Photo of Diane J. Mathis,  PhD

Diane J. Mathis, PhD

Harvard Medical School

Harvard Medical School
Phone: (617) 432-7742
Fax: (617) 432-0774


dm@hms.harvard.edu

Diane J. Mathis, PhD

Harvard Medical School

EDUCATIONAL TITLES

  • Morton Grove-Rasmussen Professor of Immunohematology, Microbiology and Immunobiology, Harvard Medical School
  • Division Head, Microbiology and Immunobiology; Division of Immunobiology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

Our lab works in the fields of T cell differentiation and autoimmunity, with a special emphasis on exploiting the most advanced transgenic and gene-targeting technology to engineer new mouse models. Studies on T cell differentiation focus on selection of the T cell repertoire in the thymus and cellular and molecular influences on T cell survival in the periphery. Studies on autoimmunity explore the immunological mechanisms of diabetes, rheumatoid arthritis and APECED. Major questions tackled are what initiates these diseases, how is their progression regulated, and what are the final effector mechanisms. In addition, modern genetic and genomic approaches are used to identify disease-modifying genes in both human patients and mouse models. The application of computational and bioinformatic strategies to these and other issues is actively pursued. Lastly, we have been engaged in a collaborative effort to develop and apply novel whole-mouse imaging strategies to immunological problems.

Publications

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  • Yang S, Fujikado N, Kolodin D, Benoist C, Mathis D. Regulatory T cells generated early in life play a distinct role in maintaining self-tolerance. Science 2015. PubMed
  • Mingueneau M, Krishnaswamy S, Spitzer MH, Bendall SC, Stone EL, Hedrick SM, Pe'er D, Mathis D, Nolan GP, Benoist C. Single-cell mass cytometry of TCR signaling: amplification of small initial differences results in low ERK activation in NOD mice. Proc Natl Acad Sci U S A 2014; 111:16466-71. PubMed
  • Mostafavi S, Ortiz-Lopez A, Bogue MA, Hattori K, Pop C, Koller D, Mathis D, Benoist C, , Blair DA, Dustin ML, Shinton SA, Hardy RR, 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, Kreslavsky T, Fletcher A, Elpek K, Bellemare-Pelletier A, Malhotra D, Turley S, Miller J, Brown B, Merad M, Gautier EL, Jakubzick C, Randolph GJ, Monach P, Best AJ, Knell J, Goldrath A, Jojic V, Koller D, Laidlaw D, Collins J, Gazit R, Rossi DJ, Malhotra N, Sylvia K, Kang J, Bezman NA, Sun JC, Min-Oo G, Kim CC, Lanier LL. Variation and Genetic Control of Gene Expression in Primary Immunocytes across Inbred Mouse Strains. J Immunol 2014; 193:4485-96. PubMed
  • Joller N, Lozano E, Burkett PR, Patel B, Xiao S, Zhu C, Xia J, Tan TG, Sefik E, Yajnik V, Sharpe AH, Quintana FJ, Mathis D, Benoist C, Hafler DA, Kuchroo VK. Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses. Immunity 2014; 40:569-81. PubMed
  • Giraud M, Jmari N, Du L, Carallis F, Nieland TJ, Perez-Campo FM, Bensaude O, Root DE, Hacohen N, Mathis D, Benoist C. An RNAi screen for Aire cofactors reveals a role for Hnrnpl in polymerase release and Aire-activated ectopic transcription. Proc Natl Acad Sci U S A 2014; 111:1491-6. PubMed
  • Cohen P, Levy JD, Zhang Y, Frontini A, Kolodin DP, Svensson KJ, Lo JC, Zeng X, Ye L, Khandekar MJ, Wu J, Gunawardana SC, Banks AS, Camporez JP, Jurczak MJ, Kajimura S, Piston DW, Mathis D, Cinti S, Shulman GI, Seale P, Spiegelman BM. Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell 2014; 156:304-16. PubMed
  • Fu W, Farache J, Clardy SM, Hattori K, Mander P, Lee K, Rioja I, Weissleder R, Prinjha RK, Benoist C, Mathis D. Epigenetic modulation of type-1 diabetes via a dual effect on pancreatic macrophages and 硫 cells. Elife 2014; 3:e04631. PubMed
  • Ergun A, Doran G, Costello JC, Paik HH, Collins JJ, Mathis D, Benoist C, . Differential splicing across immune system lineages. Proc Natl Acad Sci U S A 2013; 110:14324-9. PubMed
  • Sitrin J, Ring A, Garcia KC, Benoist C, Mathis D. Regulatory T cells control NK cells in an insulitic lesion by depriving them of IL-2. J Exp Med 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
  • Abbas AK, Benoist C, Bluestone JA, Campbell DJ, Ghosh S, Hori S, Jiang S, Kuchroo VK, Mathis D, Roncarolo MG, Rudensky A, Sakaguchi S, Shevach EM, Vignali DA, Ziegler SF. Regulatory T cells: recommendations to simplify the nomenclature. Nat Immunol 2013; 14:307-8. PubMed
  • Wakamatsu E, Mathis D, Benoist C. Convergent and divergent effects of costimulatory molecules in conventional and regulatory CD4+ T cells. Proc Natl Acad Sci U S A 2013; 110:1023-8. PubMed
  • Benoist C, Lanier L, Merad M, Mathis D, . Consortium biology in immunology: the perspective from the Immunological Genome Project. Nat Rev Immunol 2012; 12:734-40. PubMed
  • Fu W, Ergun A, Lu T, Hill JA, Haxhinasto S, Fassett MS, Gazit R, Adoro S, Glimcher L, Chan S, Kastner P, Rossi D, Collins JJ, Mathis D, Benoist C. A multiply redundant genetic switch 'locks in' the transcriptional signature of regulatory T cells. Nat Immunol 2012; 13:972-80. PubMed
  • Gautier EL, Shay T, Miller J, Greter M, Jakubzick C, Ivanov S, Helft J, Chow A, Elpek KG, Gordonov S, Mazloom AR, Ma'ayan A, Chua WJ, Hansen TH, Turley SJ, Merad M, Randolph GJ, , Gautier EL, Jakubzick C, Randolph GJ, Best AJ, Knell J, Goldrath A, Miller J, Brown B, Merad M, Jojic V, Koller D, Cohen N, Brennan P, Brenner M, Shay T, Regev A, Fletcher A, Elpek K, Bellemare-Pelletier A, Malhotra D, Turley S, Jianu R, Laidlaw D, Collins J, Narayan K, Sylvia K, Kang J, Gazit R, Garrison BS, Rossi DJ, Kim F, Rao TN, Wagers A, Shinton SA, Hardy RR, Monach P, Bezman NA, Sun JC, Kim CC, Lanier LL, Heng T, Kreslavsky T, Painter M, Ericson J, Davis S, Mathis D, Benoist C. Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat Immunol 2012; 13:1118-1128. PubMed
  • Benoist C, Mathis D. Treg cells, life history, and diversity. Cold Spring Harb Perspect Biol 2012; 4:a007021. PubMed
  • Bandukwala HS, Wu Y, Feurer M, Chen Y, Barbosa B, Ghosh S, Stroud JC, Benoist C, Mathis D, Rao A, Chen L. Structure of a Domain-Swapped FOXP3 Dimer on DNA and Its Function in Regulatory T Cells. Immunity 2011. PubMed
  • Painter MW, Davis S, Hardy RR, Mathis D, Benoist C, . Transcriptomes of the B and T lineages compared by multiplatform microarray profiling. J Immunol 2011; 186:3047-57. PubMed
  • Rubtsov YP, Niec RE, Josefowicz S, Li L, Darce J, Mathis D, Benoist C, Rudensky AY. Stability of the regulatory T cell lineage in vivo. Science 2010; 329:1667-71. PubMed
  • Nishio J, Feuerer M, Wong J, Mathis D, Benoist C. Anti-CD3 therapy permits regulatory T cells to surmount T cell receptor-specified peripheral niche constraints. J Exp Med 2010; 207:1879-89. PubMed
  • Koh AS, Kingston RE, Benoist C, Mathis D. Global relevance of Aire binding to hypomethylated lysine-4 of histone-3. Proc Natl Acad Sci U S A 2010; 107:13016-21. PubMed
  • Feuerer M, Hill JA, Kretschmer K, von Boehmer H, Mathis D, Benoist C. Genomic definition of multiple ex vivo regulatory T cell subphenotypes. Proc Natl Acad Sci U S A 2010; 107:5919-24. PubMed
  • Monach PA, Nigrovic PA, Chen M, Hock H, Lee DM, Benoist C, Mathis D. Neutrophils in a mouse model of autoantibody-mediated arthritis: critical producers of Fc receptor gamma, the receptor for C5a, and lymphocyte function-associated antigen 1. Arthritis Rheum 2010; 62:753-64. PubMed
  • Abramson J, Giraud M, Benoist C, Mathis D. Aire's partners in the molecular control of immunological tolerance. Cell 2010; 140:123-35. PubMed
  • Mathis D, Benoist C. Levees of immunological tolerance. Nat Immunol 2009; 11:3-6. PubMed
  • Yalcin B, Nicod J, Bhomra A, Davidson S, Cleak J, Farinelli L, Østerås M, Whitley A, Yuan W, Gan X, Goodson M, Klenerman P, Satpathy A, Mathis D, Benoist C, Adams DJ, Mott R, Flint J. Commercially available outbred mice for genome-wide association studies. PLoS Genet. 2010. PubMed
  • Huang GJ, Smith AL, Gray DH, Cosgrove C, Singer BH, Edwards A, Sim S, Parent JM, Johnsen A, Mott R, Mathis D, Klenerman P, Benoist C, Flint J. A genetic and functional relationship between T cells and cellular proliferation in the adult hippocampus. PLoS Biol. 2010; 8:e1000561. PubMed
  • Stangenberg L, Ellson C, Cortez-Retamozo V, Ortiz-Lopez A, Yuan H, Blois J, Smith RA, Yaffe MB, Weissleder R, Benoist C, Mathis D, Josephson L, Mahmood U. Abrogation of antibody-induced arthritis in mice by a self-activating viridin prodrug and association with impaired neutrophil and endothelial cell function. Arthritis Rheum 2009; 60:2314-24. PubMed
  • Feuerer M, Hill JA, Mathis D, Benoist C. Foxp3+ regulatory T cells: differentiation, specification, subphenotypes. Nat Immunol 2009; 10:689-95. PubMed
  • D'Alise AM,Auyeung V,Feuerer M,Nishio J,Fontenot J,Benoist C,Mathis D. The defect in T-cell regulation in NOD mice is an effect on the T-cell effectors. Proc Natl Acad Sci U S A 2008; 105:19857-62. PubMed
  • Nigrovic PA,Gray DH,Jones T,Hallgren J,Kuo FC,Chaletzky B,Gurish M,Mathis D,Benoist C,Lee DM. Genetic inversion in mast cell-deficient (W(sh)) mice interrupts corin and manifests as hematopoietic and cardiac aberrancy. Am J Pathol 2008; 173:1693-701. PubMed
  • Hill JA,Hall JA,Sun CM,Cai Q,Ghyselinck N,Chambon P,Belkaid Y,Mathis D,Benoist C. Retinoic acid enhances Foxp3 induction indirectly by relieving inhibition from CD4+CD44hi Cells. Immunity 2008; 29:758-70. PubMed
  • Venanzi ES,Melamed R,Mathis D,Benoist C. The variable immunological self: genetic variation and nongenetic noise in Aire-regulated transcription. Proc Natl Acad Sci U S A 2008; 105:15860-5. PubMed
  • Villasenor J,Besse W,Benoist C,Mathis D. Ectopic expression of peripheral-tissue antigens in the thymic epithelium: probabilistic, monoallelic, misinitiated. Proc Natl Acad Sci U S A 2008; 105:15854-9. PubMed
  • Koh AS,Kuo AJ,Park SY,Cheung P,Abramson J,Bua D,Carney D,Shoelson SE,Gozani O,Kingston RE,Benoist C,Mathis D. Aire employs a histone-binding module to mediate immunological tolerance, linking chromatin regulation with organ-specific autoimmunity. Proc Natl Acad Sci U S A 2008; 105:15878-83. PubMed
  • Guerau-de-Arellano M,Mathis D,Benoist C. Transcriptional impact of Aire varies with cell type. Proc Natl Acad Sci U S A 2008; 105:14011-6. PubMed
  • Gavanescu I,Benoist C,Mathis D. B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients. Proc Natl Acad Sci U S A 2008; 105:13009-14. PubMed
  • Haxhinasto S, Mathis D, Benoist C. The AKT-mTOR axis regulates de novo differentiation of CD4+Foxp3+ cells. J Exp Med 2008; 205:565-74. PubMed
  • Feuerer M, Jiang W, Holler PD, Satpathy A, Campbell C, Bogue M, Mathis D, Benoist C. Enhanced thymic selection of FoxP3+ regulatory T cells in the NOD mouse model of autoimmune diabetes. Proc Natl Acad Sci U S A 2007; 104:18181-6. PubMed
  • Hill JA, Feuerer M, Tash K, Haxhinasto S, Perez J, Melamed R, Mathis D, Benoist C. Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature. Immunity 2007; 27:786-800. PubMed
  • Gray D, Abramson J, Benoist C, Mathis D. Proliferative arrest and rapid turnover of thymic epithelial cells expressing Aire. J Exp Med 2007; 204:2521-8. PubMed
  • Obst R, van Santen HM, Melamed R, Kamphorst AO, Benoist C, Mathis D. Sustained antigen presentation can promote an immunogenic T cell response, like dendritic cell activation. Proc Natl Acad Sci U S A 2007; 104:15460-5. PubMed
  • Wong J, Mathis D, Benoist C. TCR-based lineage tracing: no evidence for conversion of conventional into regulatory T cells in response to a natural self-antigen in pancreatic islets. J Exp Med 2007; 204:2039-45. PubMed
  • Wu HJ, Sawaya H, Binstadt B, Brickelmaier M, Blasius A, Gorelik L, Mahmood U, Weissleder R, Carulli J, Benoist C, Mathis D. Inflammatory arthritis can be reined in by CpG-induced DC-NK cell cross talk. J Exp Med 2007; 204:1911-22. PubMed
  • Wong J, Obst R, Correia-Neves M, Losyev G, Mathis D, Benoist C. Adaptation of TCR Repertoires to Self-Peptides in Regulatory and Nonregulatory CD4+ T Cells. J Immunol 2007; 178:7032-7041. PubMed
  • Nguyen LT, Jacobs J, Mathis D, Benoist C. Where FoxP3-dependent regulatory T cells impinge on the development of inflammatory arthritis. Arthritis Rheum 2007; 56:509-20. PubMed
  • Butty V, Roy M, Sabeti P, Besse W, Benoist C, Mathis D. Signatures of strong population differentiation shape extended haplotypes across the human CD28, CTLA4, and ICOS costimulatory genes. Proc Natl Acad Sci U S A 2007; 104:570-5. PubMed
  • Chen Z, Stockton J, Mathis D, Benoist C. Modeling CTLA4-linked autoimmunity with RNA interference in mice. Proc Natl Acad Sci U S A 2006; 103:16400-5. PubMed
  • Wu Y, Borde M, Heissmeyer V, Feuerer M, Lapan AD, Stroud JC, Bates DL, Guo L, Han A, Ziegler SF, Mathis D, Benoist C, Chen L, Rao A. FOXP3 Controls Regulatory T Cell Function through Cooperation with NFAT. Cell 2006; 126:375-87. PubMed
  • Hyatt G, Melamed R, Park R, Seguritan R, Laplace C, Poirot L, Zucchelli S, Obst R, Matos M, Venanzi E, Goldrath A, Nguyen L, Luckey J, Yamagata T, Herman A, Jacobs J, Mathis D, Benoist C. Gene expression microarrays: glimpses of the immunological genome. Nat Immunol 2006; 7:686-91. PubMed
  • Luckey CJ, Bhattacharya D, Goldrath AW, Weissman IL, Benoist C, Mathis D. Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoietic stem cells. Proc Natl Acad Sci U S A 2006; 103:3304-9. PubMed
  • Chen Z, Herman AE, Matos M, Mathis D, Benoist C. Where CD4+CD25+ T reg cells impinge on autoimmune diabetes. J Exp Med 2005; 202:1387-97. PubMed
  • Obst R, van Santen HM, Mathis D, Benoist C. Antigen persistence is required throughout the expansion phase of a CD4(+) T cell response. J Exp Med 2005; 201:1555-65. PubMed
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