Cantrell, Doreen

Professor

1982 …2022

Research output per year

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Personal profile

Research

Analysis of signal transduction pathways that control T lymphocyte metabolism, migration and differentiation

The laboratory explores how antigen receptors and cytokines control the development and immune activation of T lymphocytes; key cells in the adaptive immune system.  The strategy is to rigorously interrogate T cell biology at the fundamental level of biochemical signal transduction.  The integration of mouse molecular genetics, cell biology and microscopy is then used to define the contribution of a particular biochemical pathway to T cell activation.  This work has defined how thymocytes and T lymphocytes use networks of guanine nucleotide binding proteins and serine kinases to interpret information from antigens and cytokines to make appropriate responses that control T cell development and peripheral T cell function.  The laboratory has made considerable progress mapping serine/threonine kinase mediated signaling pathways in thymocytes and peripheral T cells and has identified essential regulators of T cell metabolism, cytotoxic T cell effector function and CD8 T cell migration/trafficking.

The future research program will adopt a multidisciplinary approach and combine biochemistry, cell biology and in vivo mouse immunology to explore the how protein phosphorylation controls T cell function.   A key focus is the regulation of the metabolism of normal and malignant lymphocytes.  One important component of the work is a discovery based program to use high resolution mass spectrometry to systematically define the phosphoproteome of naïve and effector CD4 and CD8 T lymphocyte subpopulations. Phosphoproteomic analysis of cytotoxic T cells has already identified links between serine/threonine kinases and chromatin regulators; the future program will address how phosphorylation of these chromatin regulators controls CTL transcriptional programs and explore the role of key cytokines on the CD8 T cell phosphoproteome.  This work will generate a molecular understanding of how signal transduction pathways control T cell function.  In particular, the studies will provide new insights about pharmacological strategies that might manipulate immune responses to ensure effective vaccination and/or restrain the T cell pathology caused by effector T cells.

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Projects

Research Output

Open Access
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  • 12 Downloads (Pure)

    Antigen receptor control of methionine metabolism in T cells

    Sinclair, L. V., Howden, A., Brenes Murillo, A., Spinelli, L., Hukelmann, J., Macintyre, A. N., Liu, X., Thomson, S., Taylor, P., Rathmell, J. C., Locasale, J. W., Lamond, A. & Cantrell, D. A., 27 Mar 2019, In : eLife. 8, p. 1-29 29 p., e44210.

    Research output: Contribution to journalArticle

    Open Access
    File
  • 11 Citations (Scopus)
    95 Downloads (Pure)

    Move to metabolism

    Cantrell, D. A., 29 Mar 2019, In : Nature Reviews Immunology. 19, 1 p., 270.

    Research output: Contribution to journalComment/debate

  • Phenformin, but not metformin, delays development of T-cell acute lymphoblastic leukemia/lymphoma via cell-autonomous AMPK activation

    Vara Ciruelos, D., Dandapani, M., Russell, F., Grzes, K. M., Atrih, A., Foretz, M., Viollet, B., Lamont, D., Cantrell, D. & Hardie, G., 16 Apr 2019, In : Cell Reports. 27, 3, p. 690-698.e4

    Research output: Contribution to journalArticle

    Open Access
    File
  • 7 Citations (Scopus)
    101 Downloads (Pure)
  • 3 Citations (Scopus)

    Activities

    • 1 Festival/Exhibition
    • 1 Public engagement and outreach - festival/exhibition

    Inspiring Stories from Women in STEM Storytelling Night

    Heather Doran (Organiser), Amy Cameron (Organiser), Amy Rogers (Speaker), Lucina Hackman (Speaker), Zoe McElhinney (Speaker), Caroline Hall (Speaker), Laura Daly (Speaker), Doreen Cantrell (Speaker)
    11 Mar 2019

    Activity: Other activity typesPublic engagement and outreach - festival/exhibition

    Local inspirations for the Scientific Life

    Doreen Cantrell (Speaker)
    19 Mar 2014

    Activity: Participating in or organising an event typesFestival/Exhibition

    Thesis

    Environmental signals that control T lymphocytes in the gastrointestinal tract

    Author: Ramsay, G., 2015

    Supervisor: Cantrell, D. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy

    Exploring the role and the function of Aryl Hydrocarbon Receptor (AhR) and Aryl Hydrocarbon Nuclear Translocator (ARNT) in T cells

    Author: Rosenzweig, E., 2012

    Supervisor: Cantrell, D. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy

    File

    Metabolic regulation in Phosphatase and tensin homologue (PTEN) null T cell lymphoma/leukaemia cells

    Author: Grzes, K. M., 2015

    Supervisor: Cantrell, D. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy

    File

    Regulation of Protein Kinase D

    Author: Matthews, S., 2000

    Supervisor: Cantrell, D. (Supervisor) & Rozengurt, E. (External person) (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy

    The role of JAK1 and JAK3 in CD8+ effector T cells

    Author: Rollings, C., 2016

    Supervisor: Cantrell, D. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy

    File