Autoantigens; Autoimmune Diseases; Immune System; Rheumatology; T-Lymphocytes; Autoimmunity
Skin Diseases Research Center, Yale
WHRY Pilot Project Program Investigators
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
Dr. Mamula is studying how, in lupus, the body targets itself for attack by its own immune system. Identifying the mechanisms that initiate this process can then help in devising an intervention that will stop this self-destructive cascade.
Inhibition of antigen trafficking through scavenger receptor A.
Raycroft, M.T., M. Bruck, and M.J. Mamula. 2011. Manipulation of antigen processing by inhibitors of scavenger receptor A. J. Biol. Chem. 287:5310-16. PMID: 22215667.
- 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.
Editing antigen processing: Antigen transfer between human B lymphocytes and macrophages mediated by class A scavenger receptors.
Harvey, B.P., T. Quan, B. Rudenga, R. Roman, J. Craft, and M.J. Mamula. 2008. Editing antigen processing: Antigen transfer between human B lymphocytes and macrophages mediated by class A scavenger receptors. J. Immunol. 181:4043-4051.
ntigen presentation and transfer between B cells and macrophages.
Harvey, B.P., R.J. Gee, A.M. Haberman, M.J. Shlomchik, and M.J. Mamula. 2007. Antigen presentation and transfer between B cells and macrophages. Eur. J. Immunol. 37:1739-1751.
Altered immunogenicity of isoaspartate-containing proteins.
Doyle, H.A., R.J. Gee, and M.J. Mamula. 2007. Altered immunogenicity of isoaspartate-containing proteins. Autoimmunity 40:131-137.
Isoaspartyl posttranslational modification triggers anti-tumor T and B lymphocyte immunity.
Doyle, H.A., J. Zhou, M.J. Wolff, R.M. Roman, R.J. Gee, R.A. Koski, and M.J. Mamula. 2006. Isoaspartyl posttranslational modification triggers anti-tumor T and B lymphocyte immunity. J. Biol. Chem. 281:32676-32683.
Intracellular protein modification associated with altered T cell functions in autoimmunity.
Yang, M-L., H.A. Doyle, R.J. Gee, J.D. Lowenson, S.A. Clarke, B.R. Lawson, D.W. Aswad, and M.J. Mamula. 2006. Intracellular protein modification associated with altered T cell functions in autoimmunity. J. Immunol., 177:4541-4549.
Full List of PubMed Publications
- Yang ML, Doyle HA, Clarke SG, Herold KC, Mamula MJ: Oxidative Modifications in Tissue Pathology and Autoimmune Disease. Antioxid Redox Signal. 2017 Dec 11; 2017 Dec 11. PMID: 29088923
- Vudattu NK, Waldron-Lynch F, Truman LA, Deng S, Preston-Hurlburt P, Torres R, Raycroft MT, Mamula MJ, Herold KC: Humanized mice as a model for aberrant responses in human T cell immunotherapy. J Immunol. 2014 Jul 15; 2014 Jun 18. PMID: 24943216
- Doyle HA, Yang ML, Raycroft MT, Gee RJ, Mamula MJ: Autoantigens: novel forms and presentation to the immune system. Autoimmunity. 2014 Jun; 2013 Nov 5. PMID: 24191689
- Harvey BP, Raycroft MT, Quan TE, Rudenga BJ, Roman RM, Craft J, Mamula MJ: Transfer of antigen from human B cells to dendritic cells. Mol Immunol. 2014 Mar; 2013 Dec 3. PMID: 24309484
- Mamula MJ: Editorial: B cells: not just making immunoglobulin anymore. Arthritis Rheumatol. 2014 Jan. PMID: 24449569
- Yang ML, Gee AJ, Gee RJ, Zurita-Lopez CI, Khare S, Clarke SG, Mamula MJ: Lupus autoimmunity altered by cellular methylation metabolism. Autoimmunity. 2013 Feb; 2012 Nov 1. PMID: 23039363
- Doyle HA, Aswad DW, Mamula MJ: Autoimmunity to isomerized histone H2B in systemic lupus erythematosus. Autoimmunity. 2013 Feb; 2012 Dec 3. PMID: 22967069
- Raycroft MT, Harvey BP, Bruck MJ, Mamula MJ: Inhibition of antigen trafficking through scavenger receptor A. J Biol Chem. 2012 Feb 17; 2012 Jan 3. PMID: 22215667
- Doyle HA, Mamula MJ: Autoantigenesis: the evolution of protein modifications in autoimmune disease. Curr Opin Immunol. 2012 Feb; 2011 Dec 29. PMID: 22209691
- Zhang J, Ge R, Matte-Martone C, Goodwin J, Shlomchik WD, Mamula MJ, Kooshkabadi A, Hardy MP, Geller D: Characterization of a novel gain of function glucocorticoid receptor knock-in mouse. J Biol Chem. 2009 Mar 6; 2008 Nov 18. PMID: 19017639
- Harvey BP, Quan TE, Rudenga BJ, Roman RM, Craft J, Mamula MJ: Editing antigen presentation: antigen transfer between human B lymphocytes and macrophages mediated by class A scavenger receptors. J Immunol. 2008 Sep 15. PMID: 18768860
- Harvey BP, Gee RJ, Haberman AM, Shlomchik MJ, Mamula MJ: Antigen presentation and transfer between B cells and macrophages. Eur J Immunol. 2007 Jul. PMID: 17534863
- Doyle HA, Gee RJ, Mamula MJ: Altered immunogenicity of isoaspartate containing proteins. Autoimmunity. 2007 Mar. PMID: 17453712
- Doyle HA, Zhou J, Wolff MJ, Harvey BP, Roman RM, Gee RJ, Koski RA, Mamula MJ: Isoaspartyl post-translational modification triggers anti-tumor T and B lymphocyte immunity. J Biol Chem. 2006 Oct 27; 2006 Sep 1. PMID: 16950786
- Yang ML, Doyle HA, Gee RJ, Lowenson JD, Clarke S, Lawson BR, Aswad DW, Mamula MJ: Intracellular protein modification associated with altered T cell functions in autoimmunity. J Immunol. 2006 Oct 1. PMID: 16982891
- Yan J, Harvey BP, Gee RJ, Shlomchik MJ, Mamula MJ: B cells drive early T cell autoimmunity in vivo prior to dendritic cell-mediated autoantigen presentation. J Immunol. 2006 Oct 1. PMID: 16982884
- Mamula MJ, Farber DL, Tsokos GC: Autoimmune odyssey on the Aegean Sea. Nat Immunol. 2006 Mar. PMID: 16482164
- Yan J, Wolff MJ, Unternaehrer J, Mellman I, Mamula MJ: Targeting antigen to CD19 on B cells efficiently activates T cells. Int Immunol. 2005 Jul; 2005 Jun 20. PMID: 15967786
- Doyle HA, Mamula MJ: Posttranslational modifications of self-antigens. Ann N Y Acad Sci. 2005 Jun. PMID: 16014515
- Doyle HA, Gee RJ, Mamula MJ: A failure to repair self-proteins leads to T cell hyperproliferation and autoantibody production. J Immunol. 2003 Sep 15. PMID: 12960305
- Yan J, Mamula MJ: B and T cell tolerance and autoimmunity in autoantibody transgenic mice. Int Immunol. 2002 Aug. PMID: 12147633
- Zhou J, Zhang JS, Ma BL, Mamula MJ: Experimental autoimmune encephalomyelitis in the Wistar rat: dependence of MBP-specific T cell responsiveness on B7 costimulation. Autoimmunity. 2002 May. PMID: 12389644
- Doyle HA, Mamula MJ: Posttranslational protein modifications: new flavors in the menu of autoantigens. Curr Opin Rheumatol. 2002 May. PMID: 11981321
- Yan J, Mamula MJ: Autoreactive T cells revealed in the normal repertoire: escape from negative selection and peripheral tolerance. J Immunol. 2002 Apr 1. PMID: 11907071