Barbara Davis Center for Childhood Diabetes
I am an associate professor at the Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Anschutz Medical Campus, School of Medicine. My long-term research interests developed under the tutelage of Dr. George S. Eisenbarth in clinical immunology and genetics of type 1 diabetes, celiac disease, Addison’s disease, autoimmune thyroid disease and others. My most recent investigations are directly connected in multiple clinical trials to understand the immunogenetics and immunopathogenesis of type 1 diabetes, including mechanistic study of immunotherapy and development of novel biomarkers and assays. Our recently identified new autoantibodies to extra-cellular epitopes of ZnT8 on β-cell surface opens a new avenue of investigation into the role of IAbs in β-cell autoimmunity development underlying T1D etiology and progression. My clinical immunology laboratory is currently the NIH/NIDDK designated North America Autoantibody/HLA Core laboratory for type 1 diabetes clinical trials. The laboratory, and in collaboration with others researcher, has developed islet autoantibody assays for IAA, GAD65A, IA-2A, and ZnT8A that are the current “gold standard” in clinical immunology. Over the past several years, we have developed, validated, and patented a new generation of autoantibody assay technology, an electrochemiluminescence (ECL) assay method for IAA and GADA assays characterized by higher sensitivity and disease specificity. With ECL assay platform, we have recently developed a multiplexed assay to combine multiple autoantibody assays in one single well fit for large scale screening. The multiplex ECL assay has successfully been used in current screening for type 1 diabetes and celiac disease in general population children. At our Center immunogenetic and state of the art autoantibody analysis are integrated into clinical care and clinical research with a large population of patients tested for thyroid, Addison’s, celiac disease, APS-1, and rheumatoid arthritis risk. We believe understanding the genetic determinants of the constellation of autoimmune disorders affecting our patients will inform our studies of each of component diseases and guide the development of preventive therapy.
A common nonsynonymous single nucleotide polymorphism in the SLC30A8 gene determines ZnT8 autoantibody specificity in type 1 diabetes.
Diabetes Oct, 2008 | Pubmed ID: 18591387
A report on the International Transglutaminase Autoantibody Workshop for Celiac Disease.
The American journal of gastroenterology Jan, 2009 | Pubmed ID: 19098864
SlC30A8 is a major target of humoral autoimmunity in type 1 diabetes and a predictive marker in prediabetes.
Annals of the New York Academy of Sciences Dec, 2008 | Pubmed ID: 19120307
Type 1 diabetes: chronic progressive autoimmune disease.
Novartis Foundation symposium , 2008 | Pubmed ID: 19203094
Homozygosity of the polymorphism MICA5.1 identifies extreme risk of progression to overt adrenal insufficiency among 21-hydroxylase antibody-positive patients with type 1 diabetes.
The Journal of clinical endocrinology and metabolism Nov, 2009 | Pubmed ID: 19820007
Triple chimeric islet autoantigen IA2-ZnT8WR to facilitate islet autoantibody determination.
Journal of immunological methods Feb, 2010 | Pubmed ID: 20035758
Additional autoimmune disease found in 33% of patients at type 1 diabetes onset.
Diabetes care May, 2011 | Pubmed ID: 21430083
Human type 1 diabetes is associated with T cell autoimmunity to zinc transporter 8.
Journal of immunology (Baltimore, Md. : 1950) May, 2011 | Pubmed ID: 21471440
Age of islet autoantibody appearance and mean levels of insulin, but not GAD or IA-2 autoantibodies, predict age of diagnosis of type 1 diabetes: diabetes autoimmunity study in the young.
Diabetes care Jun, 2011 | Pubmed ID: 21562325
Rituximab selectively suppresses specific islet antibodies.
Diabetes Oct, 2011 | Pubmed ID: 21831969
Predicting the onset of Addison's disease: ACTH, renin, cortisol and 21-hydroxylase autoantibodies.
Clinical endocrinology May, 2012 | Pubmed ID: 22066755
Distinguishing persistent insulin autoantibodies with differential risk: nonradioactive bivalent proinsulin/insulin autoantibody assay.
Diabetes Jan, 2012 | Pubmed ID: 22124462
Proinsulin/Insulin autoantibodies measured with electrochemiluminescent assay are the earliest indicator of prediabetic islet autoimmunity.
Diabetes care Aug, 2013 | Pubmed ID: 23423694
GAD65 autoantibodies detected by electrochemiluminescence assay identify high risk for type 1 diabetes.
Diabetes Dec, 2013 | Pubmed ID: 23974918
Inhibition of increased circulating Tfh cell by anti-CD20 monoclonal antibody in patients with type 1 diabetes.
PloS one , 2013 | Pubmed ID: 24278195
Exploring T cell reactivity to gliadin in young children with newly diagnosed celiac disease.
Autoimmune diseases , 2014 | Pubmed ID: 24724018
Electrochemiluminescence assays for insulin and glutamic acid decarboxylase autoantibodies improve prediction of type 1 diabetes risk.
Diabetes technology & therapeutics Feb, 2015 | Pubmed ID: 25562486
Novel Association Between Immune-Mediated Susceptibility Loci and Persistent Autoantibody Positivity in Type 1 Diabetes.
Diabetes Aug, 2015 | Pubmed ID: 25829454
Regulatory vs. inflammatory cytokine T-cell responses to mutated insulin peptides in healthy and type 1 diabetic subjects.
Proceedings of the National Academy of Sciences of the United States of America Apr, 2015 | Pubmed ID: 25831495
Feasibility of screening for T1D and celiac disease in a pediatric clinic setting.
Pediatric diabetes Sep, 2016 | Pubmed ID: 26251221
Use of Dried Capillary Blood Sampling for Islet Autoantibody Screening in Relatives: A Feasibility Study.
Diabetes technology & therapeutics Dec, 2015 | Pubmed ID: 26375197
Islet Autoantibody Detection by Electrochemiluminescence (ECL) Assay.
Methods in molecular biology (Clifton, N.J.) , 2016 | Pubmed ID: 26659802
A multiplex assay combining insulin, GAD, IA-2 and transglutaminase autoantibodies to facilitate screening for pre-type 1 diabetes and celiac disease.
Journal of immunological methods Mar, 2016 | Pubmed ID: 26809048
Expression-Based Genome-Wide Association Study Links Vitamin D-Binding Protein With Autoantigenicity in Type 1 Diabetes.
Diabetes May, 2016 | Pubmed ID: 26983959
ECL-IAA and ECL-GADA Can Identify High-Risk Single Autoantibody-Positive Relatives in the TrialNet Pathway to Prevention Study.
Diabetes technology & therapeutics 07, 2016 | Pubmed ID: 26991969
Anti-Insulin Immune Responses Are Detectable in Dogs with Spontaneous Diabetes.
PloS one , 2016 | Pubmed ID: 27031512
CRISPR-Cas9-Mediated Modification of the NOD Mouse Genome With Ptpn22R619W Mutation Increases Autoimmune Diabetes.
Diabetes 08, 2016 | Pubmed ID: 27207523
The heterogeneity of islet autoantibodies and the progression of islet failure in type 1 diabetic patients.
Science China. Life sciences Sep, 2016 | Pubmed ID: 27225179
Predictors of slow progression to diabetes in children with multiple islet autoantibodies.
Journal of autoimmunity Aug, 2016 | Pubmed ID: 27255734
Celiac Disease Autoimmunity in Patients with Autoimmune Diabetes and Thyroid Disease among Chinese Population.
PloS one , 2016 | Pubmed ID: 27427767
Do Electrochemiluminescence Assays Improve Prediction of Time to Type 1 Diabetes in Autoantibody-Positive TrialNet Subjects?
Diabetes care 10, 2016 | Pubmed ID: 27456836
High-Throughput Screening in General Population for Type 1 Diabetes.
Diabetes technology & therapeutics 11, 2016 | Pubmed ID: 27860497
Islet-derived CD4 T-cells targeting proinsulin in human autoimmune diabetes.
Diabetes Dec, 2016 | Pubmed ID: 27920090
Higher Sensitivity and Earlier Identification of Celiac Disease Autoimmunity by a Nonradioactive Assay for Transglutaminase Autoantibodies.
Journal of immunology research , 2016 | Pubmed ID: 28127566
Identification of Unique Antigenic Determinants in the Amino Terminus of IA-2 (ICA512) in Childhood and Adult Autoimmune Diabetes: New Biomarker Development.
Diabetes care Apr, 2017 | Pubmed ID: 28174261
The Use of Electrochemiluminescence Assays to Predict Autoantibody and Glycemic Progression Toward Type 1 Diabetes in Individuals with Single Autoantibodies.
Diabetes technology & therapeutics Feb, 2017 | Pubmed ID: 28177779
T1D Autoantibodies: room for improvement?
Current opinion in endocrinology, diabetes, and obesity Aug, 2017 | Pubmed ID: 28509692
Dominant-negative loss of function arises from a second, more frequent variant within the SAND domain of autoimmune regulator (AIRE).
Journal of autoimmunity Mar, 2018 | Pubmed ID: 29129473
A subclass of serum anti-ZnT8 antibodies directed to the surface of live pancreatic β-cells.
The Journal of biological chemistry Jan, 2018 | Pubmed ID: 29184000
Altered homeostasis and development of regulatory T cell subsets represent an IL-2R-dependent risk for diabetes in NOD mice.
Science signaling Dec, 2017 | Pubmed ID: 29259102
Islet Autoantibody Detection by Electrochemiluminescence (ECL) Assay.
Journal of clinical & cellular immunology , 2017 | Pubmed ID: 29487479
Characteristics of slow progression to diabetes in multiple islet autoantibody-positive individuals from five longitudinal cohorts: the SNAIL study.
Diabetologia 06, 2018 | Pubmed ID: 29532109
Identical and Nonidentical Twins: Risk and Factors Involved in Development of Islet Autoimmunity and Type 1 Diabetes.
Diabetes care 02, 2019 | Pubmed ID: 30061316
PD-1 Inhibitor Immune-Related Adverse Events in Patients With Preexisting Endocrine Autoimmunity.
The Journal of clinical endocrinology and metabolism 10, 2018 | Pubmed ID: 30124874
Screening children for type 1 diabetes-associated antibodies at community health fairs.
Pediatric diabetes 11, 2019 | Pubmed ID: 31376227
High-throughput multiplexed autoantibody detection to screen type 1 diabetes and multiple autoimmune diseases simultaneously.
EBioMedicine Sep, 2019 | Pubmed ID: 31447394
Islet autoantibodies in disease prediction and pathogenesis.
Diabetology international Jan, 2020 | Pubmed ID: 31949998
Cost and Cost-Effectiveness of Large-Scale Screening for Type 1 Diabetes in Colorado.
Diabetes care Apr, 2020 | Pubmed ID: 32327420
The diabetic microenvironment causes mitochondrial oxidative stress in glomerular endothelial cells and pathological crosstalk with podocytes.
Cell communication and signaling : CCS 07, 2020 | Pubmed ID: 32641054
Persistent IL-2 Receptor Signaling by IL-2/CD25 Fusion Protein Controls Diabetes in NOD Mice by Multiple Mechanisms.
Diabetes 11, 2020 | Pubmed ID: 32843568
Large-Scale Screening in General Population Children for Celiac Disease with a Multiplex Electrochemiluminescence (ECL) Assay.
Journal of immunology research , 2020 | Pubmed ID: 33426098
Proinsulin-Reactive CD4 T Cells in the Islets of Type 1 Diabetes Organ Donors.
Frontiers in endocrinology , 2021 | Pubmed ID: 33841327
Autoimmune thyroid disease correlates to islet autoimmunity on zinc transporter 8 autoantibody.
Endocrine connections May, 2021 | Pubmed ID: 33909592
Novel autoantibodies to the β-cell surface epitopes of ZnT8 in patients progressing to type-1 diabetes.
Journal of autoimmunity 08, 2021 | Pubmed ID: 34130115
Improving clinical utility of GAD65 autoantibodies by electrochemiluminescence assay and clinical phenotype when identifying autoimmune adult-onset diabetes.
Diabetologia 09, 2021 | Pubmed ID: 34272582
High-affinity ZnT8 Autoantibodies by Electrochemiluminescence Assay Improve Risk Prediction for Type 1 Diabetes.
The Journal of clinical endocrinology and metabolism 11, 2021 | Pubmed ID: 34343303
Heterogeneity of DKA Incidence and Age-Specific Clinical Characteristics in Children Diagnosed With Type 1 Diabetes in the TEDDY Study.
Diabetes care 03, 2022 | Pubmed ID: 35043162
High-Throughput Multiplex Electrochemiluminescence Assay Applicable to General Population Screening for Type 1 Diabetes and Celiac Disease.
Diabetes technology & therapeutics Jul, 2022 | Pubmed ID: 35238620
1Barbara Davis Center for Diabetes, University of Colorado School of Medicine,
2Department of Endocrinology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences,
3Department of endocrinology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology
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