• Researcher Profile

    Stephanie K. Dougan, PhD

     
    Stephanie K. Dougan, PhD
     
    Assistant Professor

    Office phone: 617-582-9609
    Email: stephanie_dougan@dfci.harvard.edu
    Website: Dept of Cancer Immunology & AIDs

    Preferred contact method: email
     
     

    Research Department

    Cancer Immunology and AIDS

    Area of Research

    Development of preclinical models for immunotherapy.

    Tumor immunology, Development of preclinical models for immunotherapy, transnuclear and CRISPR gene-modified mice, tumor infiltrating CD8 T cells and regulatory T cells, melanoma and pancreatic cancers.


    Dana-Farber Cancer Institute
    450 Brookline Avenue
    Smith 770A
    Boston, MA 02215

    Biography

    Stephanie Dougan received her PhD in immunology from Harvard University in 2007 after studying NKT cells and CD1d antigen presentation with Dr. Richard Blumberg. She then performed postdoctoral work at the Whitehead Institute with Dr. Hidde Ploegh. While at Whitehead, she collaborated with Dr. Rudolf Jaenisch to learn somatic cell nuclear transfer and generate a panel of transnuclear mice. Stephanie Dougan joined the DFCI and Harvard faculty in 2014.

    Recent Awards

    • Pathway to Leadership Award, Pancreatic Cancer Action Network and the American Association of Cancer Research, 2012-2017

    Research

    Development of preclinical models for immunotherapy.

    Tumor immunology, Development of preclinical models for immunotherapy, transnuclear and CRISPR gene-modified mice, tumor infiltrating CD8 T cells and regulatory T cells, melanoma and pancreatic cancers.

    Somatic cell nuclear transfer (SCNT) may be used to clone mice from lymphocytes of defined specificity. By harvesting as few as 200 primary lymphocytes from animals that are at the peak of an immune response, and by transfer of the nucleus from such antigen specific lymphocytes into an enucleated oocyte, embryonic stem cells that harbor the genetic rearrangements encoding the original antigen receptor may be obtained and used for the construction of transnuclear mice. These animals contain T or B cells of the appropriate specificity, have no genetic alterations other than the physiological TCR/BCR rearrangements and are the closest approximation of physiological immune responses to date. Importantly, the generation of transnuclear mice is rapid, requiring approximately 6 weeks from T cell harvest to obtaining chimeric animals. Like TCR and BCR transgenics, transnuclear mice are broadly useful for addressing diverse questions. The Dougan lab generates transnuclear mouse models to explore questions of anti-tumor immunity.

    Our long term goal is to understand the complex network of cellular interactions that shape the tumor microenvironment. 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. The Dougan 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.

    Currently the lab focuses on three major tumor types: melanoma, sarcoma and pancreatic cancer. Of these, pancreatic cancer has been the most refractory to immunotherapy. We are using a combination of RNAseq profiling and targeted gene silencing in pancreatic-tumor specific CD8 T cells to design effective immunotherapies for pancreatic cancer.

    Select Publications

    • Dougan SK, Hu CC, Paquet ME, Greenblatt MB, Kim J, Lilley BN, Watson N, Ploegh HL. Derlin-2 deficient mouse reveals an essential role for protein dislocation in chondrocytes. Mol Cell Biol. 2011; 31:1145-59.
    • 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.
    • Dougan SK, Ashour J, Karssemeijer RA, Popp MW, Avalos AM, Barisa M, Altenburg AF, Ingram JR, Cragnolini JJ, Guo C, Alt FW, Jaenisch R, Ploegh HL. Antigen-specific B cell receptor sensitizes B cells to infection and killing by influenza virus. Nature. 2013; 503:406-9.
    • 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 anti-tumor activity. Cancer Immunol Res. 2013; 1:99-111.
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