Photo of Michael B. Brenner,  MD

Michael B. Brenner, MD

Brigham And Women's Hospital

Brigham And Women's Hospital
Phone: (617) 525-1000
Fax: (617) 525-1001


mbrenner@rics.bwh.harvard.edu

Michael B. Brenner, MD

Brigham And Women's Hospital

EDUCATIONAL TITLES

  • Theodore Bevier Bayles Professor of Medicine, Medicine, Harvard Medical School
  • Chief, Rheumatology, Immunology and Allergy, Brigham And Women's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

This laboratory studies T lymphocyte biology with emphasis on antigen presentation, T cell receptor recognition, and lymphocyte homing and trafficking. We demonstrated that immune system T cells are capable of recognizing non-protein lipid and glycolipid antigens presented in the context of CD1 molecules. Thus, the paradigm that T cells recognize only peptide antigens in the context of MHC has been extended to reveal a further universe of foreign and self nonprotein antigens that are recognized in a CD1 restricted manner. Foreign microbial lipids and glycolipids are being studied in the context of vaccine development as their recognition plays an important role in eliciting a previously unappreciated component of T cell immunity in host defense. Studies on recognition of tumor glycolipids and the role of CD1 reactive NKT cells in tumor immunity are also being investigated.

In addition, we are studying the role of cadherins in cell biology and cancer. Cadherins are cell adhesion and signaling molecules that are responsible for the morphogenesis of tissues during development and for their organization and integrity in adults. In addition, cadherins are critical molecules in cell transformation and cell behavior in cancer. We have found that a mesenchymal cadherin, cadherin-11, markedly enhances the migration and invasion of tumor cells. We are developing the reagents that block this molecule and reverse the increased invasiveness it mediates.

Publications

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  • Kim EY, Lynch L, Brennan PJ, Cohen NR, Brenner MB. The transcriptional programs of iNKT cells. Semin Immunol 2015. PubMed
  • Michelet X, Garg S, Wolf BJ, Tuli A, Ricciardi-Castagnoli P, Brenner MB. MHC class II presentation is controlled by the lysosomal small GTPase, Arl8b. J Immunol 2015; 194:2079-88. PubMed
  • Garg S, Brenner MB. RNAi screens of lysosomal trafficking. Methods Cell Biol. 2015; 126:119-38. PubMed
  • Lynch L, Michelet X, Zhang S, Brennan PJ, Moseman A, Lester C, Besra G, Vomhof-Dekrey EE, Tighe M, Koay HF, Godfrey DI, Leadbetter EA, Sant'Angelo DB, von Andrian U, Brenner MB. Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of T(reg) cells and macrophages in adipose tissue. Nat Immunol 2014; 16:85-95. PubMed
  • Brennan PJ, Tatituri RV, Heiss C, Watts GF, Hsu FF, Veerapen N, Cox LR, Azadi P, Besra GS, Brenner MB. Activation of iNKT cells by a distinct constituent of the endogenous glucosylceramide fraction. Proc Natl Acad Sci U S A 2014; 111:13433-8. PubMed
  • Wu M, Pedroza M, Lafyatis R, George AT, Mayes MD, Assassi S, Tan FK, Brenner MB, Agarwal SK. Identification of cadherin 11 as a mediator of dermal fibrosis and possible role in systemic sclerosis. 2014; 66:1010-21. PubMed
  • Gu Z, Liu F, Tonkova EA, Lee SY, Tschumperlin DJ, Brenner MB. Soft matrix is a natural stimulator for cellular invasiveness. Mol Biol Cell 2014; 25:457-69. PubMed
  • Bassiri H, Das R, Guan P, Barrett DM, Brennan PJ, Banerjee PP, Wiener SJ, Orange JS, Brenner MB, Grupp SA, Nichols KE. iNKT cell cytotoxic responses control T-lymphoma growth in vitro and in vivo. Cancer Immunol Res 2014; 2:59-69. PubMed
  • Tuli A, Thiery J, James AM, Michelet X, Sharma M, Garg S, Sanborn KB, Orange JS, Lieberman J, Brenner MB. Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell-mediated cytotoxicity. Mol Biol Cell 2013; 24:3721-35. PubMed
  • Hu X, Kim H, Brennan PJ, Han B, Baecher-Allan CM, De Jager PL, Brenner MB, Raychaudhuri S. Application of user-guided automated cytometric data analysis to large-scale immunoprofiling of invariant natural killer T cells. Proc Natl Acad Sci U S A 2013; 110:19030-5. PubMed
  • Wu M, Pedroza M, Lafyatis R, George AT, Mayes MD, Assassi S, Tan FK, Brenner MB, Agarwal SK. Identification of cadherin-11 as a mediator of dermal fibrosis and possible role in systemic sclerosis. Arthritis Rheum 2013. PubMed
  • Mingueneau M, Kreslavsky T, Gray D, Heng T, Cruse R, Ericson J, Bendall S, Spitzer M, Nolan G, Kobayashi K, von Boehmer H, Mathis D, Benoist C, , Best AJ, Knell J, Goldrath A, Jojic V, Koller D, Shay T, Regev A, Cohen N, Brennan P, Brenner M, Kim F, Rao TN, Wagers A, Heng T, Ericson J, Rothamel K, Ortiz-Lopez A, Mathis D, Benoist C, Bezman NA, Sun JC, Min-Oo G, Kim CC, Lanier LL, Miller J, Brown B, Merad M, Gautier EL, Jakubzick C, Randolph GJ, Monach P, Blair DA, Dustin ML, Shinton SA, Hardy RR, Laidlaw D, Collins J, Gazit R, Rossi DJ, Malhotra N, Sylvia K, Kang J, Kreslavsky T, Fletcher A, Elpek K, Bellemare-Pelletier A, Malhotra D, Turley S. The transcriptional landscape of 留硫 T cell differentiation. Nat Immunol 2013. PubMed
  • Jojic V, Shay T, Sylvia K, Zuk O, Sun X, Kang J, Regev A, Koller D, , Best AJ, Knell J, Goldrath A, Jojic V, Koller D, Shay T, Regev A, Cohen N, Brennan P, Brenner M, Kim F, Rao TN, Wagers A, Heng T, Ericson J, Rothamel K, Ortiz-Lopez A, Mathis D, Benoist C, Bezman NA, Sun JC, Min-Oo G, Kim CC, Lanier LL, Miller J, Brown B, Merad M, Gautier EL, Jakubzick C, Randolph GJ, Monach P, Blair DA, Dustin ML, Shinton SA, Hardy RR, Laidlaw D, Collins J, Gazit R, Rossi DJ, Malhotra N, Sylvia K, Kang J, Kreslavsky T, Fletcher A, Elpek K, Bellemare-Pelletier A, Malhotra D, Turley S. Identification of transcriptional regulators in the mouse immune system. Nat Immunol 2013. PubMed
  • Sanderson JP, Brennan PJ, Mansour S, Matulis G, Patel O, Lissin N, Godfrey DI, Kawahara K, Zähringer U, Rossjohn J, Brenner MB, Gadola SD. CD1d protein structure determines species-selective antigenicity of isoglobotrihexosylceramide (iGb3) to invariant NKT cells. Eur J Immunol 2013; 43:815-25. PubMed
  • Tatituri RV, Watts GF, Bhowruth V, Barton N, Rothchild A, Hsu FF, Almeida CF, Cox LR, Eggeling L, Cardell S, Rossjohn J, Godfrey DI, Behar SM, Besra GS, Brenner MB, Brigl M. Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs. Proc Natl Acad Sci U S A 2013; 110:1827-32. PubMed
  • Cohen NR, Brennan PJ, Shay T, Watts GF, Brigl M, Kang J, Brenner MB, . Shared and distinct transcriptional programs underlie the hybrid nature of iNKT cells. Nat Immunol 2012; 14:90-9. PubMed
  • Barral DC, Garg S, Casalou C, Watts GF, Sandoval JL, Ramalho JS, Hsu VW, Brenner MB. Arl13b regulates endocytic recycling traffic. Proc Natl Acad Sci U S A 2012; 109:21354-9. PubMed
  • Veerapen N, Leadbetter EA, Brenner MB, Cox LR, Besra GS. Synthesis of a novel alpha-galactosyl ceramide haptenated-lipid antigen, a useful tool in demonstrating the involvement of iNKT cells in the production of antilipid antibodies. Bioconjug Chem 2010; 21:741-7. PubMed
  • Odyniec AN, Barral DC, Garg S, Tatituri RV, Besra GS, Brenner MB. Regulation of CD1 antigen presenting complex stability. J Biol Chem 2010; 285:11937-47. PubMed
  • Brigl M, Brenner MB. How invariant natural killer T cells respond to infection by recognizing microbial or endogenous lipid antigens. Semin Immunol 2010; 22:79-86. PubMed
  • Porcelli S, Brenner MB, Greenstein JL, Terhorst C, Balk SP, Bleicher PA. Pillars Article: Recognition of Cluster of Differentiation 1 Antigens by Human CD4-CD8- CytolyticT Lymphocyte. Nature. 1989. 341: 447-450. J Immunol 2010; 184:3306-9. PubMed
  • Kiener HP, Watts GF, Cui Y, Wright J, Thornhill TS, Sköld M, Behar SM, Niederreiter B, Lu J, Cernadas M, Coyle AJ, Sims GP, Smolen J, Warman ML, Brenner MB, Lee DM. Synovial fibroblasts self-direct multicellular lining architecture and synthetic function in three-dimensional organ culture. Arthritis Rheum 2010; 62:742-52. PubMed
  • Muindi K, Cernadas M, Watts GF, Royle L, Neville DC, Dwek RA, Besra GS, Rudd PM, Butters TD, Brenner MB. Activation state and intracellular trafficking contribute to the repertoire of endogenous glycosphingolipids presented by CD1d. Proc Natl Acad Sci U S A 2010; 107:3052-7. PubMed
  • Cernadas M, Cavallari M, Watts G, Mori L, De Libero G, Brenner MB. Early recycling compartment trafficking of CD1a is essential for its intersection and presentation of lipid antigens. J Immunol 2010; 184:1235-41. PubMed
  • Chiba A, Cohen N, Brigl M, Brennan PJ, Besra GS, Brenner MB. Rapid and reliable generation of invariant natural killer T-cell lines in vitro. Immunology 2010; 128:324-33. PubMed
  • Felio K, Nguyen H, Dascher CC, Choi HJ, Li S, Zimmer MI, Colmone A, Moody DB, Brenner MB, Wang CR. CD1-restricted adaptive immune responses to Mycobacteria in human group 1 CD1 transgenic mice. J Exp Med 2009; 206:2497-509. PubMed
  • Veerapen N, Brigl M, Garg S, Cerundolo V, Cox LR, Brenner MB, Besra GS. Synthesis and biological activity of alpha-galactosyl ceramide KRN7000 and galactosyl (alpha1-->2) galactosyl ceramide. Bioorg Med Chem Lett 2009; 19:4288-91. PubMed
  • Van Rhijn I,Young DC,De Jong A,Vazquez J,Cheng TY,Talekar R,Barral D,Leon L,Brenner MB,Katz JT,Riese R,Ruprecht RM,O'Connor PB,Costello CE,Porcelli SA,Briken V,Moody DB. CD1c bypasses lysosomes to present a lipopeptide antigen with 12 amino acids. J Exp Med 2009; 206:1409-22. PubMed
  • Kiener HP,Niederreiter B,Lee DM,Jimenez-Boj E,Smolen JS,Brenner MB. Cadherin 11 promotes invasive behavior of fibroblast-like synoviocytes. Arthritis Rheum 2009; 60:1305-10. PubMed
  • Cohen NR,Garg S,Brenner MB. Chapter 1 Antigen Presentation by CD1 Lipids, T Cells, and NKT Cells in Microbial Immunity. Adv Immunol 2009; 102:1-94. PubMed
  • Sada-Ovalle I,Chiba A,Gonzales A,Brenner MB,Behar SM. Innate invariant NKT cells recognize Mycobacterium tuberculosis-infected macrophages, produce interferon-gamma, and kill intracellular bacteria. PLoS Pathog 2008; 4:e1000239. PubMed
  • Leslie DS, Dascher CC, Cembrola K, Townes MA, Hava DL, Hugendubler LC, Mueller E, Fox L, Roura-Mir C, Moody DB, Vincent MS, Gumperz JE, Illarionov PA, Besra GS, Reynolds CG, Brenner MB. Serum lipids regulate dendritic cell CD1 expression and function. Immunology 2009; 125:289-301. PubMed
  • Barral DC,Cavallari M,McCormick PJ,Garg S,Magee AI,Bonifacino JS,De Libero G,Brenner MB. CD1a and MHC class I follow a similar endocytic recycling pathway. Traffic 2008; 9:1446-57. PubMed
  • Hava DL,van der Wel N,Cohen N,Dascher CC,Houben D,Leon L,Agarwal S,Sugita M,van Zon M,Kent SC,Shams H,Peters PJ,Brenner MB. Evasion of peptide, but not lipid antigen presentation, through pathogen-induced dendritic cell maturation. Proc Natl Acad Sci U S A 2008; 105:11281-6. PubMed
  • Kaser A,Hava DL,Dougan SK,Chen Z,Zeissig S,Brenner MB,Blumberg RS. Microsomal triglyceride transfer protein regulates endogenous and exogenous antigen presentation by group 1 CD1 molecules. Eur J Immunol 2008; 38:2351-9. PubMed
  • Leadbetter EA,Brigl M,Illarionov P,Cohen N,Luteran MC,Pillai S,Besra GS,Brenner MB. NK T cells provide lipid antigen-specific cognate help for B cells. Proc Natl Acad Sci U S A 2008; 105:8339-44. PubMed
  • Noss EH,Brenner MB. The role and therapeutic implications of fibroblast-like synoviocytes in inflammation and cartilage erosion in rheumatoid arthritis. Immunol Rev 2008; 223:252-70. PubMed
  • Barral DC, Brenner MB. CD1 antigen presentation: how it works. Nat Rev Immunol 2007; 7:929-41. PubMed
  • Milo R, Hou JH, Springer M, Brenner MP, Kirschner MW. The relationship between evolutionary and physiological variation in hemoglobin. Proc Natl Acad Sci U S A 2007; 104:16998-7003. PubMed
  • Parisini E, Higgins JM, Liu JH, Brenner MB, Wang JH. The crystal structure of human E-cadherin domains 1 and 2, and comparison with other cadherins in the context of adhesion mechanism. J Mol Biol 2007; 373:401-11. PubMed
  • Lee DM, Kiener HP, Agarwal SK, Noss EH, Watts GF, Chisaka O, Takeichi M, Brenner MB. Cadherin-11 in synovial lining formation and pathology in arthritis. Science 2007; 315:1006-10. PubMed
  • Kiener HP, Stipp CS, Allen PG, Higgins JM, Brenner MB. The cadherin-11 cytoplasmic juxtamembrane domain promotes alpha-catenin turnover at adherens junctions and intercellular motility. Mol Biol Cell 2006; 17:2366-76. PubMed
  • van den Elzen P, Garg S, Le. Apolipoprotein-mediated pathways of lipid antigen presentation. Nature 2005; 437:906-10. PubMed
  • Moody DB, Young DC, Cheng TY, Rosat JP, Roura-Mir C, O'Connor PB, Zajonc DM, Walz A, Miller MJ, Levery SB, Wilson IA, Costello CE, Brenner MB. T cell activation by lipopeptide antigens. Science 2004; 303:527-31. PubMed
  • Brigl M, Bry L, Kent SC, Gumperz JE, Brenner MB. Mechanism of CD1d-restricted natural killer T cell activation during microbial infection. Nat Immunol 2003; 4:1230-7. PubMed
  • Vincent MS, Leslie DS, Gumperz JE, Xiong X, Grant EP, Brenner MB. CD1-dependent dendritic cell instruction. Nat Immunol 2002; 3:1163-8. PubMed
  • Moody DB, Ulrichs T, M. CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection. Nature 2000; 404:884-8. PubMed
  • Sugita M, Grant EP, van Donselaar E, Hsu VW, Rogers RA, Peters PJ, Brenner MB. Separate pathways for antigen presentation by CD1 molecules. Immunity 2000; 11:743-52. PubMed
  • Higgins JM, Mandlebrot DA, Shaw SK, Russell GJ, Murphy EA, Chen YT, Nelson WJ, Parker CM, Brenner MB. Direct and regulated interaction of integrin alphaEbeta7 with E-cadherin. J Cell Biol 1998; 140:197-210. PubMed
  • Beckman EM, Porcelli SA, Morita CT, Behar SM, Furlong ST, Brenner MB. Recognition of a lipid antigen by CD1-restricted alpha beta+ T cells. Nature 1994; 372:691-4. PubMed
  • Cepek KL, Shaw SK, Parker CM, Russell GJ, Morrow JS, Rimm DL, Brenner MB. Adhesion between epithelial cells and T lymphocytes mediated by E-cadherin and the alpha E beta 7 integrin. Nature 1994; 372:190-3. PubMed
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