Mei-Ling Yang, PhD
Assistant Professor AdjunctCards
Contact Info
About
Titles
Assistant Professor Adjunct
Biography
Dr. Mei-Ling Yang is Associate Research Scientist for Rheumatology, Allergy & Immunology at Yale University School of Medicine. She obtained her PhD degree in Biochemistry and Molecular Biology at National Taiwan University at 2002 and then joined the laboratory of Dr. Mark Mamula for her postdoctoral training. She studied the role of protein modifications in lupus autoimmunity under Arthritis Foundation Postdoctoral Fellowship. Dr. Yang became part of the faculty in 2008 and current research focus is to understand how inflammation and posttranslational modifications evoke autoimmune responses in type 1 diabetes and systemic lupus erythematosus.
Appointments
Rheumatology
Assistant Professor AdjunctPrimary
Other Departments & Organizations
- Internal Medicine
- Rheumatology
- Rheumatology, Allergy, & Immunology
Education & Training
- PhD
- National Taiwan Univ (2002)
- BS
- National Taiwan Univ (1993)
Research
Overview
Post-translational protein modification influences immunologic responses ranging from intracellular signaling to protein processing and presentation and creates neo-epitopes from self-proteins to break immune tolerance that leads to autoimmune diseases. Systemic erythematosus lupus (SLE) and type 1 diabetes (T1D) are the complex autoimmune diseases involving multiple genetic and environmental factors. My research is to investigate the role of posttranslational protein modifications including isoaspartyl modification, methylation, carbonylation and citrullination on genetic association analysis and biological functions of T cells in the pathogenesis of SLE and T1D. My work provides new insight into the diagnosis of autoimmune diseases where the specific auto-antigen is unknown and provides targets in autoimmune pathways to discover novel therapeutic concepts and biomarkers for inflammatory conditions.
Medical Research Interests
ORCID
0000-0003-1687-2463
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Mark Mamula, PhD
Renelle Joseph-Gee, MS, BS
TuKiet Lam, PhD, BS
Hester Doyle, PhD
Ana Luisa Perdigoto, MD, PhD
Insoo Kang, MD
Diabetes Mellitus, Type 1
Autoimmune Diseases
Lupus Erythematosus, Systemic
Publications
2023
Natural isoaspartyl protein modification of ZAP70 alters T cell responses in lupus
Yang M, Lam T, Kanyo J, Kang I, Zhou Z, Clarke S, Mamula M. Natural isoaspartyl protein modification of ZAP70 alters T cell responses in lupus. Autoimmunity 2023, 56: 2282945. PMID: 37994408, PMCID: PMC10897934, DOI: 10.1080/08916934.2023.2282945.Peer-Reviewed Original ResearchCitationsAltmetric
2022
A discovery-based proteomics approach identifies protein disulphide isomerase (PDIA1) as a biomarker of β cell stress in type 1 diabetes
Syed F, Singhal D, Raedschelders K, Krishnan P, Bone R, McLaughlin M, Van Eyk J, Mirmira R, Yang M, Mamula M, Wu H, Liu X, Evans-Molina C. A discovery-based proteomics approach identifies protein disulphide isomerase (PDIA1) as a biomarker of β cell stress in type 1 diabetes. EBioMedicine 2022, 87: 104379. PMID: 36463755, PMCID: PMC9719098, DOI: 10.1016/j.ebiom.2022.104379.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsT-cell adoptive transferCell adoptive transferNOD miceNOD-SCID miceType 1 diabetesΒ-cell stressAdoptive transferPre-diabetic NOD miceFemale NOD miceNon-diabetic controlsRecent-onset T1DSerum of childrenDistinct mouse modelsΒ-cell functionHuman organ donorsWeeks of agePotential human biomarkersDisease-related changesΒ-cell deathCell protein expressionNOD isletsAutoantibody positivityDiabetes onsetT1D developmentImmune activationBiomarkers of autoimmunity and beta cell metabolism in type 1 diabetes
Yang M, Kibbey R, Mamula M. Biomarkers of autoimmunity and beta cell metabolism in type 1 diabetes. Frontiers In Immunology 2022, 13: 1028130. PMID: 36389721, PMCID: PMC9647083, DOI: 10.3389/fimmu.2022.1028130.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPosttranslational protein modificationMetabolic pathwaysType 1 diabetesCellular metabolic pathwaysImportant biological functionsAutoimmune diseasesBeta cellsCellular metabolic dysfunctionPancreatic isletsProtein modificationBiological functionsProtein structureInsulin-producing beta cellsBiomarkers of autoimmunityChronic autoimmune diseaseCell metabolismBeta-cell metabolismNumerous autoimmune diseasesPancreatic beta cellsPotential pathological consequencesNormal metabolic pathwaysDisease activityPathological consequencesSpecific autoantigensSpecific autoimmunityImmune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes
Perdigoto AL, Deng S, Du KC, Kuchroo M, Burkhardt DB, Tong A, Israel G, Robert ME, Weisberg SP, Kirkiles-Smith N, Stamatouli AM, Kluger HM, Quandt Z, Young A, Yang ML, Mamula MJ, Pober JS, Anderson MS, Krishnaswamy S, Herold KC. Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes. JCI Insight 2022, 7: e156330. PMID: 35925682, PMCID: PMC9536276, DOI: 10.1172/jci.insight.156330.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCheckpoint inhibitorsΒ-cellsPD-1/PD-L1 pathwayT-lymphocyte antigen-4PD-1 blockadePD-L1 pathwayDeath ligand 1NOD mouse modelDevelopment of diabetesHuman β-cellsAutoimmune complicationsNOD miceΒ-cell populationDeath-1Diabetes mellitusImmune infiltratesInflammatory mediatorsPancreatic inflammationPD-L1Induced diabetesLymphocytic infiltrationInflammatory cytokinesAntigen-4Immune cellsT cellsCarbonyl Posttranslational Modification Associated With Early-Onset Type 1 Diabetes Autoimmunity.
Yang ML, Connolly SE, Gee RJ, Lam TT, Kanyo J, Peng J, Guyer P, Syed F, Tse HM, Clarke SG, Clarke CF, James EA, Speake C, Evans-Molina C, Arvan P, Herold KC, Wen L, Mamula MJ. Carbonyl Posttranslational Modification Associated With Early-Onset Type 1 Diabetes Autoimmunity. Diabetes 2022, 71: 1979-1993. PMID: 35730902, PMCID: PMC9450849, DOI: 10.2337/db21-0989.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsType 1 diabetesNOD miceMurine type 1 diabetesHuman type 1 diabetesDecreased glucose-stimulated insulin secretionAnti-insulin autoimmunityPrediabetic NOD miceGlucose-stimulated insulin secretionOnset Type 1T cell responsesOnset of hyperglycemiaCirculation of patientsAutoreactive CD4Insulin ratioInsulin secretionDiabetesPancreatic isletsType 1Islet proteinsOxidative stressAutoimmunitySelect groupMiceCarbonyl modificationOnsetCitrullination of glucokinase is linked to autoimmune diabetes
Yang ML, Horstman S, Gee R, Guyer P, Lam TT, Kanyo J, Perdigoto AL, Speake C, Greenbaum CJ, Callebaut A, Overbergh L, Kibbey RG, Herold KC, James EA, Mamula MJ. Citrullination of glucokinase is linked to autoimmune diabetes. Nature Communications 2022, 13: 1870. PMID: 35388005, PMCID: PMC8986778, DOI: 10.1038/s41467-022-29512-0.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsGlucose-stimulated insulin secretionResult of inflammationType 1 diabetesBeta-cell metabolismPancreatic beta cellsAutoimmune diabetesNOD miceAutoreactive CD4Inflammatory cytokinesAutoimmune biomarkersInsulin secretionT cellsBeta cellsType 1InflammationBiologic activityReactive oxygen speciesDiabetesPost-translational modificationsDiabetes biomarkersGlycogen synthesisBiomarkersCitrullinationGlucokinaseOxygen species
2021
Citrullination and PAD Enzyme Biology in Type 1 Diabetes – Regulators of Inflammation, Autoimmunity, and Pathology
Yang ML, Sodré FMC, Mamula MJ, Overbergh L. Citrullination and PAD Enzyme Biology in Type 1 Diabetes – Regulators of Inflammation, Autoimmunity, and Pathology. Frontiers In Immunology 2021, 12: 678953. PMID: 34140951, PMCID: PMC8204103, DOI: 10.3389/fimmu.2021.678953.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsRheumatoid arthritisPeptidylarginine deiminaseAutoimmune diseasesNeutrophil extracellular trap formationSystemic lupus erythematosusRole of neutrophilsPathogenesis of T1D.Different autoimmune diseasesType 1 diabetesExtracellular trap formationNovel therapeutic strategiesGenetic susceptibility factorsAmino acid citrullinePAD inhibitionNOD miceLupus erythematosusT1D patientsAutoimmune responseAutoreactive responsesDiabetes developmentMultiple sclerosisPathogenic roleInflammatory stressT cellsNeutrophil biology
2018
Inflammation-Induced Citrullinated Glucose-Regulated Protein 78 Elicits Immune Responses in Human Type 1 Diabetes
Buitinga M, Callebaut A, Sodré F, Crèvecoeur I, Blahnik-Fagan G, Yang ML, Bugliani M, Arribas-Layton D, Marré M, Cook DP, Waelkens E, Mallone R, Piganelli JD, Marchetti P, Mamula MJ, Derua R, James EA, Mathieu C, Overbergh L. Inflammation-Induced Citrullinated Glucose-Regulated Protein 78 Elicits Immune Responses in Human Type 1 Diabetes. Diabetes 2018, 67: 2337-2348. PMID: 30348823, PMCID: PMC6973547, DOI: 10.2337/db18-0295.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsType 1 diabetesHuman type 1 diabetesΒ-cellsEffector memory cellsCentral memory cellsT cell responsesHealthy control subjectsTumor necrosis factorUse of HLAElicit immune responsesHuman type 1Glucose-regulated protein 78Generation of neoantigensGeneration of neoepitopesΒ-cell proteinsAutoantibody titersImmune toleranceNovel autoantigenControl subjectsInterleukin-1βInflammatory stressNecrosis factorImmune responseDiabetesELISA technique
2017
Oxidative Modifications in Tissue Pathology and Autoimmune Disease
Yang ML, Doyle H, Clarke SG, Herold K, Mamula M. Oxidative Modifications in Tissue Pathology and Autoimmune Disease. Antioxidants And Redox Signaling 2017, 29: 1415-1431. PMID: 29088923, PMCID: PMC6166690, DOI: 10.1089/ars.2017.7382.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPost-translational protein modificationReactive oxygen speciesProtein modificationGene expressionAberrant gene expressionInitiation of apoptosisChromosome inactivationOxidative stressDNA methylationCellular pathwaysGenetic elementsLevels of tissueMicroenvironmental influencesProtein expressionOxygen speciesOxidative modificationTissue pathogenesisPathwayExpressionTherapeutic manipulationPotential therapeutic manipulationEnvironmental influencesCellsIntracellular autoantigensSilencing
2016
The role for neutrophil extracellular traps in cystic fibrosis autoimmunity
Skopelja S, Hamilton BJ, Jones JD, Yang ML, Mamula M, Ashare A, Gifford AH, Rigby WF. The role for neutrophil extracellular traps in cystic fibrosis autoimmunity. JCI Insight 2016, 1: e88912. PMID: 27777975, PMCID: PMC5070963, DOI: 10.1172/jci.insight.88912.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsAnti-citrullinated protein autoantibodiesNeutrophil extracellular trapsAnti-BPI autoantibodiesDevelopment of autoimmunityCystic fibrosisBactericidal permeability-increasing proteinProtein autoantibodiesExtracellular trapsACPA-positive RA patientsDiminished lung functionRheumatoid arthritis patientsAirway inflammationAutoantibody levelsCF disease severityRA patientsRespiratory failureArthritis patientsLung functionSputum cultureAutoantibody profileLung damagePermeability-increasing proteinAutoantibody specificitiesChronic infectionCF patients