Photo of Laurie H. Glimcher,  MD

Laurie H. Glimcher, MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-4266


Laurie_Glimcher@dfci.harvard.edu

Laurie H. Glimcher, MD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Richard and Susan Smith Professor, Medicine, Harvard Medical School
  • President and CEO, Office of the President, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

DF/HCC ASSOCIATIONS

  • Director, Dana-Farber/Harvard Cancer Center, Executive Committee
  • President, DFCI, Governance Committee
  • Member, Center Scientific Council

Research Abstract

Dr.Glimcher is widely considered to be a world leader in understanding the transcriptional regulation of the cellular differentiation pathways in lymphocytes. She has made seminal discoveries of key transcription factors that drive lineage commitment and activation in the immune system, including the c-Maf and T-bet transcription factors, which regulate a variety of adaptive and innate immune functions in T lymphocytes. In revolutionary work, Dr. Glimcher’s group discovered the first TH1-specific transcription factor, T-bet and demonstrated that this single factor is a master regulator of both IFN-gamma gene expression and the TH1 phenotype. This work overturned the paradigm in the field of cellular immunology that differentiated TH cells are deviated irrevocably in one way or another since T-bet single-handedly could control this critical checkpoint at all stages of differentiation with its attendant therapeutic implications that T cell fate can be directly manipulated. Her laboratory exploited this discovery to create the first mouse model for spontaneous asthma accompanied by chronic airway remodeling, pathognomonic of human asthma, and showed that polymorphisms in the human T-bet gene associate with this disease. She further identified a critical function for T-bet in ulcerative colitis that progresses to colorectal cancer. She also discovered XBP1, the first transcription factor shown to be required for plasma cell differentiation and the mammalian Endoplasmic Reticulum Stress Response. She demonstrated a link between ER stress and proinflammatory/autoimmune diseases in intestinal epithelial cells and in macrophages. Most recently she discovered a key role for XBP1 in both tumor cells and in host immune responses, translating her basic discoveries in the control of immune cell differentiation into a new approach to cancer immunotherapy.

Publications

Powered by Harvard Catalyst
  • Xu Z, Greenblatt MB, Yan G, Feng H, Sun J, Lotinun S, Brady N, Baron R, Glimcher LH, Zou W. SMURF2 regulates bone homeostasis by disrupting SMAD3 interaction with vitamin D receptor in osteoblasts. Nat Commun 2017; 8:14570. PubMed
  • Cubillos-Ruiz JR, Bettigole SE, Glimcher LH. Tumorigenic and Immunosuppressive Effects of Endoplasmic Reticulum Stress in Cancer. Cell 2017; 168:692-706. PubMed
  • Liu CF, Brandt GS, Hoang QQ, Naumova N, Lazarevic V, Hwang ES, Dekker J, Glimcher LH, Ringe D, Petsko GA. Crystal structure of the DNA binding domain of the transcription factor T-bet suggests simultaneous recognition of distant genome sites. Proc Natl Acad Sci U S A 2016; 113:E6572-E6581. PubMed
  • Bettigole SE, Glimcher LH. Novel roles for XBP1 in hematopoietic development. Cell Cycle 2016; 15:1653-4. PubMed
  • Cubillos-Ruiz JR, Silberman PC, Rutkowski MR, Chopra S, Perales-Puchalt A, Song M, Zhang S, Bettigole SE, Gupta D, Holcomb K, Ellenson LH, Caputo T, Lee AH, Conejo-Garcia JR, Glimcher LH. ER Stress Sensor XBP1 Controls Anti-tumor Immunity by Disrupting Dendritic Cell Homeostasis. Cell 2015; 161:1527-38. PubMed
  • Chen X, Iliopoulos D, Zhang Q, Tang Q, Greenblatt MB, Hatziapostolou M, Lim E, Tam WL, Ni M, Chen Y, Mai J, Shen H, Hu DZ, Adoro S, Hu B, Song M, Tan C, Landis MD, Ferrari M, Shin SJ, Brown M, Chang JC, Liu XS, Glimcher LH. XBP1 promotes triple-negative breast cancer by controlling the HIF1α pathway. Nature 2014; 508:103-7. PubMed
  • Shim JH, Greenblatt MB, Zou W, Huang Z, Wein MN, Brady N, Hu D, Charron J, Brodkin HR, Petsko GA, Zaller D, Zhai B, Gygi S, Glimcher LH, Jones DC. Schnurri-3 regulates ERK downstream of WNT signaling in osteoblasts. J Clin Invest 2013; 123:4010-22. PubMed
  • Hetz C, Glimcher LH. Protein homeostasis networks in physiology and disease. Curr Opin Cell Biol 2011. PubMed
  • Glimcher LH, Martinon F, Modlin RL. Editorial overview. Curr Opin Immunol 2011; 23:1-2. PubMed
  • Zou W, Chen X, Shim JH, Huang Z, Brady N, Hu D, Drapp R, Sigrist K, Glimcher LH, Jones D. The E3 ubiquitin ligase Wwp2 regulates craniofacial development through mono-ubiquitylation of Goosecoid. Nat Cell Biol 2010; 13:59-65. PubMed
  • Lazarevic V, Chen X, Shim JH, Hwang ES, Jang E, Bolm AN, Oukka M, Kuchroo VK, Glimcher LH. T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the gene encoding ROR粒t. Nat Immunol 2010; 12:96-104. PubMed
  • Huh WJ, Esen E, Geahlen JH, Bredemeyer AJ, Lee AH, Shi G, Konieczny SF, Glimcher LH, Mills JC. XBP1 Controls Maturation of Gastric Zymogenic Cells by Induction of MIST1 and Expansion of the Rough Endoplasmic Reticulum. Gastroenterology 2010; 139:2038-49. PubMed
  • Collins PL, Chang S, Henderson M, Soutto M, Davis GM, McLoed AG, Townsend MJ, Glimcher LH, Mortlock DP, Aune TM. Distal regions of the human IFNG locus direct cell type-specific expression. J Immunol 2010; 185:1492-501. PubMed
  • Greenblatt MB, Shim JH, Zou W, Sitara D, Schweitzer M, Hu D, Lotinun S, Sano Y, Baron R, Park JM, Arthur S, Xie M, Schneider MD, Zhai B, Gygi S, Davis R, Glimcher LH. The p38 MAPK pathway is essential for skeletogenesis and bone homeostasis in mice. J Clin Invest 2010; 120:2457-73. PubMed
  • Martinon F, Chen X, Lee AH, Glimcher LH. TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages. Nat Immunol 2010; 11:411-8. PubMed
  • Garrett WS, Gordon JI, Glimcher LH. Homeostasis and Inflammation in the Intestine. Cell 2010; 140:859-870. PubMed
  • Anderson AC, Lord GM, Dardalhon V, Lee DH, Sabatos-Peyton CA, Glimcher LH, Kuchroo VK. T-bet, a Th1 transcription factor regulates the expression of Tim-3. Eur J Immunol 2010; 40:859-66. PubMed
  • Fathman JW, Gurish MF, Hemmers S, Bonham K, Friend DS, Grusby MJ, Glimcher LH, Mowen KA. NIP45 controls the magnitude of the type 2 T helper cell response. Proc Natl Acad Sci U S A 2010; 107:3663-8. PubMed
  • Riol-Blanco L, Lazarevic V, Awasthi A, Mitsdoerffer M, Wilson BS, Croxford A, Waisman A, Kuchroo VK, Glimcher LH, Oukka M. IL-23 receptor regulates unconventional IL-17-producing T cells that control bacterial infections. J Immunol 2010; 184:1710-20. PubMed
  • Jones DC, Glimcher LH. Regulation of bone formation and immune cell development by schnurri proteins. Adv Exp Med Biol 2009; 658:117-22. PubMed
  • Aliprantis AO, Glimcher LH. NFATc1 in Inflammatory and Musculoskeletal Conditions. Adv Exp Med Biol 2009; 658:69-75. PubMed
  • Matus S, Nassif M, Glimcher LH, Hetz C. XBP-1 deficiency in the nervous system reveals a homeostatic switch to activate autophagy. Autophagy 2009; 5:1226-8. PubMed
  • Jenner RG, Townsend MJ, Jackson I, Sun K, Bouwman RD, Young RA, Glimcher LH, Lord GM. The transcription factors T-bet and GATA-3 control alternative pathways of T-cell differentiation through a shared set of target genes. Proc Natl Acad Sci U S A 2009; 106:17876-81. PubMed
  • Hetz C, Thielen P, Matus S, Nassif M, Court F, Kiffin R, Martinez G, Cuervo AM, Brown RH, Glimcher LH. XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy. Genes Dev 2009; 23:2294-306. PubMed
  • Glimcher LH. Reflections on health care. J Clin Invest 2010; 119:2858-9. PubMed
  • Todd DJ, McHeyzer-Williams LJ, Kowal C, Lee AH, Volpe BT, Diamond B, McHeyzer-Williams MG, Glimcher LH. XBP1 governs late events in plasma cell differentiation and is not required for antigen-specific memory B cell development. J Exp Med 2009; 206:2151-9. PubMed
  • Hetz C, Glimcher LH. Fine-tuning of the unfolded protein response: Assembling the IRE1alpha interactome. Mol Cell 2009; 35:551-61. PubMed
  • Garrett WS, Punit S, Gallini CA, Michaud M, Zhang D, Sigrist KS, Lord GM, Glickman JN, Glimcher LH. Colitis-associated colorectal cancer driven by T-bet deficiency in dendritic cells. Cancer Cell 2009; 16:208-19. PubMed
  • Glimcher LH, Lee AH. From sugar to fat: How the transcription factor XBP1 regulates hepatic lipogenesis. Ann N Y Acad Sci 2009; 1173 Suppl 1:E2-9. PubMed
  • Shim JH, Greenblatt MB, Xie M, Schneider MD, Zou W, Zhai B, Gygi S, Glimcher LH. TAK1 is an essential regulator of BMP signalling in cartilage. EMBO J 2009; 28:2028-41. PubMed
  • Esensten JH, Lee MR, Glimcher LH, Bluestone JA. T-bet-deficient NOD mice are protected from diabetes due to defects in both T cell and innate immune system function. J Immunol 2009; 183:75-82. PubMed
  • Yuan X, Ansari MJ, D'Addio F, Paez-Cortez J, Schmitt I, Donnarumma M, Boenisch O, Zhao X, Popoola J, Clarkson MR, Yagita H, Akiba H, Freeman GJ, Iacomini J, Turka LA, Glimcher LH, Sayegh MH. Targeting Tim-1 to overcome resistance to transplantation tolerance mediated by CD8 T17 cells. Proc Natl Acad Sci U S A 2009; 106:10734-9. PubMed
  • Maldonado RA,Soriano MA,Perdomo LC,Sigrist K,Irvine DJ,Decker T,Glimcher LH. Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse. J Exp Med 2009; 206:877-92. PubMed
  • Lisbona F,Rojas-Rivera D,Thielen P,Zamorano S,Todd D,Martinon F,Glavic A,Kress C,Lin JH,Walter P,Reed JC,Glimcher LH,Hetz C. BAX inhibitor-1 is a negative regulator of the ER stress sensor IRE1alpha. Mol Cell 2009; 33:679-91. PubMed
  • Lazarevic V,Zullo AJ,Schweitzer MN,Staton TL,Gallo EM,Crabtree GR,Glimcher LH. The gene encoding early growth response 2, a target of the transcription factor NFAT, is required for the development and maturation of natural killer T cells. Nat Immunol 2009; 10:306-13. PubMed
  • Park JW,Min HJ,Sohn JH,Kim JY,Hong JH,Sigrist KS,Glimcher LH,Hwang ES. Restoration of T-box-containing protein expressed in T cells protects against allergen-induced asthma. J Allergy Clin Immunol 2008; 123:479-85. PubMed
  • Yuan X,Paez-Cortez J,Schmitt-Knosalla I,D'Addio F,Mfarrej B,Donnarumma M,Habicht A,Clarkson MR,Iacomini J,Glimcher LH,Sayegh MH,Ansari MJ. A novel role of CD4 Th17 cells in mediating cardiac allograft rejection and vasculopathy. J Exp Med 2008; 205:3133-44. PubMed
  • Wu J,Glimcher LH,Aliprantis AO. HCO3-/Cl- anion exchanger SLC4A2 is required for proper osteoclast differentiation and function. Proc Natl Acad Sci U S A 2008; 105:16934-9. PubMed
  • Aliprantis AO,Ueki Y,Sulyanto R,Park A,Sigrist KS,Sharma SM,Ostrowski MC,Olsen BR,Glimcher LH. NFATc1 in mice represses osteoprotegerin during osteoclastogenesis and dissociates systemic osteopenia from inflammation in cherubism. J Clin Invest 2008; 118:3775-89. PubMed
  • Kaser A,Lee AH,Franke A,Glickman JN,Zeissig S,Tilg H,Nieuwenhuis EE,Higgins DE,Schreiber S,Glimcher LH,Blumberg RS. XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 2008; 134:743-56. PubMed
  • Todd DJ,Lee AH,Glimcher LH. The endoplasmic reticulum stress response in immunity and autoimmunity. Nat Rev Immunol 2008; 8:663-74. PubMed
  • Werneck MB,Lugo-Villarino G,Hwang ES,Cantor H,Glimcher LH. T-bet plays a key role in NK-mediated control of melanoma metastatic disease. J Immunol 2008; 180:8004-10. PubMed
  • Tzianabos AO,Holsti MA,Zheng XX,Stucchi AF,Kuchroo VK,Strom TB,Glimcher LH,Cruikshank WW. Functional Th1 cells are required for surgical adhesion formation in a murine model. J Immunol 2008; 180:6970-6. PubMed
  • Mukherjee S, Raje N, Schoonmaker JA, Liu JC, Hideshima T, Wein MN, Jones DC, Vallet S, Bouxsein ML, Pozzi S, Chhetri S, Seo YD, Aronson JP, Patel C, Fulciniti M, Purton LE, Glimcher LH, Lian JB, Stein G, Anderson KC, Scadden DT. Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice. J Clin Invest 2008; 118:491-504. PubMed
  • Erlebacher A, Vencato D, Price KA, Zhang D, Glimcher LH. Constraints in antigen presentation severely restrict T cell recognition of the allogeneic fetus. J Clin Invest 2007; 117:1399-411. PubMed
  • Aliprantis AO, Wang J, Fathman JW, Lemaire R, Dorfman DM, Lafyatis R, Glimcher LH. Transcription factor T-bet regulates skin sclerosis through its function in innate immunity and via IL-13. Proc Natl Acad Sci U S A 2007; 104:2827-30. PubMed
  • Alcaide P, Jones TG, Lord GM, Glimcher LH, Hallgren J, Arinobu Y, Akashi K, Paterson AM, Gurish MA, Luscinskas FW. Dendritic cell expression of the transcription factor T-bet regulates mast cell progenitor homing to mucosal tissue. J Exp Med 2007; 204:431-9. PubMed
  • Taqueti VR, Grabie N, Colvin R, Pang H, Jarolim P, Luster AD, Glimcher LH, Lichtman AH. T-bet controls pathogenicity of CTLs in the heart by separable effects on migration and effector activity. J Immunol 2006; 177:5890-901. PubMed
  • Rosas LE, Snider HM, Barbi J, Satoskar AA, Lugo-Villarino G, Keiser T, Papenfuss T, Durbin JE, Radzioch D, Glimcher LH, Satoskar AR. Cutting Edge: STAT1 and T-bet play distinct roles in determining outcome of visceral leishmaniasis caused by Leishmania donovani. J Immunol 2006; 177:22-5. PubMed
  • Jones DC, Wein MN, Oukka M, Hofstaetter JG, Glimcher MJ, Glimcher LH. Regulation of adult bone mass by the zinc finger adapter protein Schnurri-3. Science 2006; 312:1223-7. PubMed
  • Shinohara ML, Lu L, Bu J, Werneck MB, Kobayashi KS, Glimcher LH, Cantor H. Osteopontin expression is essential for interferon-alpha production by plasmacytoid dendritic cells. Nat Immunol 2006; 7:498-506. PubMed
  • Hetz C, Bernasconi P, Fisher J, Lee AH, Bassik MC, Antonsson B, Brandt GS, Iwakoshi NN, Schinzel A, Glimcher LH, Korsmeyer SJ. Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha. Science 2006; 312:572-6. PubMed
  • Wang J, Fathman JW, Lugo-Villarino G, Scimone L, von Andrian U, Dorfman DM, Glimcher LH. Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells. J Clin Invest 2006; 116:414-21. PubMed
  • Garrett WS, Glimcher LH. T-bet-/- RAG2-/- ulcerative colitis: the role of T-bet as a peacekeeper of host-commensal relationships. Cytokine 2009; 48:144-7. PubMed
Hide