Mark Mamula, PhD
Research & Publications
Biography
News
Research Summary
The immune system maintains a delicate balance in its ability to recognize and eliminate foreign pathogens versus its ability to be tolerant of self tissues. Dr. Mamula has had a long standing interest in investigating the early events involved with the induction of autoimmunity. It is the goal of Dr. Mamula's laboratory to understand the mechanisms that may shift this balance toward the initiation of autoimmune responses. In particular, his efforts have centered on the molecular interactions of autoimmune B and T lymphocyte responses to intracellular autoantigens in systemic lupus erythematosus (SLE). His laboratory is also interested in determining the forms of autoantigens capable of breaking immunologic tolerance, the processing of these autoantigens, and understanding the role of autoreactive T cells in autoimmune diseases such as lupus and diabetes. More recently, Dr. Mamula has also been applying some his studies towards developing “autoimmune” responses against tumor tissues, in particular, models of melanoma and breast cancer. These latter studies have evolved into novel approaches for the design of therapeutic tumor vaccines.
Specialized Terms: Autoimmune diseases
Extensive Research Description
Coauthors
Research Interests
Autoantigens; Autoimmune Diseases; Immune System; Rheumatology; T-Lymphocytes; Autoimmunity
Selected Publications
- A discovery-based proteomics approach identifies protein disulphide isomerase (PDIA1) as a biomarker of β cell stress in type 1 diabetesSyed 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.
- Biomarkers of autoimmunity and beta cell metabolism in type 1 diabetesYang M, Kibbey R, Mamula M. Biomarkers of autoimmunity and beta cell metabolism in type 1 diabetes. Frontiers In Immunology 2022, 13: 1028130. PMCID: PMC9647083, DOI: 10.3389/fimmu.2022.1028130.
- Biomarkers of autoimmunity and beta cell metabolism in type 1 diabetesYang 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.
- Regulation of metabolism by protein modifications in autoimmunityYang M, James E, Overbergh L, Herold K, Mamula M. Regulation of metabolism by protein modifications in autoimmunity. The Journal Of Immunology 2022, 208: 108.09-108.09. DOI: 10.4049/jimmunol.208.supp.108.09.
- Gene expression signatures of target tissues in type 1 diabetes, lupus erythematosus, multiple sclerosis, and rheumatoid arthritisSzymczak 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.
- Islet Autoantibody Standardization Program 2018 Workshop: Interlaboratory Comparison of Glutamic Acid Decarboxylase Autoantibody Assay PerformanceLampasona V, Pittman D, Williams A, Achenbach P, Schlosser M, Akolkar B, Winter W, 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.
- AI-13 Therapeutic inhibitors of antigen presentation pathways in SLERaycroft 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.
- Oxidative Modifications in Tissue Pathology and Autoimmune DiseaseYang 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.
- Posttranslational modification of islet autoantigens in type 1 diabetesYang 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.
- 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.
- Isoaspartyl 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.
- Therapeutic inhibition of gut antigen trafficking through scavenger receptor A (P5027)Raycroft M, Mamula M. Therapeutic inhibition of gut antigen trafficking through scavenger receptor A (P5027). The Journal Of Immunology 2013, 190: 110.14-110.14. DOI: 10.4049/jimmunol.190.supp.110.14.
- Identification of posttranslational modified autoantigens in Type 1 diabetes. (P4152)Yang M, Connolly S, Wen L, Herold K, Mamula M. Identification of posttranslational modified autoantigens in Type 1 diabetes. (P4152). The Journal Of Immunology 2013, 190: 172.3-172.3. DOI: 10.4049/jimmunol.190.supp.172.3.
- S-Adenosylmethionine-dependent methylation modulates T cell immune response and lupus autoimmunity (116.13)Yang M, Gee A, Gee R, Mamula M. S-Adenosylmethionine-dependent methylation modulates T cell immune response and lupus autoimmunity (116.13). The Journal Of Immunology 2012, 188: 116.13-116.13. DOI: 10.4049/jimmunol.188.supp.116.13.
- Chapter 8 B-Lymphocyte Biology in SLEMamula M. Chapter 8 B-Lymphocyte Biology in SLE. 2011, 143-161. DOI: 10.1016/b978-0-12-374994-9.10008-7.
- Sequential autoantigenic determinants of the small nuclear ribonucleoprotein Sm D shared by human lupus autoantibodies and MRL Ipr/lpr antibodiesJAMES J, MAMULA M, HARLEY J. Sequential autoantigenic determinants of the small nuclear ribonucleoprotein Sm D shared by human lupus autoantibodies and MRL Ipr/lpr antibodies. Clinical & Experimental Immunology 2008, 98: 419-426. PMID: 7527740, PMCID: PMC1534503, DOI: 10.1111/j.1365-2249.1994.tb05507.x.
- Scavenger receptor type AI mediates antigen transfer from human B cells to other APCsHarvey B, Quan T, Roman R, Rudenga B, Craft J, Mamula M. Scavenger receptor type AI mediates antigen transfer from human B cells to other APCs. The FASEB Journal 2008, 22: 1068.14-1068.14. DOI: 10.1096/fasebj.22.1_supplement.1068.14.
- Isoaspartyl Posttranslational Modification In Drug‐Induced LupusYang M, Mamula M. Isoaspartyl Posttranslational Modification In Drug‐Induced Lupus. The FASEB Journal 2008, 22: 668.20-668.20. DOI: 10.1096/fasebj.22.1_supplement.668.20.
- Intracellular protein modification associated with altered T cell functions in autoimmunityYang M, Doyle H, Gee R, Lowenson J, Clarke S, Lawson B, Aswad D, Mamula M. Intracellular protein modification associated with altered T cell functions in autoimmunity. The Journal Of Immunology 2006, 177: 8878-8878. DOI: 10.4049/jimmunol.177.12.8878.
- Increase in intracellular protein modification associated with altered lymphocyte functions in autoimmunityYang M, Doyle H, Gee R, Aswad D, Mamula M. Increase in intracellular protein modification associated with altered lymphocyte functions in autoimmunity. The FASEB Journal 2006, 20: a964-a964. DOI: 10.1096/fasebj.20.5.a964-a.
- From T to B and back again: positive feedback in systemic autoimmune diseaseShlomchik M, Craft J, Mamula M. From T to B and back again: positive feedback in systemic autoimmune disease. Nature Reviews Immunology 2001, 1: 147-153. PMID: 11905822, DOI: 10.1038/35100573.
- Post-translational protein modifications in antigen recognition and autoimmunityDoyle H, Mamula M. Post-translational protein modifications in antigen recognition and autoimmunity. Trends In Immunology 2001, 22: 443-449. PMID: 11473834, DOI: 10.1016/s1471-4906(01)01976-7.
- Structural Integrity of Histone H2B in Vivo Requires the Activity of Protein l-IsoaspartateO-Methyltransferase, a Putative Protein Repair Enzyme*Young A, Carter W, Doyle H, Mamula M, Aswad D. Structural Integrity of Histone H2B in Vivo Requires the Activity of Protein l-IsoaspartateO-Methyltransferase, a Putative Protein Repair Enzyme*. Journal Of Biological Chemistry 2001, 276: 37161-37165. PMID: 11479322, DOI: 10.1074/jbc.m106682200.
- Lupus autoantigens: Their origins, forms, and presentationDoyle H, Yan J, Liang B, Mamula M. Lupus autoantigens: Their origins, forms, and presentation. Immunologic Research 2001, 24: 131-147. PMID: 11594452, DOI: 10.1385/ir:24:2:131.
- Autoantibody Responses and Pathology Regulated by B7-1 and B7-2 Costimulation in MRL/lpr LupusLiang B, Kashgarian M, Sharpe A, Mamula M. Autoantibody Responses and Pathology Regulated by B7-1 and B7-2 Costimulation in MRL/lpr Lupus. The Journal Of Immunology 2000, 165: 3436-3443. PMID: 10975864, DOI: 10.4049/jimmunol.165.6.3436.
- Molecular mimicry and the role of B lymphocytes in the processing of autoantigensLiang B, Mamula* M. Molecular mimicry and the role of B lymphocytes in the processing of autoantigens. Cellular And Molecular Life Sciences 2000, 57: 561-568. PMID: 11130456, DOI: 10.1007/pl00000718.
- Isoaspartyl Post-translational Modification Triggers Autoimmune Responses to Self-proteins*Mamula M, Gee R, Elliott J, Sette A, Southwood S, Jones P, Blier P. Isoaspartyl Post-translational Modification Triggers Autoimmune Responses to Self-proteins*. Journal Of Biological Chemistry 1999, 274: 22321-22327. PMID: 10428801, DOI: 10.1074/jbc.274.32.22321.
- T Cell Autoimmunity in LupusMamula M. T Cell Autoimmunity in Lupus. 1999, 202-219. DOI: 10.1007/978-1-59259-703-1_13.
- Advances in autoantibodies in SLEvon Mühlen C, Chan E, Anglés-Cano E, Mamula M, Garcia-De La Torre I, Fritzler M. Advances in autoantibodies in SLE. Lupus 1998, 7: 507-514. PMID: 9863891, DOI: 10.1191/096120398678920613.
- Epitope spreading: the role of self peptides and autoantigen processing by B lymphocytesMamula M, Mamula M. Epitope spreading: the role of self peptides and autoantigen processing by B lymphocytes. Immunological Reviews 1998, 164: 231-233. PMID: 9795779, DOI: 10.1111/j.1600-065x.1998.tb01223.x.
- Autoreactive B Cell Regulation: Peripheral Induction of Developmental Arrest by Lupus-Associated AutoantigensSantulli-Marotto S, Retter M, Gee R, Mamula M, Clarke S. Autoreactive B Cell Regulation: Peripheral Induction of Developmental Arrest by Lupus-Associated Autoantigens. Immunity 1998, 8: 209-219. PMID: 9492002, DOI: 10.1016/s1074-7613(00)80473-2.
- Trafficking of Adoptively Transferred B Lymphocytes in B-Lymphocyte-Deficient MiceRoth R, Mamula M. Trafficking of Adoptively Transferred B Lymphocytes in B-Lymphocyte-Deficient Mice. Journal Of Experimental Biology 1997, 200: 2057-2062. PMID: 9246787, DOI: 10.1242/jeb.200.14.2057.
- B Lymphocytes as Autoantigen‐presenting Cells in the Amplification of AutoimmunityaROTH R, GEE R, MAMULA M. B Lymphocytes as Autoantigen‐presenting Cells in the Amplification of Autoimmunitya. Annals Of The New York Academy Of Sciences 1997, 815: 88-100. PMID: 9186642, DOI: 10.1111/j.1749-6632.1997.tb52047.x.
- B7 costimulation and autoantigen specificity enable B cells to activate autoreactive T cells.Roth R, Nakamura T, Mamula M. B7 costimulation and autoantigen specificity enable B cells to activate autoreactive T cells. The Journal Of Immunology 1996, 157: 2924-31. PMID: 8816398, DOI: 10.4049/jimmunol.157.7.2924.
- Lupus Autoimmunity; From Peptides to ParticlesMAMULA M. Lupus Autoimmunity; From Peptides to Particles. Immunological Reviews 1995, 144: 301-314. PMID: 7590818, DOI: 10.1111/j.1600-065x.1995.tb00074.x.
- The expression of self antigenic determinants: implications for tolerance and autoimmunityMamula M, Craft J. The expression of self antigenic determinants: implications for tolerance and autoimmunity. Current Opinion In Immunology 1994, 6: 882-886. PMID: 7536009, DOI: 10.1016/0952-7915(94)90008-6.
- Do B cells drive the diversification of immune responses?Mamula M, Janeway C. Do B cells drive the diversification of immune responses? Trends In Immunology 1993, 14: 151-152. PMID: 8098941, DOI: 10.1016/0167-5699(93)90274-o.
- The inability to process a self-peptide allows autoreactive T cells to escape tolerance.Mamula M. The inability to process a self-peptide allows autoreactive T cells to escape tolerance. Journal Of Experimental Medicine 1993, 177: 567-571. PMID: 8381158, PMCID: PMC2190887, DOI: 10.1084/jem.177.2.567.
- Rules for Peptide Presentation by MHC Class II MoleculesJaneway C, Mamula M, Rudensky A. Rules for Peptide Presentation by MHC Class II Molecules. International Reviews Of Immunology 1993, 10: 301-311. PMID: 8294843, DOI: 10.3109/08830189309061705.
- Breaking T cell tolerance with foreign and self co-immunogens. A study of autoimmune B and T cell epitopes of cytochrome c.Mamula M, Lin R, Janeway C, Hardin J. Breaking T cell tolerance with foreign and self co-immunogens. A study of autoimmune B and T cell epitopes of cytochrome c. The Journal Of Immunology 1992, 149: 789-95. PMID: 1321851, DOI: 10.4049/jimmunol.149.3.789.
- Anti-Ro autoantibody with cross-reactive binding to the heavy chain of immunoglobulin G.Mamula M, Harley J. Anti-Ro autoantibody with cross-reactive binding to the heavy chain of immunoglobulin G. The Yale Journal Of Biology And Medicine 1992, 65: 277-87. PMID: 1290272, PMCID: PMC2589586.
- Induction of autoreactive B cells allows priming of autoreactive T cells.Lin R, Mamula M, Hardin J, Janeway C. Induction of autoreactive B cells allows priming of autoreactive T cells. Journal Of Experimental Medicine 1991, 173: 1433-1439. PMID: 1851798, PMCID: PMC2190847, DOI: 10.1084/jem.173.6.1433.
- Importance of the immune response to the Ro/La particle in the development of congenital heart block and neonatal lupus erythematosus.Silverman E, Mamula M, Hardin J, Laxer R. Importance of the immune response to the Ro/La particle in the development of congenital heart block and neonatal lupus erythematosus. The Journal Of Rheumatology 1991, 18: 120-4. PMID: 2023181.
- The specificity of human anti-cytochrome c autoantibodies that arise in autoimmune disease.Mamula M, Jemmerson R, Hardin J. The specificity of human anti-cytochrome c autoantibodies that arise in autoimmune disease. The Journal Of Immunology 1990, 144: 1835-40. PMID: 1689756, DOI: 10.4049/jimmunol.144.5.1835.
- Human monoclonal anti-La antibodies. The La protein resides on a subset of Ro particles.Mamula M, Silverman E, Laxer R, Bentur L, Isacovics B, Hardin J. Human monoclonal anti-La antibodies. The La protein resides on a subset of Ro particles. The Journal Of Immunology 1989, 143: 2923-8. PMID: 2478628, DOI: 10.4049/jimmunol.143.9.2923.
- The Ro ribonucleoprotein particle: Induction of autoantibodies and the detection of Ro RNAs among speciesMamula M, O'Brien C, Harley J, Hardin J. The Ro ribonucleoprotein particle: Induction of autoantibodies and the detection of Ro RNAs among species. Clinical Immunology 1989, 52: 435-446. PMID: 2503280, DOI: 10.1016/0090-1229(89)90158-x.
- The Year in Immunology 1988. Cellular, Molecular and Clinical AspectsMamula M. The Year in Immunology 1988. Cellular, Molecular and Clinical Aspects. The Yale Journal Of Biology And Medicine 1989, 62: 412-413. PMCID: PMC2589075.
- Human Immunogenetics. Basic Principles and Clinical RelevanceMamula M. Human Immunogenetics. Basic Principles and Clinical Relevance. The Yale Journal Of Biology And Medicine 1989, 62: 335-335. PMCID: PMC2589122.
- Implications of anti-Ro/Sjögren's syndrome A antigen autoantibody in normal sera for autoimmunity.Gaither K, Fox O, Yamagata H, Mamula M, Reichlin M, Harley J. Implications of anti-Ro/Sjögren's syndrome A antigen autoantibody in normal sera for autoimmunity. Journal Of Clinical Investigation 1987, 79: 841-846. PMID: 3546381, PMCID: PMC424215, DOI: 10.1172/jci112892.
- The Ro/SSA autoantigen as an immunogen. Some anti-Ro/SSA antibody binds IgG.Mamula M, Fox O, Yamagata H, Harley J. The Ro/SSA autoantigen as an immunogen. Some anti-Ro/SSA antibody binds IgG. Journal Of Experimental Medicine 1986, 164: 1889-1901. PMID: 3097237, PMCID: PMC2188496, DOI: 10.1084/jem.164.6.1889.
- Role of macrophage lipids in regulating tumoricidal activitySchlager S, Madden L, Meltzer M, Bara S, Mamula M. Role of macrophage lipids in regulating tumoricidal activity. Cellular Immunology 1983, 77: 52-68. PMID: 6301697, DOI: 10.1016/0008-8749(83)90006-0.
- Mamula, M.J. 2010. B lymphocyte biology in SLE. In: Systemic Lupus Erythematosus, 5th Edition, Elsevier Publications. Edited by R.G. Lahita, T. Koike, J. Buyon, and G. Tsokos.Mamula, M.J. 2010. B lymphocyte biology in SLE. In: Systemic Lupus Erythematosus, 5th Edition, Elsevier Publications. Edited by R.G. Lahita, T. Koike, J. Buyon, and G. Tsokos.
Clinical Trials
Conditions | Study Title |
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Arthritis | Yale Rheumatology Program Patient Registry and Bio-Repository |