University of Dundee

Professor Doreen Cantrell CBE FRS FRSE FMedSci

T-lymphocyte signal transduction
Professor of Cellular Immunology and Wellcome Trust Principal Research Fellow
School of Life Sciences, University of Dundee, Dundee
Full Telephone: 
+44 (0) 1382 385156, int ext 85156


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.


Rollings, C., Sinclair, L.V., Brady H.J.M., Cantrell, D. A. and Ross, S. H. (2018) Interleukin-2 shapes the cytotoxic T cell proteome and immune-environment sensing programs. Science Signaling. 11, eaap8112.
d.o.i 10.1126/scisignal.aap8112
Pubmed: 29666307
Ross, S. H., Rollings, C., Anderson, K. E., Hawkins, P. T., Stephens, L. R. and Cantrell, D. A. (2016) Phosphoproteomic Analyses of Interleukin 2 Signaling Reveal Integrated JAK Kinase-Dependent and -Independent Networks in CD8(+) T Cells. Immunity. 45, 685-700
d.o.i 10.1016/j.immuni.2016.07.022
Pubmed: 5040828
PMC: 27566939
Swamy, M., Pathak, S., Grzes, K. M., Damerow, S., Sinclair, L. V., van Aalten, D. M. and Cantrell, D. A. (2016) Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy. Nature immunology. 17, 712-720
d.o.i 10.1038/ni.3439
Pubmed: 4900450
PMC: 27111141
Hukelmann, J. L., Anderson, K. E., Sinclair, L. V., Grzes, K. M., Murillo, A. B., Hawkins, P. T., Stephens, L. R., Lamond, A. I. and Cantrell, D. A. (2016) The cytotoxic T cell proteome and its shaping by the kinase mTOR. Nature immunology. 17, 104-112
d.o.i 10.1038/ni.3314
Pubmed: 4685757
PMC: 26551880
Preston, G. C., Sinclair, L. V., Kaskar, A., Hukelmann, J. L., Navarro, M. N., Ferrero, I., MacDonald, H. R., Cowling, V. H. and Cantrell, D. A. (2015) Single cell tuning of Myc expression by antigen receptor signal strength and interleukin-2 in T lymphocytes. The EMBO journal. 34, 2008-2024
d.o.i 10.15252/embj.201490252
Pubmed: 4551349
PMC: 26136212
Navarro, M. N., Goebel, J., Hukelmann, J. L. and Cantrell, D. A. (2014) Quantitative phosphoproteomics of cytotoxic T cells to reveal protein kinase d 2 regulated networks. Molecular & cellular proteomics : MCP. 13, 3544-3557
d.o.i 10.1074/mcp.M113.037242
Pubmed: 4256504
PMC: 25266776
Navarro, M. N., Feijoo-Carnero, C., Arandilla, A. G., Trost, M. and Cantrell, D. A. (2014) Protein kinase D2 is a digital amplifier of T cell receptor-stimulated diacylglycerol signaling in naive CD8(+) T cells. Science signaling. 7, ra99
d.o.i 10.1126/scisignal.2005477
Pubmed: 4768351
PMC: 25336615
Sinclair, L. V., Rolf, J., Emslie, E., Shi, Y. B., Taylor, P. M. and Cantrell, D. A. (2013) Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation. Nature immunology. 14, 500-508
d.o.i 10.1038/ni.2556
Pubmed: 3672957
PMC: 23525088
Rolf, J., Zarrouk, M., Finlay, D. K., Foretz, M., Viollet, B. and Cantrell, D. A. (2013) AMPKalpha1: a glucose sensor that controls CD8 T-cell memory. European journal of immunology. 43, 889-896
d.o.i 10.1002/eji.201243008
Pubmed: 3734624
PMC: 23310952
Finlay, D. K., Rosenzweig, E., Sinclair, L. V., Feijoo-Carnero, C., Hukelmann, J. L., Rolf, J., Panteleyev, A. A., Okkenhaug, K. and Cantrell, D. A. (2012) PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells. The Journal of experimental medicine. 209, 2441-2453
d.o.i 10.1084/jem.20112607
Pubmed: 3526360
PMC: 23183047
Navarro, M. N., Sinclair, L. V., Feijoo-Carnero, C., Clarke, R., Matthews, S. A. and Cantrell, D. A. (2012) Protein kinase D2 has a restricted but critical role in T-cell antigen receptor signalling in mature T-cells. The Biochemical journal. 442, 649-659
d.o.i 10.1042/BJ20111700
Pubmed: 3462612
PMC: 22233340
Grzes, K. M., Swamy, M., Hukelmann, J. L., Emslie, E., Sinclair, L. V. and Cantrell, D. A. (2017) Control of amino acid transport coordinates metabolic reprogramming in T-cell malignancy. Leukemia. 31, 2771-2779
d.o.i 10.1038/leu.2017.160
Pubmed: 5729345
PMC: 28546582
Eftimie, R., Gillard, J. J. and Cantrell, D. A. (2016) Mathematical Models for Immunology: Current State of the Art and Future Research Directions. Bulletin of mathematical biology. 78, 2091-2134
d.o.i 10.1007/s11538-016-0214-9
Pubmed: 5069344
PMC: 27714570
Frost, J., Galdeano, C., Soares, P., Gadd, M. S., Grzes, K. M., Ellis, L., Epemolu, O., Shimamura, S., Bantscheff, M., Grandi, P., Read, K. D., Cantrell, D. A., Rocha, S. and Ciulli, A. (2016) Potent and selective chemical probe of hypoxic signalling downstream of HIF-alpha hydroxylation via VHL inhibition. Nature communications. 7, 13312
d.o.i 10.1038/ncomms13312
Pubmed: 5097156
PMC: 27811928