• Researcher Profile

    Shannon Turley, PhD

     
    Shannon Turley, PhD
     
    Associate Professor of Microbiology & Immunobiology, Harvard Medical School

    Office phone: 617-632-4990
    Fax: 617-582-7999
    Email: shannon_turley@dfci.harvard.edu

    Preferred contact method: appointment phone
     
     

    Research Department

    Cancer Immunology and AIDS

    Area of Research

    Initiation of Immune Responses by Dendritic Cells

    Dana-Farber Cancer Institute
    450 Brookline Avenue
    Dana 1440a
    Boston, MA 02215

    Biography

    Dr. Turley received her PhD in 1999 from Yale University, and later completed postdoctoral training in immunology at Joslin Diabetes Center in Boston. In 2004, she became assistant professor of pathology at Harvard Medical School and in the Department of Cancer Immunology at DFCI, where she works on the initiation of immune responses by dendritic cells.

    Research

    Initiation of Immune Responses by Dendritic Cells

    Our laboratory is interested in understanding the cellular and molecular basis of T cell priming by dendritic cells (DCs) in diseases such as type 1 diabetes and pancreatic cancer.

    Adaptive immune responses begin with the stimulation of naive T cells and the subsequent generation of effector T cells, a process generically referred to as priming. T cells do not recognize antigens in their native state but rather respond to MHC-peptide complexes on the plasma membrane of an antigen-presenting cell. Because naive T cells home to specific regions of secondary lymphoid organs that are impenetrable by most free antigens, epitopes for which they are specific must be delivered to T cell zones of secondary lymphoid tissues and presented there by professional antigen-presenting cells. DCs, the most potent of all antigen-presenting cells, are essential players at every step of this process.

    A major focus of our research is the impact of healthy and inflamed tissue microenvironments on the development, differentiation, and function of DCs. In particular, we strive to understand how perturbations to the tissue microenvironment affect the presentation of self-antigens by DCs. We combine transgenic mouse models and high-resolution imaging technologies to explore endocytosis, transport, and processing of tissue-restricted antigens by DCs. We recently developed two mouse models in which specific mutations in the NF-kappa B pathway and new variants of fluorescent proteins are targeted selectively to DCs. We have also initiated studies to discover novel genes that regulate the internalization and processing of self-antigens by DCs.

    Ultimately, elucidating the steps leading to primary immune responses against self-antigens should provide the necessary framework for enhancing this process in cancer and dampening it in autoimmune diseases.

    Select Publications

    • Turley SJ, Tan EM, Pollard KM. 1993. Molecular cloning and sequence analysis of U3 snoRNA-associated mouse fibrillarin. Biochim. Biophys. Acta. 1216:119-122.
    • Hultman P, Enestrom S, Turley SJ, Pollard KM. 1994. Selective induction of anti-fibrillarin autoantibodies by silver nitrate in mice. Clin. Exp. Immunol. 96:285-291.
    • Hultman P, Johansson U, Turley SJ, Lindh U, Enestrom S, Pollard KM. 1994. Adverse immunological effects and autoimmunity induced by dental amalgam and alloy in mice. FASEB. J. 8:1183-1190.
    • Hultman P, Ganowiak K, Turley SJ, Pollard KM. 1995. Genetic susceptibility to silver-induced anti-fibrillarin autoantibodies in mice. Clin. Immunol. Immunopathol. 77:291-297.
    • Takeuchi K, Turley SJ, Tan EM, Pollard KM. 1995. Analysis of the autoantibody resonse to fibrillarin in human disease and murine models of autoimmunity. J. Immunol. 154:961-971.
    • Hultman P, Turley SJ, Enestrom S, Lindh U, Pollard KM. 1996. Murine genotype influences the specificity, magnitude, and persistence of murine mercury-induced autoimmunity. J. Autoimmun. 9:139-149.
    • Pierre P, Turley SJ, Meltzer J, Mirze A, Steinman R, Mellman I. 1997. Localization and intracellular transport of MHC class II molecules in bone marrow-derived dendritic cells. Adv. Exp. Med. Biol. 417:179-182.
    • Sacca R, Turley S, Soong L, Mellman I, Ruddle N. 1997. Transgenic expression of lymphotoxin restores -deficient mice.lymph nodes to lymphotoxin- J. Immunol. 159:4252-4260.
    • Phase II prospective study of paclitaxel and carboplatin in older patients with newly diagnosed Mllerian tumors. Matulonis UA, Krag KJ, Krasner CN, Atkinson T, Horowitz NS, Lee H, Penson RT. Gynecol Oncol. 2009 Feb;112(2):394-9. Epub 2008 Dec 5.
    • Inaba K, Turley SJ, Yamaide F, Iyoda T, Pack M, Inaba M,. Mahnke K, Sauter B, Albert M, Subklewe M, Sheff D, Bhardwaj, N, Mellman I, Steinman RM. 1998. Efficient presentation of phagocytosed cellular fragments on MHC class II products of dendritic cells. J. Exp. Med. 188:2163-2173.
    • Talmor M, Mirza A, Turley S, Mellman I, Hoffman LA, Steinman RM. 1998. Generation of large numbers of immature and mature dendritic cells from rat bone marrow cultures. Eur. J. Immunol. 28:811-817.
    • Turley SJ, Inaba K, Garrett WS, Ebersold M, Unternaerher J, Steinman RM, Mellman I. 2000. Transport of peptide-MHC class II complexes in developing dendritic cells. Science. 288:522-527.
    • Inaba K, Turley SJ, Iyoda T, Yamaide F, Shimoyama S, Reis e Sousa C, Germain R. Mellman I, Steinman RM. 2000. The formation of immunogenic MHC class II-peptide ligands in lysosomal compartments of dendritic cells is regulated by inflammatory stimuli. J. Exp. Med. 191:927-936.
    • Garrett WS, Chen LM, Kroscheswski R, Ebersold M, Turley S, Trombetta S, Galan JE, Mellman I. 2000. Developmental control of endocytosis in dendritic cells by Cdc42. Cell. 102:325-334.
    • Yang J-M, Baserga SJ, Turley SJ, Pollard KM. 2001. Fibrillarin and other snoRNP proteins are targets of autoantibodies in xenobiotic-induced autoimmunity. Clin. Immunol. 101:38-50.
    • Anderson MS, Venanzi ES, Klein L, Chen Z, Berzins S, Turley SJ, von Boehmer H, Bronson R, Dierich A, Benoist C, Mathis D. 2002. Projection of an immunological self-shadow within the thymus by the aire protein. Science. 298:1395-401.
    • Turley S, Poirot L, Hattori M, Benoist C, Mathis D. 2003. Physiological -cell death triggers priming of self-reactive T cells by dendritic cells in a type-1 diabetes model. J Exp Med. 198:1527-37.
    • Lee LF, Xu B, Michie S, Turley S, McDevitt HO. 2005. The role of TNF in the pathogenesis of type-1 diabetes in the NOD mouse: Analysis of dendritic cell maturation. Proc. Nat. Acad. Sci. 102:15995-16000.
    • Turley SJ, Lee JW, Dutton-Swain N, Mathis D. Benoist C. 2005. Endocrine self and gut non-self intersect in pancreatic lymph nodes. Proc. Nat. Acad. Sci. 102: 17729-17733.
    • Lee JW, Epardaud M, Sun J, Becker JE, Cheng AC, Yonekura A, Heath JK, Turley SJ. 2007. Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self. Nat. Immunol. 8;2: 181-190.
    • Takeda Y, Kazarov AR, Epardaud M, Turley SJ, and Hemler ME. 2007. Diminished lung metastasis in tetraspanin CD151 knockout mice. Submitted.
    • Epardaud M, Rubinstein MP, Yonekura A, Bellemare-Pelletier A, Bronson R, Hamerman JA, Goldrath AW, and Turley SJ. 2008. IL-15/IL-15R complexes promote destruction of established tumors by reviving tumor-resident CD8+ T cells. Can Res. 68(8):2972-83.
    • Magnusson FC, Liblau RS, von Boehmer H, Pittet MJ, Lee JW, Turley SJ, and Khazaie K. 2008. Direct presentation of antigen protects against CD8 T-cell mediated intestinal autoimmunity. Gastroenterol. 134(4):1028-37.
    • Magnusson FC, Liblau RS, von Boehmer H, Turley SJ, Gounari F, and Khazaie K. 2008. CD8 T cell tolerance mediated by cross-presentation but not by direct presentation of antigen requires sensitivity of CD8 T cells to TGF signaling. Submitted.
    • Heng TS, Painter MW, Elpek K, Lukacs-Kornek V, Mauermann N, Turley SJ, Koller D, Kim FS, Wagers AJ, Asinovski N, Davis S, Fassett M, Feuerer M, Gray DH, Haxhinasto S, Hill JA, Hyatt G, Laplace C, Leatherbee K, Mathis D, Benoist C, Jianu R, Laidlaw DH, Best JA, Knell J, Goldrath AW, Jarjoura J, Sun JC, Zhu Y, Lanier LL, Ergun A, Li Z, Collins JJ, Shinton SA, Hardy RR, Friedline R, Sylvia K, Kang J. 2008. The Immunological Genome Project: networks of gene expression in immune cells. Nat Immunol. 9(10):1091-4.
    • Reynoso ED, Elpek KG, Francisco L, Bronson R, Bellemare-Pelletier A, Sharpe AH, Freeman GJ, and Turley SJ. 2008. Intestinal tolerance is converted to autoimmune enteritis upon PD-1 ligand blockade. J. Immunol. 182(4):2102-12.
    • Yip L, Su L, Sheng D, Chang P, Atkinson M, Czesak M, Albert PR, Collier AY, Turley SJ, Fathman CG, Creusot RJ. 2009. Deaf1 isoforms control changes in PTA gene expression in the PLN during T1D pathogenesis. Nat. Immunol. 10(9):1026-33.
    • Gardner JM, Fletcher AL, Anderson MS, Turley SJ. 2009. AIRE in the thymus and beyond. Curr. Opin. Immunol. 21(6):582-9.
    • Reynoso ED and Turley SJ. 2009. Unconventional antigen-presenting cells in the induction of peripheral CD8+ T cell tolerance. J. Leuk. Biol. 86(4): 795-801.
    • Reynoso ED, Lee JW, Turley SJ. 2009. Peripheral tolerance induction by lymph node stroma. Adv Exp Med Biol. 633:113-27.

    Trainees

    • Elpek, Kutlu, Ph.D.
    • Lukacs-Kornek, Veronika, Ph.D.
    • Fletcher, Anne, Ph.D.
    • Pinner, Sophie, Ph.D.
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