Mark Mamula, PhD
Professor of Medicine (Rheumatology)Cards
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Professor of Medicine (Rheumatology)
Biography
Dr. Mamula’s received degrees from UCLA, the University of Notre Dame and the University of Oklahoma. Dr. Mamula’s central research interests are in investigating the early events involved with breaking immune tolerance to self proteins, both in autoimmune disease and in tumor biology. Overall, it is the goal of Dr. Mamula's laboratory to understand the mechanisms that may shift this balance toward the initiation of anti-self immune responses. Seminal work from the Mamula lab elucidated the biochemical forms of autoantigens capable of breaking immunologic tolerance to intracellular autoantigens in systemic lupus erythematosus (SLE), and type 1 diabetes (T1D). Simply put, Dr. Mamula examines posttranslational protein modifications that alter cellular biology and immunity. These studies have now been applied to the development of novel therapeutic approaches in developing anti-tumor vaccines in breast cancer and colon cancer. In addition, studies from the Mamula laboratory first demonstrated the ability of B cells to present autoantigens in the triggering of T cell autoimmunity and in the phenomenon of epitope spreading in lupus autoimmunity. This work preceded more recent studies illustrating the how B cells transfer autoantigens to other antigen presenting cells, including dendritic cells and macrophages.
Appointments
Rheumatology
ProfessorPrimary
Other Departments & Organizations
Education & Training
- PhD
- University of Oklahoma (1986)
- MS
- University of Notre Dame (1982)
- BA
- University of California at Los Angeles (1979)
Research
Overview
Medical Research Interests
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Hester Doyle, PhD
Joseph Craft, MD
Insoo Kang, MD
Renelle Joseph-Gee, MS, BS
Richard Kibbey, MD/PhD
TuKiet Lam, PhD, BS
Autoantigens
Autoimmunity
T-Lymphocytes
Autoimmune Diseases
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 ResearchAltmetric
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 autoimmunity
2021
Gene expression signatures of target tissues in type 1 diabetes, lupus erythematosus, multiple sclerosis, and rheumatoid arthritis
Szymczak F, Colli M, Mamula M, Evans-Molina C, Eizirik D. Gene expression signatures of target tissues in type 1 diabetes, lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. Science Advances 2021, 7: eabd7600. PMID: 33523973, PMCID: PMC7787485, DOI: 10.1126/sciadv.abd7600.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsType 1 diabetesLupus erythematosusTarget tissuesRheumatoid arthritisMultiple sclerosisAutoimmune diseasesImmune systemSystemic lupus erythematosusTarget tissue levelRepurposing of drugsDisease-specific signaturesGene expression signaturesImmune assaultSimilar molecular signaturesClinical useTissue levelsDiseaseHigh expressionExpression signaturesDifferent diseasesErythematosusArthritisSclerosisDiabetesTherapy
2019
Islet Autoantibody Standardization Program 2018 Workshop: Interlaboratory Comparison of Glutamic Acid Decarboxylase Autoantibody Assay Performance
Lampasona V, Pittman D, Williams A, Achenbach P, Schlosser M, Akolkar B, Winter W, Laboratories P, Watson K, Weets I, Tao Y, Chen V, Yang Y, Uibo R, Reimand K, Knip M, Härkönen T, Chatenoud L, Achenbach P, Neidhoefer S, Schlosser M, Lampasona V, Kawasaki E, Batstra M, Cieremans T, Almås B, Opsion K, Wyka K, Castaño L, Ramelius A, Johansson I, Williams A, Furmaniak J, McDonald T, McLaughlin K, Christie M, Metz A, Mathew A, Hampe C, Lu C, Wasserfall C, Mann C, Pittman D, Ananta J, Yu L, Mamula M, Robinson P, Gaur V, Hagopian W. Islet Autoantibody Standardization Program 2018 Workshop: Interlaboratory Comparison of Glutamic Acid Decarboxylase Autoantibody Assay Performance. Clinical Chemistry 2019, 65: 1141-1152. PMID: 31409598, PMCID: PMC8936135, DOI: 10.1373/clinchem.2019.304196.Peer-Reviewed Original ResearchCitationsAltmetric
2018
AI-13 Therapeutic inhibitors of antigen presentation pathways in SLE
Raycroft M, Gee R, Merkel J, Mamula M. AI-13 Therapeutic inhibitors of antigen presentation pathways in SLE. 2018, a6.2-a6. DOI: 10.1136/lupus-2018-lsm.13.Peer-Reviewed Original Research
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 & 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
Posttranslational modification of islet autoantigens in type 1 diabetes
Yang M, Wen L, Herold K, Mamula M. Posttranslational modification of islet autoantigens in type 1 diabetes. The Journal Of Immunology 2016, 196: 118.9-118.9. DOI: 10.4049/jimmunol.196.supp.118.9.Peer-Reviewed Original ResearchCitationsConceptsAnti-insulin autoimmunityType 1 diabetesNon-obese diabetic (NOD) micePrediabetic NOD miceDevelopment of T1D.Onset of hyperglycemiaHuman pancreatic isletsNOD miceHuman T1DHuman T1D.Islet autoantigensImmune toleranceAutoimmune responseDiabetic miceAutoimmune diseasesInflammatory cytokinesTissue pathologyPancreatic isletsAutoantibodiesT1D.Islet proteinsAutoantigensOxidative stressInsulin biosynthesisAutoimmunity
2014
Targeting multiple ErbB family members by EGFR peptide immunization. (VAC12P.1016)
Doyle H, Koski R, Bonafé N, Bruck R, Tagliatela S, Gee R, Mamula M. Targeting multiple ErbB family members by EGFR peptide immunization. (VAC12P.1016). The Journal Of Immunology 2014, 192: 206.5-206.5. DOI: 10.4049/jimmunol.192.supp.206.5.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorMonoclonal antibody treatmentAntibody treatmentAnti-EGFR monoclonal antibodiesMonoclonal antibodiesPeptide-based vaccinationAnti-tumor antibodiesMultiple EGFR family membersNatural anti-tumor antibodiesMembrane-proximal epitopeErbB family membersFamily membersGrowth factor receptorStandard chemotherapyTumor vaccinesEGFR family membersCurrent treatmentDrug infusionTumor antigensGreater tumorSerum inhibitsSide effectsTumor killingSingle agentSolid tumorsIsoaspartyl modification of ZAP70 signaling molecule alters T cell responses (555.9)
Yang M, Clarke S, Mamula M. Isoaspartyl modification of ZAP70 signaling molecule alters T cell responses (555.9). The FASEB Journal 2014, 28 DOI: 10.1096/fasebj.28.1_supplement.555.9.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusT cell responsesCell responsesT cell immune responsesCell immune responsesAutoreactive immune cellsT cell defectsMajor target organT-cell immunodeficiencyT cell hyperproliferationPIMT-deficient miceProtein L-isoaspartyl methyltransferaseLupus pathologyAutoimmune miceLupus erythematosusImmune toleranceImmune cellsDeficient miceCell immunodeficiencyImmune responseTarget organsT cell signalingImmune systemAutoimmune BCell hyperproliferation
Clinical Trials
Current Trials
Yale Rheumatology Program Patient Registry and Bio-Repository
HIC ID2000026608REGRoleSub InvestigatorPrimary Completion Date06/01/2030Recruiting ParticipantsGenderBothAge18 years - 99 years
News
News
- October 21, 2024
Dr. Mark Mamula on Yale Cancer Answers: Breaking Boundaries: The Science of Immune Tolerance
- June 26, 2024
Got a Game? Boost Your Performance
- March 05, 2024Source: Yale News
Novel Cancer Vaccine Offers New Hope for Dogs — and Those Who Love Them
- October 02, 2023Source: Hartford Courant
CT Researcher Creates Immunotherapy for Canine Cancer. It Helps Man’s Best Friend Live Longer.