Project Abstracts - Enhancement Center

John Kaddis, PhD, City of Hope, Investigator

Start Date: September 15, 2014

 

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Abstract

The Human Islet Research Network (HIRN) was established to support innovative and collaborative research into how human beta cells are lost in type 1 diabetes (T1D), and to find pioneering strategies to protect and replace functional beta cell mass in humans. This Network consists of five consortia, each with a distinct focus complementary in scope, actively working to achieve this goal. The science brought to bear is multidisciplinary, technically challenging, and requires intensive efforts in order to make innovative and translational breakthroughs in preventing and curing T1D. To advance the work, this application establishes a Human Islet Research Enhancement Center (HIREC) to provide the administrative leadership, a centralized organizational infrastructure, an information technology platform, and a research dissemination engine to address the burgeoning needs of the HIRN for the next five years. The HIREC will replace and leverage the efforts and investments of the HIRN Coordinating and Bioinformatics Centers, which investigators in this proposal established in 2014. The overall objective of the HIREC is to cultivate and facilitate team science within HIRN. The following specific aims of this application are proposed to provide Meetings, Opportunities, Resources, and Exchange (MORE) to HIRN: 1) Provide research operations and organizational services to support scientific meetings, annual retreats, workshops, committees, working groups, and panels, 2) Facilitate and accelerate new research paths through funding opportunities and collaboration with other T1D and related communities, 3) Enhance a modern technology platform to provide and preserve access to HIRN materials, data, and other resources, using available or expanded vocabularies, ontologies, identifiers, and data formats, and 4) Catalyze collaboration and innovation in T1D research through the exchange of ideas, findings, and data generated in HIRN. Delivering MORE to HIRN will facilitate the ultimate goal of creating permanent preventive and curative therapies in T1D.

Publications

• Pericyte dysfunction and impaired vasomotion are hallmarks of islets during the pathogenesis of type 1 diabetes
• Enrichment of stem cell-derived pancreatic beta-like cells and controlled graft size through pharmacological removal of proliferating cells
• Senescence: a double-edged sword in beta-cell health and failure?
• Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes
• Generation of functional thymic organoids from human pluripotent stem cells
• Cell Replacement Therapy for Type 1 Diabetes Patients: Potential Mechanisms Leading to Stem-Cell-Derived Pancreatic β-Cell Loss upon Transplant
• Regulatory T cell homeostasis: Requisite signals and implications for clinical development of biologics
• DNA methylation Dependent Restriction of Tyrosine Hydroxylase Contributes to Pancreatic β-cell Heterogeneity
• The emerging role of regulatory cell-based therapy in autoimmune disease
• Human stem cell derived beta-like cells engineered to present PD-L1 improve transplant survival in NOD mice carrying human HLA class I
• Stem-Cell-Derived β-Like Cells with a Functional PTPN2 Knockout Display Increased Immunogenicity
• The dichotomous outcomes of TNFα signaling in CD4(+) T cells
• Yo-Yo Dieting: Mixed Messages for β-Cell Plasticity
• Stem cell-based multi-tissue platforms to model human autoimmune diabetes
• Editorial: alternative antigen processing and presentation in immune disorders
• Functional architecture of pancreatic islets identifies a population of first responder cells that drive the first-phase calcium response
• The Yin and Yang of Modulating β-Cell DNA Damage Response and Functional Mass
• Mitofusins Mfn1 and Mfn2 Are Required to Preserve Glucose- but Not Incretin-Stimulated β-Cell Connectivity and Insulin Secretion
• LGR4, a G Protein-Coupled Receptor With a Systemic Role: From Development to Metabolic Regulation
• Polycomb Repressive Complexes: Shaping Pancreatic Beta-Cell Destiny in Development and Metabolic Disease
• Pericyte Control of Blood Flow in Intraocular Islet Grafts Impacts Glucose Homeostasis in Mice
• Generation of human islet cell type-specific identity genesets
• Expanded LUXendin Color Palette for GLP1R Detection and Visualization In Vitro and In Vivo
• Emerging Diabetes Therapies: Bringing back the β-cells
• Limited extent and consequences of pancreatic SARS-CoV-2 infection
• From the dish to humans: A stem cell recipe for success
• Improving the Prediction of Type 1 Diabetes Across Ancestries
• Cell maturation: Hallmarks, triggers, and manipulation
• Modeling human T1D-associated autoimmune processes
• CAR T-Cell Therapy: Is CD28-CAR Heterodimerization Its Achilles’ Heel?
• Use of Induced Pluripotent Stem Cells to Build Isogenic Systems and Investigate Type 1 Diabetes
• The Immunoregulatory Role of the Signal Regulatory Protein Family and CD47 Signaling Pathway in Type 1 Diabetes
• ENTPD3 Marks Mature Stem Cell Derived Beta Cells Formed by Self-Aggregation in Vitro
• Generation of functional human thymic cells from induced pluripotent stem cells
• Strategies for durable β cell replacement in type 1 diabetes
• Protecting Stem Cell Derived Pancreatic Beta-Like Cells From Diabetogenic T Cell Recognition
• From type 1 diabetes biology to therapy: The Human Islet Research Network
• Means, Motive, and Opportunity: Do Non-Islet-Reactive Infiltrating T Cells Contribute to Autoimmunity in Type 1 Diabetes?
• Deconstructing the Origins of Sexual Dimorphism in Sensory Modulation of Pancreatic β Cells
• DNA Methylation Patterning and the Regulation of Beta Cell Homeostasis
• In vitro generation of peri-islet basement membrane-like structures
• Proinsulin-Reactive CD4 T Cells in the Islets of Type 1 Diabetes Organ Donors
• Pancreatic beta cell autophagy is impaired in type 1 diabetes
• Functional Characterization of the Human Islet Microvasculature Using Living Pancreas Slices
• Image-based machine learning algorithms for disease characterization in the human type 1 diabetes pancreas
• SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 Are Expressed in the Microvasculature and Ducts of Human Pancreas but Are Not Enriched in β Cells
• Beta cell dysfunction in diabetes: the islet microenvironment as an unusual suspect
• Blood Flow in the Pancreatic Islet: Not so Isolated Anymore
• FMRP promotes RNA localization to neuronal projections through interactions between its RGG domain and G-quadruplex RNA sequences
• Islet pericytes convert into profibrotic myofibroblasts in a mouse model of islet vascular fibrosis
• Modeling Hypoxia-Induced Neuropathies Using a Fast and Scalable Human Motor Neuron Differentiation System
• Super-resolution microscopy compatible fluorescent probes reveal endogenous glucagon-like peptide-1 receptor distribution and dynamics
• Circulating unmethylated insulin DNA as a biomarker of human beta cell death: a multi-laboratory assay comparison
• Epigenetics and Type 2 Diabetes Risk
• A Versatile, Portable Intravital Microscopy Platform for Studying Beta-cell Biology In Vivo
• Crossreactive public TCR sequences undergo positive selection in the human thymic repertoire
• TRPV1 neurons regulate β-cell function in a sex-dependent manner
• Modifying Enzymes Are Elicited by ER Stress, Generating Epitopes That Are Selectively Recognized by CD4(+) T Cells in Patients With Type 1 Diabetes
• Hospital time prior to death and pancreas histopathology: implications for future studies
• Avidity and Bystander Suppressive Capacity of Human Regulatory T Cells Expressing De Novo Autoreactive T-Cell Receptors in Type 1 Diabetes
• Deciphering the Pathogenesis of Human Type 1 Diabetes (T1D) by Interrogating T Cells from the “Scene of the Crime”
• Narrowing in on the anti-β cell-specific T cells: looking ‘where the action is’
• Tissue distribution and clonal diversity of the T and B cell repertoire in type 1 diabetes
• Analysis of self-antigen specificity of islet-infiltrating T cells from human donors with type 1 diabetes