Photo of Stephanie K. Dougan,  PhD

Stephanie K. Dougan, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute


stephanie_dougan@dfci.harvard.edu

Stephanie K. Dougan, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Assistant Professor, Microbiology and Immunobiology, Harvard Medical School
  • Investigator, Cancer Immunology & Aids, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

The immune system is a powerful untapped resource for fighting tumors. Cytotoxic T cells can distinguish tumor cells from normal tissue with pinpoint precision, and they can locate and destroy tumor cells wherever they arise. Immune regulatory mechanisms impinge upon this idealized picture: tumors are notoriously adept at evading or usurping the endogenous anti-tumor immune response. Still, therapeutic interventions can reverse regulatory suppression, and so halt tumor progression or elicit regression. My long term goal is to understand the complex network of cellular interactions that shape the tumor microenvironment, and to develop novel therapeutics aimed at manipulating these dynamics. CD8 T cells do not occur in isolation; they operate in oligoclonal fashion amid regulatory T cells, myeloid cells and other immune infiltrates, not to mention heterogeneous tumor cells, stroma and vasculature. These interactions cannot be accurately modeled using xenografts, nor are they fully replicated in humanized mice that develop human leukocytes, but still face cross-species barriers with respect to immune-stromal interactions and T cell development. My lab clones mice from a variety of tumor-infiltrating lymphocytes in order to study the effects of each lymphocyte type in isolation, and more importantly, when combined with each other and with various immune-based therapies. We also use the technology in reverse to clone mice from tumor-infiltrating Tregs as a means of determining their antigen-specificity, with the ultimate goal of developing small molecule inhibitors for decreasing Treg accumulation in tumors.

 

Publications

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  • Maruyama T, Dougan SK, Truttmann MC, Bilate AM, Ingram JR, Ploegh HL. Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining. Nat Biotechnol 2015. PubMed
  • Huang YH, Zhu C, Kondo Y, Anderson AC, Gandhi A, Russell A, Dougan SK, Petersen BS, Melum E, Pertel T, Clayton KL, Raab M, Chen Q, Beauchemin N, Yazaki PJ, Pyzik M, Ostrowski MA, Glickman JN, Rudd CE, Ploegh HL, Franke A, Petsko GA, Kuchroo VK, Blumberg RS. CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Nature 2015; 517:386-90. 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
  • Dougan SK, Dougan M, Kim J, Turner JA, Ogata S, Cho HI, Jaenisch R, Celis E, Ploegh HL. Transnuclear TRP1-specific CD8 T cells with high or low affinity TCRs show equivalent antitumor activity. Cancer Immunol Res 2014; 1:99-111. PubMed
  • Dougan SK, Ogata S, Hu CC, Grotenbreg GM, Guillen E, Jaenisch R, Ploegh HL. IgG1+ ovalbumin-specific B-cell transnuclear mice show class switch recombination in rare allelically included B cells. Proc Natl Acad Sci U S A 2012; 109:13739-44. PubMed
  • Zeissig S, Dougan SK, Barral DC, Junker Y, Chen Z, Kaser A, Ho M, Mandel H, McIntyre A, Kennedy SM, Painter GF, Veerapen N, Besra GS, Cerundolo V, Yue S, Beladi S, Behar SM, Chen X, Gumperz JE, Breckpot K, Raper A, Baer A, Exley MA, Hegele RA, Cuchel M, Rader DJ, Davidson NO, Blumberg RS. Primary deficiency of microsomal triglyceride transfer protein in human abetalipoproteinemia is associated with loss of CD1 function. J Clin Invest 2010; 120:2889-99. PubMed
  • Hu CC, Dougan SK, Winter SV, Paton AW, Paton JC, Ploegh HL. Subtilase cytotoxin cleaves newly synthesized BiP and blocks antibody secretion in B lymphocytes. J Exp Med 2009; 206:2429-40. PubMed
  • McGehee AM, Dougan SK, Klemm EJ, Shui G, Park B, Kim YM, Watson N, Wenk MR, Ploegh HL, Hu CC. XBP-1-deficient plasmablasts show normal protein folding but altered glycosylation and lipid synthesis. J Immunol 2009; 183:3690-9. PubMed
  • Hu CC, Dougan SK, McGehee AM, Love JC, Ploegh HL. XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells. EMBO J 2009; 28:1624-36. PubMed
  • Dougan SK, Rava P, Hussain MM, Blumberg RS. MTP regulated by an alternate promoter is essential for NKT cell development. J Exp Med 2007; 204:533-45. PubMed
  • Dougan SK, Salas A, Rava P, Agyemang A, Kaser A, Morrison J, Khurana A, Kronenberg M, Johnson C, Exley M, Hussain MM, Blumberg RS. Microsomal triglyceride transfer protein lipidation and control of CD1d on antigen-presenting cells. J Exp Med 2005; 202:529-39. PubMed