Photo of Shannon J. Turley,  PhD

Shannon J. Turley, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-4990
Fax: (617) 582-7999


shannon_turley@dfci.harvard.edu

Shannon J. Turley, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Associate Professor, Microbiology and Immunobiology, Harvard Medical School
  • Assistant Professor, Cancer Immunology/AIDS, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

We are interested in understanding the mechanisms by which dendritic cells provoke primary T cell responses in autoimmune diseases such as type-1 diabetes and celiac disease and in pancreatic cancer. We employ transgenic mouse models to decipher the molecular and cellular specializations of dendritic cells that allow these cells to capture, traffic, process and present antigens derived from healthy, developing, and injured tissues. In other studies, we utilize high resolution imaging technologies to investigate the trafficking of antigen and dendritic cells from non-lymphoid organs to draining lymph nodes. We are currently engineering transgenic models in which specific mutations can be targeted to dendritic cells in an inducible manner. Conditional gene targeting in dendritic cells will allow us to more precisely dissect the physiology and function of these critical antigen-presenting cells in health and disease. Elucidating the steps leading to nae T cell activation should provide the necessary framework for enhancing this process in cancer and dampening it in autoimmune diseases.

Publications

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  • Platzer B, Elpek KG, Cremasco V, Baker K, Stout MM, Schultz C, Dehlink E, Shade KT, Anthony RM, Blumberg RS, Turley SJ, Fiebiger E. IgE/Fc竜RI-Mediated Antigen Cross-Presentation by Dendritic Cells Enhances Anti-Tumor Immune Responses. Cell Rep 2015. PubMed
  • Chang JE, Turley SJ. Stromal infrastructure of the lymph node and coordination of immunity. Trends Immunol 2014; 36:30-9. PubMed
  • Yoda A, Adelmant G, Tamburini J, Chapuy B, Shindoh N, Yoda Y, Weigert O, Kopp N, Wu SC, Kim SS, Liu H, Tivey T, Christie AL, Elpek KG, Card J, Gritsman K, Gotlib J, Deininger MW, Makishima H, Turley SJ, Javidi-Sharifi N, Maciejewski JP, Jaiswal S, Ebert BL, Rodig SJ, Tyner JW, Marto JA, Weinstock DM, Lane AA. Mutations in G protein 硫 subunits promote transformation and kinase inhibitor resistance. Nat Med 2015; 21:71-5. PubMed
  • Elpek KG, Cremasco V, Shen H, Harvey CJ, Wucherpfennig KW, Goldstein DR, Monach PA, Turley SJ. The tumor microenvironment shapes lineage, transcriptional, and functional diversity of infiltrating myeloid cells. Cancer Immunol Res 2014. PubMed
  • Knoblich K, Wang HX, Sharma C, Fletcher AL, Turley SJ, Hemler ME. Tetraspanin TSPAN12 regulates tumor growth and metastasis and inhibits 硫-catenin degradation. Cell Mol Life Sci 2014; 71:1305-14. PubMed
  • Zhou P, Shaffer DR, Alvarez Arias DA, Nakazaki Y, Pos W, Torres AJ, Cremasco V, Dougan SK, Cowley GS, Elpek K, Brogdon J, Lamb J, Turley SJ, Ploegh HL, Root DE, Love JC, Dranoff G, Hacohen N, Cantor H, Wucherpfennig KW. In vivo discovery of immunotherapy targets in the tumour microenvironment. Nature 2014; 506:52-7. 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
  • Malhotra D, Fletcher AL, Turley SJ. Stromal and hematopoietic cells in secondary lymphoid organs: partners in immunity. Immunol Rev 2013; 251:160-76. 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
  • Miller JC, Brown BD, Shay T, Gautier EL, Jojic V, Cohain A, Pandey G, Leboeuf M, Elpek KG, Helft J, Hashimoto D, Chow A, Price J, Greter M, Bogunovic M, Bellemare-Pelletier A, Frenette PS, Randolph GJ, Turley SJ, Merad M, . Deciphering the transcriptional network of the dendritic cell lineage. Nat Immunol 2012; 13:888-99. PubMed
  • Acton SE, Astarita JL, Malhotra D, Lukacs-Kornek V, Franz B, Hess PR, Jakus Z, Kuligowski M, Fletcher AL, Elpek KG, Bellemare-Pelletier A, Sceats L, Reynoso ED, Gonzalez SF, Graham DB, Chang J, Peters A, Woodruff M, Kim YA, Swat W, Morita T, Kuchroo V, Carroll MC, Kahn ML, Wucherpfennig KW, Turley SJ. Podoplanin-rich stromal networks induce dendritic cell motility via activation of the C-type lectin receptor CLEC-2. Immunity 2012; 37:276-89. PubMed
  • Astarita JL, Acton SE, Turley SJ. Podoplanin: emerging functions in development, the immune system, and cancer. 2012; 3:283. PubMed
  • Lv H, Havari E, Pinto S, Gottumukkala RV, Cornivelli L, Raddassi K, Matsui T, Rosenzweig A, Bronson RT, Smith R, Fletcher AL, Turley SJ, Wucherpfennig K, Kyewski B, Lipes MA. Impaired thymic tolerance to 留-myosin directs autoimmunity to the heart in mice and humans. J Clin Invest 2011. PubMed
  • Lukacs-Kornek V, Turley SJ. Self-antigen presentation by dendritic cells and lymphoid stroma and its implications for autoimmunity. Curr Opin Immunol 2011; 23:138-45. PubMed
  • Fletcher AL, Malhotra D, Turley SJ. Lymph node stroma broaden the peripheral tolerance paradigm. Trends Immunol 2011; 32:12-8. PubMed
  • Elpek KG, Rubinstein MP, Bellemare-Pelletier A, Goldrath AW, Turley SJ. Mature natural killer cells with phenotypic and functional alterations accumulate upon sustained stimulation with IL-15/IL-15Ralpha complexes. Proc Natl Acad Sci U S A 2011; 107:21647-52. PubMed
  • Levy C, Khaled M, Iliopoulos D, Janas MM, Schubert S, Pinner S, Chen PH, Li S, Fletcher AL, Yokoyama S, Scott KL, Garraway LA, Song JS, Granter SR, Turley SJ, Fisher DE, Novina CD. Intronic miR-211 Assumes the Tumor Suppressive Function of Its Host Gene in Melanoma. Mol Cell 2010; 40:841-849. PubMed
  • Turley SJ, Fletcher AL, Elpek KG. The stromal and haematopoietic antigen-presenting cells that reside in secondary lymphoid organs. Nat Rev Immunol 2010; 10:813-25. PubMed
  • Gonzalez SF, Lukacs-Kornek V, Kuligowski MP, Pitcher LA, Degn SE, Turley SJ, Carroll MC. Complement-dependent transport of antigen into B cell follicles. J Immunol 2010; 185:2659-64. PubMed
  • Gonzalez SF, Lukacs-Kornek V, Kuligowski MP, Pitcher LA, Degn SE, Kim YA, Cloninger MJ, Martinez-Pomares L, Gordon S, Turley SJ, Carroll MC. Capture of influenza by medullary dendritic cells via SIGN-R1 is essential for humoral immunity in draining lymph nodes. Nat Immunol 2010; 11:427-34. PubMed
  • Fletcher AL, Lukacs-Kornek V, Reynoso ED, Pinner SE, Bellemare-Pelletier A, Curry MS, Collier AR, Boyd RL, Turley SJ. Lymph node fibroblastic reticular cells directly present peripheral tissue antigen under steady-state and inflammatory conditions. J Exp Med 2010; 207:689-97. PubMed
  • Gardner JM, Fletcher AL, Anderson MS, Turley SJ. AIRE in the thymus and beyond. Curr Opin Immunol 2009; 21:582-9. PubMed
  • Reynoso ED, Turley SJ. Unconventional antigen-presenting cells in the induction of peripheral CD8(+) T cell tolerance. J Leukoc Biol 2009; 86:795-801. PubMed
  • Reynoso ED,Elpek KG,Francisco L,Bronson R,Bellemare-Pelletier A,Sharpe AH,Freeman GJ,Turley SJ. Intestinal tolerance is converted to autoimmune enteritis upon PD-1 ligand blockade. J Immunol 2009; 182:2102-12. PubMed
  • Reynoso ED,Lee JW,Turley SJ. Peripheral tolerance induction by lymph node stroma. Adv Exp Med Biol 2009; 633:113-27. PubMed
  • Epardaud M, Elpek KG, Rubinstein MP, Yonekura AR, Bellemare-Pelletier A, Bronson R, Hamerman JA, Goldrath AW, Turley SJ. Interleukin-15/interleukin-15R alpha complexes promote destruction of established tumors by reviving tumor-resident CD8+ T cells. Cancer Res 2008; 68:2972-83. PubMed
  • Lee JW, Epardaud M, Sun J, Becker JE, Cheng AC, Yonekura AR, Heath JK, Turley SJ. Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self. Nat Immunol 2007; 8:181-90. PubMed
  • Turley SJ, Lee JW, Dutton-Swain N, Mathis D, Benoist C. Endocrine self and gut non-self intersect in the pancreatic lymph nodes. Proc Natl Acad Sci U S A 2005; 102:17729-33. PubMed
  • Lee LF, Xu B, Michie SA, Beilhack GF, Warganich T, Turley S, McDevitt HO. The role of TNF-{alpha} in the pathogenesis of type 1 diabetes in the nonobese diabetic mouse: Analysis of dendritic cell maturation. Proc Natl Acad Sci U S A 2005; 102:15995-6000. PubMed
  • Turley S, Poirot L, Hattori M, Benoist C, Mathis D. Physiological beta cell death triggers priming of self-reactive T cells by dendritic cells in a type-1 diabetes model. J Exp Med 2003; 198:1527-37. PubMed
  • Turley SJ. Dendritic cells: inciting and inhibiting autoimmunity. Curr Opin Immunol 2002; 14:765-70. PubMed
  • Anderson MS, Venanzi ES, Klein L, Chen Z, Berzins SP, Turley SJ, von Boehmer H, Bronson R, Dierich A, Benoist C, Mathis D. Projection of an immunological self shadow within the thymus by the aire protein. Science 2002; 298:1395-401. PubMed
  • Turley SJ, Inaba K, Garrett WS, Ebersold M, Unternaehrer J, Steinman RM, Mellman I. Transport of peptide-MHC class II complexes in developing dendritic cells. Science 2000; 288:522-7. PubMed
  • Inaba K, Turley S, Iyoda T, Yamaide F, Shimoyama S, Reis e Sousa C, Germain RN, Mellman I, Steinman RM. The formation of immunogenic major histocompatibility complex class II-peptide ligands in lysosomal compartments of dendritic cells is regulated by inflammatory stimuli. J Exp Med 2000; 191:927-36. PubMed
  • Steinman RM, Turley S, Mellman I, Inaba K. The induction of tolerance by dendritic cells that have captured apoptotic cells. J Exp Med 2000; 191:411-6. PubMed
  • Inaba K, Turley S, Yamaide F, Iyoda T, Mahnke K, Inaba M, Pack M, Subklewe M, Sauter B, Sheff D, Albert M, Bhardwaj N, Mellman I, Steinman RM. Efficient presentation of phagocytosed cellular fragments on the major histocompatibility complex class II products of dendritic cells. J Exp Med 1998; 188:2163-73. PubMed
  • Mellman I, Turley SJ, Steinman RM. Antigen processing for amateurs and professionals. Trends Cell Biol 1998; 8:231-7. PubMed
  • Talmor M, Mirza A, Turley S, Mellman I, Hoffman LA, Steinman RM. Generation or large numbers of immature and mature dendritic cells from rat bone marrow cultures. Eur J Immunol 1998; 28:811-7. PubMed
  • Sacca R, Turley S, Soong L, Mellman I, Ruddle NH. Transgenic expression of lymphotoxin restores lymph nodes to lymphotoxin-alpha-deficient mice. J Immunol 1997; 159:4252-60. PubMed
  • Pierre P, Turley SJ, Gatti E, Hull M, Meltzer J, Mirza A, Inaba K, Steinman RM, Mellman I. Developmental regulation of MHC class II transport in mouse dendritic cells. Nature 1997; 388:787-92. PubMed
  • Takeuchi K, Turley SJ, Tan EM, Pollard KM. Analysis of the autoantibody response to fibrillarin in human disease and murine models of autoimmunity. J Immunol 1995; 154:961-71. PubMed
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