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Laurie Glimcher

Adjunct Professor of Immunology and Infectious Diseases

Department of Immunology and Infectious Diseases

Affiliations

Professor of Medicine, Harvard Medical School 
Senior Rheumatologist, Brigham and Women’s Hospital
Associate Member, Broad Institute
Team Leader, Ragon Institute of MGH, MIT and Harvard

Research

Laurie H. Glimcher, M.D. is the Irene Heinz Given Professor of Immunology at the Harvard School of Public Health, and Professor of Medicine at Harvard Medical School. She received her B.A. degree from Radcliffe College and her M.D. from Harvard Medical School. She received her postdoctoral training at Harvard and in the Laboratory of Immunology at the Institute of Allergy and Infectious Diseases in Bethesda. She is board certified in Internal Medicine and Rheumatology, and is a Senior Rheumatologist at the Brigham and Woman’s Hospital. She heads the Immunology Program at Harvard Medical School and the Division of Biological Sciences program at the Harvard School of Public Health. Dr. Glimcher received the Soma Weiss Award for Undergraduate Research, the Distinguished Young Investigator Award from the American College of Rheumatology, the Leukemia Society’s Stohlman Memorial Scholar Award, the Arthritis Foundation’s Lee S. Howley Award, the FASEB Excellence in Science Award, the American Society of Clinical Investigation Investigator Award, the Klemperer Award, the AAUW Senior Scholar award, the Huang Meritorious Career Award, and the American College of Rheumatology Distinguished Investigator Award.

She is a Fellow of the American Academy of Arts and Sciences, a Member of the Institute of Medicine of the National Academy of Sciences and a Member of the National Academy of Sciences. She is the former President of the American Association of Immunologists. Dr. Glimcher is a member of the American Asthma Foundation, Immune Diseases Institute, Health Care Ventures, Burroughs-Wellcome Fund and Memorial Sloan Kettering Cancer Center Scientific Advisory Boards and serves on the Cancer Research Institute Fellowship Committee. She is on the Corporate Board of Directors of the Bristol-Myers Squibb Pharmaceutical Corporation and the Waters Corporation.

Her laboratory uses biochemical and genetic approaches to elucidate the molecular pathways that regulate CD4 T helper cell development and activation. The complex regulatory pathways governing T helper cell responses are critical for both the development of protective immunity and for the pathophysiologic immune responses underlying autoimmune diseases. Her laboratory has studied the transcriptional pathways that control this important immune checkpoint. The Glimcher laboratory defined the genetic bases of both IL-4 and IFNg expression in T cells. They identified the proto-oncogene c-maf as the transcription factor responsible for Th2-specific IL-4 expression. Subsequently, her lab discovered the first Th1-specific transcription factor, T-bet and demonstrated that this single factor is a master-regulator of IFNg gene expression and the Th1 phenotype.

Recent studies have demonstrated that T-bet controls Type 1 immunity in cells of both the adaptive and innate immune system. The Glimcher laboratory has recently focused on the function of T-bet in dendritic cells in mucosal immunity and tumorigenesis with an emphasis on inflammatory bowel disease. They have expanded their interest in lineage commitment in lymphocytes to the B cell with the discovery of a transcription factor, XBP-1, that controls plasma cell differentiation and the Endoplasmic Reticulum (ER) Stress Response. They have provided evidence for a link between ER stress and proinflammatory/autoimmune, metabolic and neurodegenerative diseases. Skeletal biology is a separate interest of the laboratory arising from her lab’s discovery of a novel protein Schnurri-3 that controls adult bone formation. Large scale screens have identified new proteins that control osteoblast and osteoclast commitment and activation in skeletal biology.

Education

B.A., 1972, Harvard University
M.D., 1976, Harvard Medical School

Publications

Ho I-C, Hodge MR, Rooney JW, Glimcher LH. 1996. The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4. Cell 85:973-83.

Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman GC, Glimcher LH. 2000. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100:655-69.

Reimold AM, Iwakoshi NN, Manis J, Vallabhajosyula P, Szomolanyi-Tsuda E, Gravallese EM, Friend D, Grusby MJ, Alt F, Glimcher LH. 2001. Plasma cell differentiation requires transcription factor XBP-1. Nature 412:300-7.

Szabo SJ, Sullivan BM, Stemmann C, Satoskar AR, Sleckman BP, Glimcher LH. 2002. Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. Science 295:338-42.

Finotto S, Neurath MF, Glickman JN, Qin S, Lehr HA, Green FH, Ackerman K, Haley K, Galle PR, Szabo SJ, Drazen JM, De Sanctis GT, Glimcher LH. 2002. Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science 295:336-8.

Maldonado RA, Irvine DJ, Schreiber R, Glimcher LH. 2004. A role for the immunological synapse in lineage commitment of CD4 lymphocytes. Nature 431:527-32. 

Hwang ES, Szabo SJ, Schwartzberg PL, Glimcher LH. 2005. T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science 307:430-3.

Wang J, Fathman JW, Lugo-Villarino G, von Andrian U, Dorfman DM, Glimcher LH. 2006. Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells. J Clin Invest 16(2):414-21.

Jones DC, Wein MN, Oukka M, Hofstaetter JG, Glimcher MJ, Glimcher LH. 2006. Regulation of adult bone mass by the zinc finger adapter protein Schnurri-3. Science 312(5777):1223-7.

Garrett W, Lord GM, Punit S, Lugo G, Mazmanian S, Ito S, Glickman J, Glimcher LH. 2007. Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell 131:33-45. 

Lee Ah, Scapa EF, Cohen DE, Glimcher LH. 2008. Regulation of hepatic lipogenesis by the transcription factor XBP1. Science 320(5882):1492-6.

Kaser A, Lee AH, Franke A, Glickman JN, Zeissig S, Tilg H, Nieuwenhuis EES, Higgins DE, Schreiber S, Glimcher LH, Blumberg RS.  2008. Transcription factor XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 134:743-56.

Garrett W, Punit S, Gallini C, Michaud M, Zhang D, Sigrist K, Lord G, Glickman J, Glimcher LH. 2009. Colitis-associated colorectal cancer driven by T-bet deficiency in dendritic cells. Cancer Cell 16(3):208-19.

Hetz C, Thielen P, Matus S, Nassif M, Court F, María Cuervo AM, Martinez G, Kiffin R, Brown R, Glimcher LH. 2009. XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy. Genes Dev 23(19):2294-306. PMCID: 2758741.

Garrett WS, Gordon J, Glimcher LH. 2010. Homeostasis and inflammation in the Intestine. Cell 140(6):859-70.

Greenblatt MB, Shim JH, Zou W, Sitara D, Schweitzer M, Hu D, Lotinun S, Sano Y, Baron R, Park JM, Simon A, Xie M, Schneider MD, Zhai B, Gygi S, Davis R, Glimcher LH. 2010. A p 38 MAPK pathway essential for bone homeostasis. J Clin Invest 120(7):2457-73.

Garrett WS, Gallini CA, Yatsunenko T, Michaud M, DuBois A, Delaney ML, Punit S, Karlsson M, Bry L, Glickman JN, Gordon JI, Onderdonk AB, Glimcher LH. 2010. Enterobacteriaceae act in concert with a gut microbiota to induce both spontaneous and maternally-transmitted colitis. Cell Host Microbe (in press).