Professor Doreen Cantrell

CBE FRS FRSE FMedSci

Wellcome Trust Principal Research Fellow

Cell Signalling and Immunology, School of Life Sciences

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Contact

Email

d.a.cantrell@dundee.ac.uk

Phone

+44 (0)1382 385156

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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Awards

Award Year
International Science Prizes awarded since 1990 / Feldberg Prize - British Recipient 2023
PiCLS Best Mentor Award 2022
National Sciences Prizes awarded since 1990 / Lifetime Honorary Membership of the British Society for Immunology 2019
Personal Fellowships / Wellcome Trust Principal Research Fellowship 2017
National Sciences Prizes awarded since 1990 / Novartis Medal and Prize of the Biochemical Society 2017
Commander of the British Empire (CBE) 2014
Personal Fellowships / Wellcome Trust Principal Research Fellowship 2012
Fellow of the Royal Society 2011
Fellow of the Royal Society of Edinburgh 2005
Member of the European Molecular Biology Organisation 2000

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