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

Photo of Michael B. Brenner, MD

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


mbrenner@rics.bwh.harvard.edu

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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 from Harvard Catalyst Profiles

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  • Davidson S, Coles M, Thomas T, Kollias G, Ludewig B, Turley S, Brenner M, Buckley CD. Fibroblasts as immune regulators in infection, inflammation and cancer. Nat Rev Immunol 2021. PubMed
  • Lopes N, McIntyre C, Martin S, Raverdeau M, Sumaria N, Kohlgruber AC, Fiala GJ, Agudelo LZ, Dyck L, Kane H, Douglas A, Cunningham S, Prendeville H, Loftus R, Carmody C, Pierre P, Kellis M, Brenner M, Argüello RJ, Silva-Santos B, Pennington DJ, Lynch L. Distinct metabolic programs established in the thymus control effector functions of γδ T cell subsets in tumor microenvironments. Nat Immunol 2021; 22:179-192. PubMed
  • LaMarche NM, Kane H, Kohlgruber AC, Dong H, Lynch L, Brenner MB. Distinct iNKT Cell Populations Use IFNγ or ER Stress-Induced IL-10 to Control Adipose Tissue Homeostasis. Cell Metab 2020. PubMed
  • Donado CA, Cao AB, Simmons DP, Croker BA, Brennan PJ, Brenner MB. A Two-Cell Model for IL-1β Release Mediated by Death-Receptor Signaling. Cell Rep 2020; 31:107466. PubMed
  • Clancy-Thompson E, Chen GZ, LaMarche NM, Ali LR, Jeong HJ, Crowley SJ, Boelaars K, Brenner MB, Lynch L, Dougan SK. Transnuclear mice reveal Peyer's patch iNKT cells that regulate B-cell class switching to IgG1. EMBO J 2019; 38:e101260. PubMed
  • Madarampalli B, Watts GFM, Panipinto PM, Nguygen HN, Brenner MB, Noss EH. Interactions between cadherin-11 and platelet-derived growth factor receptor-alpha signaling link cell adhesion and proliferation. Biochim Biophys Acta Mol Basis Dis 2019. PubMed
  • Gutierrez-Arcelus M, Teslovich N, Mola AR, Polidoro RB, Nathan A, Kim H, Hannes S, Slowikowski K, Watts GFM, Korsunsky I, Brenner MB, Raychaudhuri S, Brennan PJ. Lymphocyte innateness defined by transcriptional states reflects a balance between proliferation and effector functions. Nat Commun 2019; 10:687. PubMed
  • Michelet X, Dyck L, Hogan A, Loftus RM, Duquette D, Wei K, Beyaz S, Tavakkoli A, Foley C, Donnelly R, O'Farrelly C, Raverdeau M, Vernon A, Pettee W, O'Shea D, Nikolajczyk BS, Mills KHG, Brenner MB, Finlay D, Lynch L. Metabolic reprogramming of natural killer cells in obesity limits antitumor responses. Nat Immunol 2018; 19:1330-1340. PubMed
  • Gansner JM, Rahmani M, Jonsson AH, Fortin BM, Brimah I, Ellis M, Smeland-Wagman R, Li ZJ, Schenkel JM, Brenner MB, Yefidoff-Freedman R, Sloan SR, Berliner N, Issa NC, Baden LR, Longo DL, Wesemann DR, Neuberg D, Rao DA, Kaufman RM. Plateletpheresis-associated lymphopenia in frequent platelet donors. Blood 2018. PubMed
  • Kohlgruber AC, Gal-Oz ST, LaMarche NM, Shimazaki M, Duquette D, Nguyen HN, Mina AI, Paras T, Tavakkoli A, von Andrian U, Banks AS, Shay T, Brenner MB, Lynch L. γδ T cells producing interleukin-17A regulate adipose regulatory T cell homeostasis and thermogenesis. Nat Immunol 2018; 19:464-474. PubMed
  • Slowikowski K, Wei K, Brenner MB, Raychaudhuri S. Functional genomics of stromal cells in chronic inflammatory diseases. Curr Opin Rheumatol 2017. PubMed
  • Chang SK, Kohlgruber AC, Mizoguchi F, Michelet X, Wolf BJ, Wei K, Lee PY, Lynch L, Duquette D, Ceperuelo-Mallafré V, Banks AS, Brenner MB. Stromal cell cadherin-11 regulates adipose tissue inflammation and diabetes. J Clin Invest 2017; 127:3300-3312. PubMed
  • Boulenouar S, Michelet X, Duquette D, Alvarez D, Hogan AE, Dold C, O'Connor D, Stutte S, Tavakkoli A, Winters D, Exley MA, O'Shea D, Brenner MB, von Andrian U, Lynch L. Adipose Type One Innate Lymphoid Cells Regulate Macrophage Homeostasis through Targeted Cytotoxicity. Immunity 2017; 46:273-286. PubMed
  • Nguyen HN, Noss EH, Mizoguchi F, Huppertz C, Wei KS, Watts GF, Brenner MB. Autocrine Loop Involving IL-6 Family Member LIF, LIF Receptor, and STAT4 Drives Sustained Fibroblast Production of Inflammatory Mediators. Immunity 2017; 46:220-232. PubMed
  • Rao DA, Gurish MF, Marshall JL, Slowikowski K, Fonseka CY, Liu Y, Donlin LT, Henderson LA, Wei K, Mizoguchi F, Teslovich NC, Weinblatt ME, Massarotti EM, Coblyn JS, Helfgott SM, Lee YC, Todd DJ, Bykerk VP, Goodman SM, Pernis AB, Ivashkiv LB, Karlson EW, Nigrovic PA, Filer A, Buckley CD, Lederer JA, Raychaudhuri S, Brenner MB. Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis. Nature 2017; 542:110-114. PubMed
  • Birtolo C, Pham H, Morvaridi S, Chheda C, Go VL, Ptasznik A, Edderkaoui M, Weisman MH, Noss E, Brenner MB, Larson B, Guindi M, Wang Q, Pandol SJ. Cadherin-11 Is a Cell Surface Marker Up-Regulated in Activated Pancreatic Stellate Cells and Is Involved in Pancreatic Cancer Cell Migration. Am J Pathol 2017; 187:146-155. PubMed
  • Encarnação M, Espada L, Escrevente C, Mateus D, Ramalho J, Michelet X, Santarino I, Hsu VW, Brenner MB, Barral D, Vieira OV. A Rab3a-dependent complex essential for lysosome positioning and plasma membrane repair. J Cell Biol 2016; 213:631-40. PubMed
  • Wolf BJ, Tatituri RV, Almeida CF, Le Nours J, Bhowruth V, Johnson D, Uldrich AP, Hsu FF, Brigl M, Besra GS, Rossjohn J, Godfrey DI, Brenner MB. Identification of a Potent Microbial Lipid Antigen for Diverse NKT Cells. J Immunol 2015; 195:2540-51. 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
  • Kim EY, Lynch L, Brennan PJ, Cohen NR, Brenner MB. The transcriptional programs of iNKT cells. Semin Immunol 2015. 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 2015; 16:85-95. PubMed
  • Garg S, Brenner MB. RNAi screens of lysosomal trafficking. Methods Cell Biol. 2015; 126:119-38. 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
  • Jojic V, Shay T, Sylvia K, Zuk O, Sun X, Kang J, Regev A, Koller D, , Best AJ, Knell J, Goldrath A, Joic 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, Bellemarte-Pelletier A, Malhotra D, Turley S. Identification of transcriptional regulators in the mouse immune system. Nat Immunol 2013. PubMed
  • Mingueneau M, Kreslavsky T, Gray D, Heng T, Cruse R, Ericson J, Bendall S, Spitzer MH, Nolan GP, Kobayashi K, von Boehmer H, Mathis D, Benoist C, , Best AJ, Knell J, Goldrath A, Joic V, Koller D, Shay T, Regev A, Cohen N, Brennan P, Brenner M, Kim F, Nageswara Rao T, 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 αβ T cell differentiation. 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 2013; 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
  • 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
  • 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
  • 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 2009; 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 2008; 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
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DF/HCC members that share similar concepts* with Michael B. Brenner, MD but have yet to coauthor a publication with this researcher.

* Concepts are MeSH terms, automatically derived from member publications

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