Projects per year
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.
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
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Network
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Regulation and Function of Nucleoplasmin3 During Neuronal Differentiation (Clinical PhD Programme: Shuaibu Dambatta)
Cantrell, D., Lambert, J., Marshall, S. & Storey, K.
Project: Research
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NRF2 Activation Reprograms Defects in Oxidative Metabolism to Restore Macrophage Function in Chronic Obstructive Pulmonary Disease
Ryan, E. M., Sadiku, P., Coelho, P., Watts, E. R., Zhang, A., Howden, A. J. M., Sanchez-Garcia, M. A., Bewley, M., Cole, J., McHugh, B. J., Vermaelen, W., Ghesquiere, B., Carmeliet, P., Rodriguez Blanco, G., Von Kriegsheim, A., Sanchez, Y., Rumsey, W., Callahan, J. F., Cooper, G., Parkinson, N., & 8 others , 15 Apr 2023, In: American Journal of Respiratory and Critical Care Medicine. 207, 8, p. 998-1011 14 p.Research output: Contribution to journal › Article › peer-review
Open AccessFile3 Downloads (Pure) -
The immunological proteome resource
Brenes, A. J., Lamond, A. I. & Cantrell, D. A., May 2023, In: Nature Immunology. 24, 5, 1 p., 731.Research output: Contribution to journal › Letter › peer-review
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Concomitant deletion of Ptpn6 and Ptpn11 in T cells fails to improve anticancer responses
Ventura, P. M. O., Gakovic, M., Fischer, B. A., Spinelli, L., Rota, G., Pathak, S., Khameneh, H. J., Zenobi, A., Thomson, S., Birchmeier, W., Cantrell, D. A. & Guarda, G., 7 Nov 2022, In: EMBO Reports. 23, 11, 11 p., e55399.Research output: Contribution to journal › Article › peer-review
Open AccessFile1 Citation (Scopus)15 Downloads (Pure) -
Nrf2 activation reprograms macrophage intermediary metabolism and suppresses the type I interferon response
Ryan, D. G., Knatko, E. V., Casey, A. M., Hukelmann, J., Dayalan Naidu, S., Brenes, A. J., Ekkunagul, T., Baker, C., Higgins, M., Tronci, L., Nikitopolou, E., Honda, T., Hartley, R. C., O'Neill, L. A. J., Frezza, C., Lamond, A. I., Abramov, A. Y., Arthur, J. S. C., Cantrell, D. A., Murphy, M. P., & 1 others , 18 Feb 2022, In: iScience. 25, 2, 21 p., 103827.Research output: Contribution to journal › Article › peer-review
Open AccessFile26 Citations (Scopus)46 Downloads (Pure) -
Protein synthesis, degradation, and energy metabolism in T cell immunity
Marchingo, J. M. & Cantrell, D. A., Mar 2022, In: Cellular & Molecular Immunology. 19, p. 303-315 13 p.Research output: Contribution to journal › Review article › peer-review
Open AccessFile8 Citations (Scopus)85 Downloads (Pure)
Prizes
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Feldberg Prize - British Recipient
Cantrell, Doreen (Recipient), 2023
Prize: Prize (including medals and awards)
Activities
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Fuelling T cells
Doreen Cantrell (Speaker)
1 Nov 2022 → 5 Nov 2022Activity: Talk or presentation types › Invited talk
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T cell fate determination
Doreen Cantrell (Speaker)
2 Dec 2022Activity: Talk or presentation types › Invited talk