycemia on the primary function of allogeneic islet transplantsLeila Makhlouf
Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA
Transplantation 76:657-64. 2003..CONCLUSIONS: This study demonstrates that severe hyperglycemia impairs islet allograft function in BALB/c and NOD mice and that successful islet allotransplantation depends on the degree of hyperglycemia in the recipient... - Induction of Mad expression leads to augmentation of insulin gene transcriptionGiovanni Patanè
Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, MA 02215, USA
Biochem Biophys Res Commun 303:1199-208. 2003..Such regulation of insulin expression by Mad with modulation of PDX-1 expression and DNA binding activity could offer useful therapeutic and/or experimental tools to promote insulin production in appropriate cell types... - Induction of c-Myc expression suppresses insulin gene transcription by inhibiting NeuroD/BETA2-mediated transcriptional activationHideaki 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... - Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expressionHideaki 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... - Induced ICER Igamma down-regulates cyclin A expression and cell proliferation in insulin-producing beta cellsAkari 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... - Differentiation of affinity-purified human pancreatic duct cells to beta-cellsShigeru 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... - PDX-1 protein containing its own antennapedia-like protein transduction domain can transduce pancreatic duct and islet cellsHirofumi Noguchi
Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
Diabetes 52:1732-7. 2003.... - Insulin regulates SOCS2 expression and the mitogenic effect of IGF-1 in mesangial cellsKeiji Isshiki
Research Division, Joslin Diabetes Center, One Joslin Place, Harvard Medical School, Boston, Massachusetts 02215, USA
Kidney Int 74:1434-43. 2008..Insulin deficiency may contribute to the mesangial expansion found in diabetes through reduced STAT5/SOCS2 expression... - Adult mouse intrahepatic biliary epithelial cells induced in vitro to become insulin-producing cellsMasaki 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... - NeuroD and reaggregation induce beta-cell specific gene expression in cultured hepatocytesShigeru 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... - Increased expression of antioxidant and antiapoptotic genes in islets that may contribute to beta-cell survival during chronic hyperglycemiaD 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... - Gene expression profiles of Beta-cell enriched tissue obtained by laser capture microdissection from subjects with type 2 diabetesLorella 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... - Pig islet xenograft rejection in a mouse model with an established human immune systemNoriko Tonomura
Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
Xenotransplantation 15:129-35. 2008..A better understanding of the human immune response to pig islets would help develop effective strategies for preventing graft rejection... - Transplantation of islets transduced with CTLA4-Ig and TGFbeta using adenovirus and lentivirus vectorsJustin 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.... - Downregulation of GLP-1 and GIP receptor expression by hyperglycemia: possible contribution to impaired incretin effects in diabetesGang 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... - Evidence for a role of the ubiquitin-proteasome pathway in pancreatic isletsMaria D Lopez-Avalos
Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
Diabetes 55:1223-31. 2006.... - Macrophage depletion improves survival of porcine neonatal pancreatic cell clusters contained in alginate macrocapsules transplanted into ratsAbdulkadir Omer
Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
Xenotransplantation 10:240-51. 2003..CONCLUSION: We conclude that depletion of peritoneal macrophages with clodronate liposomes improve the survival of macroencapsulated NPCCs... - A model for diabetic nephropathy: advantages of the inducible cAMP early repressor transgenic mouse over the streptozotocin-induced diabetic mouseAkari Inada
SSP Stem Cell Unit, Kyushu University Graduate School of Medicine, Fukuoka, Japan
J Cell Physiol 215:383-91. 2008..Thus, ICER Igamma Tg mouse has advantages for examining diabetic renal disease, and offers unique and very different perspectives compared to STZ model... - Beta-cell precursors--a work in progressGordon C Weir
Nat Biotechnol 22:1095-6. 2004 - The Nkx6.1 homeodomain transcription factor suppresses glucagon expression and regulates glucose-stimulated insulin secretion in islet beta cellsJonathan C Schisler
Department of Pharmacology, Sarah W Stedman Nutrition and Metabolism Center, Durham, NC 27704, USA
Proc Natl Acad Sci U S A 102:7297-302. 2005..1 mRNA in primary rat islets was accompanied by a significant decrease in GSIS relative to control cells. In sum, our studies have revealed roles for Nkx6.1 in suppression of glucagon expression and control of GSIS in islet beta cells... - Establishment of a diabetic mouse model with progressive diabetic nephropathyAkari 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... - The HNF-1 target collectrin controls insulin exocytosis by SNARE complex formationKenji Fukui
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita Osaka 565 0871, Japan
Cell Metab 2:373-84. 2005..Therefore, collectrin is a regulator of SNARE complex function, which thereby controls insulin exocytosis... - GLP-1/exendin-4 facilitates beta-cell neogenesis in rat and human pancreatic ductsGang Xu
Diabetes Res Clin Pract 73:107-10. 2006 - Survival of microencapsulated adult pig islets in mice in spite of an antibody responseValerie F Duvivier-Kali
Diabetes and Obesity Unit, Sanofi Synthelabo, Rueil Malmaison, France
Am J Transplant 4:1991-2000. 2004..In conclusion, alginate capsules can prolong the survival of adult pig islets transplanted into diabetic mice for up to 190 days, even in the presence of an antibody response... - Islet transplantation under the kidney capsule corrects the defects in glycogen metabolism in both liver and muscle of streptozocin-diabetic ratsMargherita Matarazzo
Department of Internal Medicine and Cardiovascular Sciences, University of Federico II School of Medicine, Napoli, Italy
Cell Transplant 11:103-12. 2002..In conclusion, islet transplantation under the kidney capsule corrects the diabetes-induced abnormalities in glycogen and glucose-6-phosphate content and glycogen synthase activity in both liver and skeletal muscle... - Mechanism of insulin gene regulation by the pancreatic transcription factor Pdx-1: application of pre-mRNA analysis and chromatin immunoprecipitation to assess formation of functional transcriptional complexesTessy Iype
Department of Internal Medicine and the Diabetes Center, University of Virginia, Charlottesville, Virginia 22908, USA
J Biol Chem 280:16798-807. 2005..This complex leads to enhancement of elongation by the basal transcriptional machinery... - A stirred microchamber for oxygen consumption rate measurements with pancreatic isletsKlearchos K Papas
Department of Chemical Engineering, Massachusetts Institute of Technology, 25 Ames St, Cambridge, Massachusetts 02139, USA
Biotechnol Bioeng 98:1071-82. 2007....
Research Grants
- DIABETES AND ENDOCRINOLOGY RESEARCH CENTERGordon Weir; Fiscal Year: 2007..The Enrichment Program continues to enhance the research environment for students, post-doctoral fellows and investigators by supporting a valuable array of academic exercises and visiting speakers. ..
- Islet Transplantation - Protection by ImmunobarriersGordon Weir; Fiscal Year: 2007..This work should serve as a guide for the encapsulation and transplantation of xenogeneic islets cells or insulin-producing cells that should eventually be produced from precursor/stem cells. ..
- ISLET TRANSPLANTATION-- PROTECTION BY IMMUNOBARRIERSGordon Weir; Fiscal Year: 2004..The other is to engineer the islets to secrete peptides, in particular CTLA4 and TGF-p, that may modulate the immune attack surrounding the capsules. ..
- ISLET TRANSPLANTATION--FUNCTION AND ANGIOGENESISGordon Weir; Fiscal Year: 1999..IRAP will be overexpressed in beta cells by the genetic manipulations of transfection and the production of transgenic mice to determine if transplanted islets can be protected at the site of attack from immune injury. ..
- DIABETES AND ENDOCRINOLOGY RESEARCH CENTERGordon Weir; Fiscal Year: 2007..The Enrichment Program continues to enhance the research environment for students, post-doctoral fellows and investigators by supporting a valuable array of academic exercises and visiting speakers. ..