Publications - user -
Researchers at the University of Alberta
AM James Shapiro
Post-transplant characterization of long-term functional hESC-derived pancreatic endoderm grafts Pepper AR et al Diabetes 65:953, 2019
Improved islet recovery and efficacy through co-culture and co-transplantation of islets with human adipose-derived mesenchymal stem cells Gamble A et al PLoS One 13:e0206449, 2018
BMX-001, a novel redox-active metalloporphyrin, improves islet function and engraftment in a murine transplant model Bruni A et al Am J Transplant 18:1879, 2018
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Transplantation of human pancreatic endoderm cells reverses diabetes post transplantation in a prevascularized subcutaneous site Pepper AR et al Stem Cell Rep 8:1689, 2017
Long-term function and optimization of mouse and human islet transplantation in the subcutaneous device-less site Pepper A et al Islets 8:186, 2016
A novel pre-vascularized subcutaneous site safely accommodates stem cell derived therapies for treating diabetes Gala-Lopez B et al J Stem Trans Biol 2:270000107, 2016
Lung-derived microscaffolds facilitate diabetes reversal after mouse and human intraperitoneal islet transplantation Abualhassan N et al PLoS One 1:e0156053, 2016
Anti-aging glycopeptide protects human islets against tacrolimus-related injury and facilitates engraftment in mice Gala-Lopez BL et al Diabetes 65:451, 2016
A prevascularized subcutaneous 'Device-Less' site for islet and cellular transplantation Pepper A et al Nat Biotechnol 33:518, 2015
Glutathione ethyl ester supplementation during pancreatic islet isolation improves viability and transplant outcomes in a murine marginal islet mass model Raposo do Amaral AS et al PLoS One 8:e55288, 2013
Anakinra potentiates the protective effects of etanercept in transplantation of marginal mass human islets in immunodeficient mice McCall M et al Am J Transplant 12:322, 2012
AEB071 (sotrastaurin) does not exhibit toxic effects on human islets in vitro, nor after transplantation into immunodeficient mice Merani S et al Islets 3:338, 2011
The caspase inhibitor IDN-6556 (PF3491390) improves marginal mass engraftment after islet transplantation in mice McCall M et al Surgery 150:48, 2011
Human islet distribution program for basic research at a single center Kin T et al Transplant Proc 43:3195, 2011
Liraglutide, a long-acting human glucagon-like peptide 1 analogue, improves human islet survival in culture Toso C et al Transplant Int 23:259, 2010
The caspase selective inhibitor EP1013 augments human islet graft function and longevity in marginal mass islet transplantation in mice Emamaullee JA et al Diabetes 57:1556, 2008
Patrick MacDonald
Ca2+ oscillations, waves, and networks in islets from human donors with and without type 2 diabetes Gosak M and Yan-Do R et al bioRxiv 2021 https://doi.org/10.1101/2021.12.08.471749
Heterogenous impairment of α-cell function in type 2 diabetes is linked to cell maturation state Dai X-Q et al Cell Metab 34:256, 2022
A role for PKD1 in insulin secretion downstream of P2Y1 receptor activation in mouse and human islets Khan S et al Physiol Rep 7:e14250, 2019
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Kv2.1 clustering contributes to insulin exocytosis and rescues human β-cell dysfunction Fu J et al Diabetes 66:1890, 2017
STEAP4 expression in human islets is associated with differences in body mass index, sex, HbA1c, and inflammation Gordon HM et al Endocrine 56:528, 2017
SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells Ferdaoussi M et al Sci Rep 7:248, 2017
PI3 kinases p110α and PI3K-C2β negatively regulate cAMP via PDE3/8 to control insulin secretion in mouse and human islets Kolic J et al Mol Metab 5:459, 2016
A glycine-insulin autocrine feedback loop enhances insulin secretion from human β-cells and is impaired in type 2 diabetes Yan-Do R et al Diabetes 65:2311, 2016
Interleukin-1 signaling contributes to acute islet compensation Hajmrle C et al JCI Insight 1:e86055, 2016
Research-focused isolation of human islets from donors with and without diabetes at the Alberta Diabetes Institute IsletCore Lyon J et al Endocrinology 157:560, 2016
TCF1 links GIPR signaling to the control of beta cell function and survival Campbell JE et al Nat Med 22:84, 2016
Rp-cAMPS prodrugs reveal the cAMP dependence of first-phase glucose-stimulated insulin secretion Schwede F and Chepurny OG et al Mol Endocrinol 29:988, 2015
Transcript expression data from human islets links regulatory signals from genome-wide association studies for type 2 diabetes and glycemic traits to their downstream effectors van de Bunt M and Manning Fox JE et al PLoS Genet 11:e1005694, 2015
Isocitrate-to-SENP1 signaling amplifies insulin secretion and rescues dysfunctional beta cells Ferdaoussi M and Dai X et al J Clin Invest 125:3847, 2015
Human islet function following 20 years of cryogenic biobanking Manning Fox JE et al Diabetologia 58:1053, 2015
Insulin secretion induced by glucose-dependent insulinotropic polypeptide requires PI3 kinase-γ in rodent and human β cells Kolic J et al J Biol Chem 289:32109, 2014
SUMOylation protects against IL-1β-induced apoptosis in INS-1 832/13 and human islets Hajmrle C et al Am J Physiol Endocrinol Metab 307:E664, 2014
SUMO1 enhances cAMP-dependent exocytosis and glucagon secretion from pancreatic α-cells Dai XQ et al J Physiol 592:3715, 2014
Triton X-100 inhibits L-type voltage-operated calcium channels Narang D et al Can J Physiol Pharmacol 91:316, 2013
Distinct and opposing roles for the phosphatidylinositol 3-OH kinase catalytic subunits p110α and p110β in the regulation of insulin secretion from rodent and human beta cells Kolic J et al Diabetologia 56:1339, 2013
Functional plasticity of the human infant beta-cell exocytotic phenotype Manning Fox JE et al Endocrinology 154:1392, 2013
The voltage-dependent potassium channel subunit Kv2.1 regulates insulin secretion from rodent and human islets independently of its electrical function Dai XQ et al Diabetologia 55:1709, 2012
SUMOylation regulates insulin exocytosis downstream of secretory granule docking in rodents and humans Dai XQ et al Diabetes 60:838, 2011
Voltage-dependent K+ channels are positive regulators of alpha cell action potential generation and glucagon secretion in mice and humans Spigelman AF et al Diabetologia 53:1917, 2010
Inhibition of beta-cell sodium-calcium exchange enhances glucose-dependent elevations in cytoplasmic calcium and insulin secretion Hamming KSC et al Diabetes 59:1686, 2010
Kiss-and-run exocytosis and fusion pores of secretory vesicles in human β-cells Hanna ST et al Pflugers Arch 457:1343, 2009
SUMOylation regulates Kv2.1 and modulates pancreatic β-cell excitability Dai XQ et al J Cell Sci 122:775, 2009
Insulin granule recruitment and exocytosis is dependent on p110γ in insulinoma and human β-cells Pigeau GM et al Diabetes 58:2084, 2009
Greg Korbutt
Identification and differentiation of PDX-1 beta-cell progenitor within human pancreatic epithelium Seeberger et al World J Diabetes 5:59, 2014
Immunohistochemical characterization of insulin, glucagon, PDX1, SOX17 and NGN3 expression in human fetal pancreatic development Anderson SJ et al J Stem Cell Res Ther 3:4, 2013
Human mesenchymal stem cells protect islets from pro-inflammatory cytokines Yeung TY et al PLoS One 7:e38189, 2012
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Epithelial cells within the human pancreas do not coexpress mesenchymal antigens: epithelial-mesenchymal transition is an artifact of cell culture Seeberger KL et al Lab Invest 89:110, 2009
Matthias Braun
Autocrine activation of P2Y1 receptors couples Ca2+ influx to Ca2+ release in human pancreatic beta cells Khan S and Yan-Do R et al Diabetologia 57:2525, 2014
Peter Light
Human islets contain a subpopulation of glucagon-like peptide-1 secreting α cells that is increased in type 2 diabetes Campbell SA et al Mol Metab 39:101014, 2020
The DPP4 inhibitor sitagliptin increases active GLP-1 levels from human islets and may increase islet cell survival prior to transplantation Campbell SA et al OBM Transplantation 3:14, 2019
Andrew Pepper
Nanothin onformal coating with poly(N-vinylpyrrolidone) and tannic acid (PVPON/TA) preserves murine and human pancreatic islets function Polishevska K et al Pharmaceutics 15:1137, 2023
Researchers National / International
Hitoshi Okochi (National Center for Global Health and Medicine, Japan)
Encapsulated human islets in alginate fiber maintain long-term functionality Nishida J et al Endocr J. EJ23-0474 2023
Robert Screaton (Sunnybrook Research Institute, Canada)
Slicing of the G-protein coupled receptor 3-salt inducible kinase 2 pathway in human β cell proliferation Iorio C et al Commun Biol 4:907, 2021
High-throughput functional genomics identifies regulators of primary human beta cell proliferation Robitaille K et al J Biol Chem 29:4614, 2016
Nika Danial (Dana-Farber Cancer Institute, USA)
Glucose metabolism and pyruvate carboxylase enhance glutathione synthesis and restrict oxidative stress in beta-cells Fu A et al Cell Rep 37:110037, 2021
Glucose-dependent partitioning of arginine to the urea cycle protects β-cells from inflammation Fu A et al Nat Metab 2:432, 2020
Xiaojuan Chen (Columbia University, USA)
Abnormal regulation of glucagon secretion by human islet alpha cells in the absence of beta cells Liu W et al EBioMedicine 50:306, 2019
Mark Ungrin (University of Calgary, Canada)
Bioengineered human pseudoislets form efficiently from donated tissue, compare favourably with native islets in vitro and restore normoglycemia in mice Yu Y et al Diabetologia 61:2016, 2018
Adrian Teo (Institute of Molecular and Cell Biology, Singapore)
Metformin perturbs pancreatic differentiation from human embryonic stem cells Nguyen L et al Diabetes 70:1689, 2021
Multimodal imaging probe development for pancreatic beta-cells: from fluorescence to PET Kang NY et al J Am Chem Soc 142:3430, 2020
Human islet isolation and distribution efforts for clinical and basic research Ng NHJ et al OBM Transplantation 3:31, 2019
Single cell analyses of human islet cells reveal de-differentiation signatures Teo AKK et al Cell Death Discov 4:14, 2018
Francis Lynn (University of British Columbia, Canada)
Type2 diabetes susceptibility gene GRK5 regulates physiological pancreatic beta-cell proliferation via phosphorylation of HDAC5 Sasaki S et al iScience 26, 107311, 2023
Calcium-dependent transcriptional changes in human pancreatic islet cells reveal functional diversity in islet cell subtypes Yoon JS et al Diabetologia 2022 Retracted on August 04, 2023
Neuronal PAS domain protein 4 (NPAS4) suppression of oxygen sensing optimizes metabolism during excitation of neuroendocrine cells Sabatini PV and Speckmann T et al Cell Rep 22:163, 2018
Jun Shirakawa (Gunma University, Japan)
E2F1 transcription factor mediates a link between fat and islets to promote β-cell proliferation in response to acute insulin resistance Shirakawa J et al Cell Rep 41:111436, 2022
Uncoupling protein 2 and aldolase B impact insulin release by modulating mitochondrial function and Ca2+ release from the ER Inoue R et al iScience 25:104603, 2022
Imeglimin ameliorates β-cell apoptosis by modulating the endoplasmic reticulum homeostasis pathway Li J et al Diabetes 71:424, 2021
Luseogliflozin increases beta cell proliferation through humoral factors that activate an insulin receptor- and IGF1 receptor-independent pathway Shirakawa J and Tajima K et al Diabetologia 63:577, 2020
Hirofumi Noguchi (University of the Ryukyus, Japan)
Induction of expandable tissue-specific progenitor cells from human pancreatic tissue through transient expression of defined factors Noguchi H et al Mol Ther Methods Clin Dev 13:243, 2019
Role of EGR1 on pancreatic endoderm differentiation Tsugata T et al Cell Med 10:2155179017733177, 2018
Potential factors for the differentiation of ES/iPS cells into insulin-producing cells Tsugata T et al Cell Med 7:83, 2015
Susumu Eguchi (Nagasaki University, Japan)
An engineered cell sheet composed of human islets and human fibroblast, bone marrow-derived mesenchymal stem cells, or adipose-derived mesenchymal stem cells: An in vitro comparison study Imamura H et al Islets 10:e1445948, 2018
Human fibroblast sheet promotes human pancreatic islet survival and function in vitro Matsushima H et al Cell Transplant 25:1525,2016
Atsushi Miyajima (University of Tokyo, Japan)
CD82 is a marker to isolate β cell precursors from human iPS cells and plays a role for the maturation of β cells Watanabe A et al Sci Rep 11:9530, 2021
Hideki Taniguchi / Takanori Takebe (Yokohama City University, Japan)
Self-condensation culture enables vascularization of tissue fragments for efficient therapeutic transplantation Takahashi Y et al Cell Rep 23:1620, 2018
Kazuo Ohashi (Tokyo Women's Medical University, Japan)
Quality of air-transported human islets for single islet cells preparations Yamashita S et al Cell Med 6:33, 2013
Klearchos Papas (University of Arizona, USA)
Human islet viability and function is maintained during high density shipment on silicone rubber membrane vessels Kitzmann JP et al Transplant Proc 46:1989, 2014
Ho-Wook Jun (University of Alabama, USA)
Encapsulation of human islets using a biomimetic self-assembled nanomatrix gel for protection against cellular inflammatory responses Hwang PTJ et al ACS Biomater Sci Eng 3:2110, 2017
Holger Russ (University of Colorado, USA)
ENTPD3 marks mature stem cell–derived β-Cells formed by self-aggregation in vitro Docherty FM et al Diabetes 70:2554, 2021
Craig Nunemaker (Ohio University, USA)
The capacity to secrete insulin is dose-dependent to extremely high glucose concentrations: a key role for adenylyl cyclase Gerber KM and Whitticar NB et al Metabolites 11:401, 2021
Michael Wheeler (University of Toronto, Canada)
γ‐aminobutyric acid stimulates β‐cell proliferation through the mTORC1/p70S6K pathway, an effect amplified by Ly49, a novel γ‐aminobutyric acid type A receptor positive allosteric modulator Untereiner A et al Diabetes Obes Metab 22:2021, 2020
The magnesium transporter NIPAL1 is a pancreatic islet-expressed protein that conditionally impacts insulin secretion Manialawy et al J Biol Chem 295:9879, 2020
GABA promotes β-cell proliferation, but does not overcome impaired glucose homeostasis associated with diet-induced obesity Untereiner A et al FASEB J 33:3968, 2019
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Elevated medium chain-acylcarnitines are associated with gestational diabetes, and early progression to type-2 diabetes, and induce pancreatic β-Cell dysfunction Batchuluun B et al Diabetes 67:885, 2018
Synthesis and characterization of urofuranoic acids: in vivo metabolism of 2-(2-carboxyethyl)-4-methyl-5-propylfuran-3-carboxylic acid (CMPF) and effects on in vitro insulin secretion Nagy E et al J Med Chem 60:1860, 2017
A novel GLP-1 receptor interacting protein ATP6ap2 regulates insulin secretion in pancreatic beta cells Dai FF et al J Biol Chem 290:25045, 2016
An abbreviated protocol for in vitro generation of functional human embryonic stem cell-derived beta-like cells Massumi M et al PLoS One 11:e0164457, 2016
Rapid elevation in CMPF may act as a tipping point in diabetes development Liu Y and Prentice KJ et al Cell Rep 14:2889, 2016
Characterization of Zinc Influx Transporters (ZIPs) in Pancreatic Beta Cells: Roles in Regulating Cytosolic Zinc Homeostasis and Insulin Secretion Liu Y et al J Biol Chem 290:18757, 2015
The furan fatty acid metabolite CMPF Is elevated in diabetes and induces beta cell dysfunction Prentice KJ et al Cell Metab 19:653, 2014
UCP2 regulates the glucagon response to fasting and starvation Allister EM et al Diabetes 62:1623, 2013
Effects of high-fat diet feeding on Znt8-null mice: differences between beta-cell and global knockout of Znt8 Hardy AB et al Am J Physiol Endocrinol Metab 302:E1084, 2012
The functional and molecular characterisation of human embryonic stem cell-derived insulin-positive cells compared with adult pancreatic beta cells Basford CL et al Diabetologia 55:358, 2012
Beta-cell uncoupling protein 2 regulates reactive oxygen species production, which influences both insulin and glucagon secretion Robson-Doucette CA et al Diabetes 60:2710, 2011
The adult mouse and human pancreas contain rare multipotent stem cells that express insulin Smukler SR et al Cell Stem Cell 8:281, 2011
Beta cell-specific Znt8 deletion in mice causes marked defects in insulin processing, crystallisation and secretion Wijesekara N et al Diabetologia 53:1656, 2010
Ex vivo transcriptional profiling of human pancreatic islets following chronic exposure to monounsaturated fatty acids Bikopoulos G et al J Endocinol 196:455, 2009
Characterization of ERG K+ channels in alpha and beta cells of mouse and human islets Hardy AB et al J Biol Chem 284:30441, 2009
Andrew Stewart (Icahn School of Medicine at Mount Sinai, USA)
Disrupting the DREAM complex enables proliferation of adult human pancreatic beta cells Wang P et al J Clin Invest 32:e157086, 2022
GLP-1 receptor agonists synergize with DYRK1A inhibitors to potentiate functional human beta cell regeneration Ackeifi C and Wang P et al Sci Transl Med 12:eaaw9996, 2020
Combined inhibition of DYRK1A, SMAD, and trithorax pathways synergizes to induce robust replication in adult human beta cells Wang P and Karakose E et al Cell Metab 29:638, 2019
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Cell-based methods to identify inducers of human pancreatic beta-cell proliferation Ackeifi CA et al Phenotyping Screening: Methods and Protocols, Methods in Molecular Biology vol 1787, 2018
Insights into beta cell regeneration for diabetes via integration of molecular landscapes in human insulinomas Wang H et al Nat Commun 8:767, 2017
Augmented Stat5 signaling bypasses multiple impediments to lactogen-mediated proliferation in human beta cells Chen H et al Diabetes 64:3784, 2015
A high-throughput chemical screen reveals that harmine-mediated inhibition of DYRK1A increases human pancreatic beta cell replication Wang P et al Nat Med 21:383, 2015
A human pancreatic beta cell G1/S molecule cell cycle atlas Fiaschi-Taesch NM et al Diabetes 62:2450, 2013
Cytoplasmic-nuclear trafficking of G1/S cell cycle molecules and adult human beta cell replication: a revised model of human beta cell G1/S control Fiaschi-Taesch NM et al Diabetes 62:2460, 2013
Regulated and reversible induction of adult human β-cell replication Takane KK et al Diabetes 61:418, 2012
cMyc is a principal upstream driver of beta-cell proliferation in rat insulinoma cell lines and is an effective mediator of human beta-cell replication Karslioglu E et al Mol Endocrinol 25:1760, 2011
Yuval Dor (Hebrew University of Jerusalem, Israel)
DNA methylation-based assessment of cell composition in human pancreas and islets Drawshy et al Diabetes 73:554, 2024
A DNA methylation atlas of normal human cell types Loyfer N et al Nature 613:355, 2023
Islet cells share promoter hypomethylation independently of expression, but exhibit cell-type-specific methylation in enhancers Neiman D and Moss J et al Proc Natl Acad Sci USA 114:13525, 2017
p16Ink4a-induced senescence of pancreatic beta cells enhances insulin secretion Helman A et al Nat Med 22:412, 2016
Recognition and killing of human and murine pancreatic beta cells by the NK receptor NKp46 Gur C et al J Immunol 187:3096, 2011
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Glucose regulates cyclin D2 expression in quiescent and replicating pancreatic β-cells through glycolysis and calcium channels Salpeter SJ et al Endocrinology 152:2589, 2011
Vincent Poitout (University of Montreal, Canada)
Beta-cell mass expansion during puberty involves serotonin signaling and determines glucose homeostasis in adulthood Castell A-L et al JCI Insight 7:e160854, 2022
Pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of Langerhans Maachi H et al Sci Rep 11:11283, 2021
Glucose and fatty acids synergistically and reversibly promote beta cell proliferation in rats Moullé VS et al Diabetologia 60:879, 2017
The regulator of G-protein signaling RGS16 promotes insulin secretion and β-cell proliferation in rodent and human islets Vivot K et al Mol Metab 5:988, 2016
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Epidermal growth factor receptor signaling promotes pancreatic β-cell proliferation in response to nutrient excess in rats through mTOR and FOXM1 Zarrouki B et al Diabetes 63:982, 2014
Glucose activates free fatty acid receptor 1 gene transcription via phosphatidylinositol-3-kinase-dependent O-GlcNAcylation of pancreas-duodenum homeobox-1 Kebede M et al Proc Natl Acad Sci USA 109:2376, 2012
Lipopolysaccharides impair insulin gene expression in isolated islets of Langerhans via toll-like receptor-4 and NF-κB signalling Amyot J et al PLoS One 7:e36200, 2012
Discovery of novel glucose-regulated proteins in isolated human pancreatic islets using LC-MS/MS-based proteomics Schrimpe-Rutledge AC et al J Proteome Res 11:3520, 2012
Guy Rutter (Imperial College, London, UK)
Glucose-dependent miR-125b is a negative regulator of β-cell function Cheung R and Pizza G et al Diabetes 71: 1525, 2022
Leader β-cells coordinate Ca2+ dynamics across pancreatic islets in vivo Salem V et al Nature Metab 1:615, 2019
The effects of kisspeptin on β-cell function, serum metabolites and appetite in humans Izzi-Engbeaya C and Comninos AN et al Diabetes Obes Metab 20:2800, 2018
Targeting GLP-1 receptor trafficking to improve agonist efficacy Jones B et al Nat Commun 9:1602, 2018
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A targeted RNAi screen identifies endocytic trafficking factors that control GLP-1 receptor signaling in pancreatic beta cells Buenaventura T et al Diabetes 67:385, 2018
MiR-184 expression is regulated by AMPK in pancreatic islets Martinez-Sanchez A et al FASEB J 32:2587, 2018
Sorcin links pancreatic β cell lipotoxicity to ER Ca2+ stores Marmugi A et al Diabetes 65:1009, 2016
ADCY5 couples glucose to insulin secretion in human islets Hodson DJ et al Diabetes 63:3009, 2014
Optical control of insulin release using a photoswitchable sulfonylurea Broichhagen J et al Nat Commun 5:5116, 2014
Fred Levine (Burnham Institute for Medical Research, USA)
Id3 upregulates BrdU incorporation associated with a DNA damage response, not replication, inhuman pancreatic β-cells Lee SH et al Islets 3:358, 2011
The Id3/E47 axis mediates cell-cycle control in human pancreatic ducts and adenocarcinoma Lee SH et al Mol Cancer Res 9:782, 2011
CENP-A, a protein required for chromosome segregation in mitosis, declines with age in islet but not exocrine cells Lee S-H et al Aging 2:785, 2010
James Shaw (Newcastle University, UK)
Exendin-4 stimulates autophagy in pancreatic β-cells via the RAPGEF/EPAC-Ca2+-PPP3/calcineurin-TFEB axis Zummo FP et al Autophagy DOI: 10.1080/15548627.2021.1956123
Glucagon-like peptide 1 protects pancreatic β-cells from death by increasing autophagic flux and restoring lysosomal function Zummo FP et al Diabetes 66:1272, 2017
Sigal Shaklai (Tel Aviv Sourasky Medical Center, Israel)
Estradiol 17-β induces pancreatic beta-cell proliferation through distinct estrogen receptors in a glucose dependent manner Shaklai S et al OBM Transplantation 3:11, 2019
Pancreatic beta-cell proliferation induced by estradiol-17β is Foxo1 dependent Shaklai S and Grafi-Cohen M et al Horm Metab Res 50: 485, 2018
Shimon Efrat (Tel Aviv University, Israel)
Redifferentiation of expanded human islet β cells by inhibition of ARX Friedman-Mazursjy O et al Sci Rep 6:20698, 2016
Pamela Itkin-Ansari (University of California, San Diego, USA)
The IRE1α/XBP1s pathway is essential for the glucose response and protection of β cells Hassler JR et al PLoS Biol 13:e1002277, 2015
Eduardo Mitrani (Hebrew University of Jerusalem, Israel)
Lung-derived microscaffolds facilitate diabetes reversal after mouse and human intraperitoneal islet transplantation Abualhassan N et al PLoS One 1:e0156053, 2016
Sasanka Ramanadham (University of Alabama, USA)
Coming soon
Heiko Lickert (German Center for Diabetes Research, Germany)
Coming soon