DF/HCC Program Affiliation

Cancer Immunology

Research Abstract

LAURIE H. GLIMCHER, M.D., Irene Heinz Given Professor of Immunology (Harvard School of Public Health) and Professor of Medicine (HMS). The major focus of Dr. Glimcher's laboratory is the study of T helper cell differentiation. There is abundant evidence now that the ratio of Th1 to Th2 cells is highly relevant to clinical diseases, including autoimmune, infectious, and allergic diseases. Therefore, the ability to alter the ratios of Th1 and Th2 subsets provides exciting therapeutic options. Her laboratory has concentrated its efforts over the last year on ways in which this manipulation can be achieved. They recently demonstrated that costimulatory molecules can differentially drive T helper cell development Another approach to altering Th subset ratios is to increase or block the synthesis of or effects of selected cytokines. Dr. Glimcher's laboratory studies both the function of interleukin-4 by defining novel IL-4 inducible genes in T lymphocytes and the mechanisms that underlie tissue-specific cytokine gene transcription. Her laboratory has recently defined the genetic basis of IL-4 expression in T cells. Her group identified the proto-oncogene c-maf as the transcription factor responsible for Th2 specific IL-4 expression and subsequently isolated a second novel nuclear protein, NIP45, which together with c-maf and NF-AT allows reconstitution of IL-4 transcription in non-T cells. Her laboratory has also recently produced and characterized mice deficient in cytokine-specific transcription factors. Such mice have provided insight into the differential control of cytokine gene expression and have provided powerful models of allergic and autoimmune disease.

Publications

• 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 Feb 19;204
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• 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 May;7(5):498-506.
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• Shinohara ML, Jansson M, Hwang ES, Werneck MB, Glimcher LH, Cantor H.T-bet-dependent expression of osteopontin contributes to T cell polarization.Proc Natl Acad Sci U S A 2005 Nov 14.
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• Ranger AM, Oukka M, Rengarajan J, Glimcher LH.Inhibitory function of two NFAT family members in lymphoid homeostasis and Th2 development.Immunity 1998 Nov;9(5):627-35.
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• Ho IC, Hodge MR, Rooney JW, Glimcher LH.The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4.Cell 1996 Jun 28;85(7):973-83.
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