Cantrell, Doreen

Professor

19992022
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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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  • 7 Similar Profiles
T-Lymphocytes Medicine & Life Sciences
T-cells Chemical Compounds
Antigen Receptors Medicine & Life Sciences
Protein-Serine-Threonine Kinases Medicine & Life Sciences
T-Cell Antigen Receptor Medicine & Life Sciences
Phosphotransferases Medicine & Life Sciences
Chemical activation Chemical Compounds
Interleukin-2 Medicine & Life Sciences

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Projects 2012 2022

Research Output 1999 2019

Move to metabolism

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

Research output: Contribution to journalComment/debate

Calcium-Calmodulin-Dependent Protein Kinases
AMP-Activated Protein Kinases
T-Cell Antigen Receptor
Phosphotransferases
Adenosine Triphosphate
10 Downloads (Pure)

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
Phenformin
AMP-Activated Protein Kinases
T-cells
Metformin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
13 Citations (Scopus)
29 Downloads (Pure)

Amino acid-dependent cMyc expression is essential for NK cell metabolic and functional responses in mice

Loftus, R. M., Assmann, N., Kedia-Mehta, N., O'Brien, K. L., Garcia, A., Gillespie, C., Hukelmann, J. L., Oefner, P. J., Lamond, A. I., Gardiner, C. M., Dettmer, K., Cantrell, D. A., Sinclair, L. V. & Finlay, D. K., 14 Jun 2018, In : Nature Communications. 9, 1, p. 1-15 15 p., 2341.

Research output: Contribution to journalArticle

Open Access
File
Natural Killer Cells
mice
amino acids
Lymphocytes
Glutamine
2 Citations (Scopus)
93 Downloads (Pure)

Interleukin-2 shapes the cytotoxic T cell proteome and immune environment sensing programs

Rollings, C., Sinclair, L., Brady, H. J. M., Cantrell, D. & Ross, S., 17 Apr 2018, In : Science Signaling. 11, 526, p. 1-16 16 p., eaap8112.

Research output: Contribution to journalArticle

Open Access
File
T-cells
Proteome
Interleukin-2
T-Lymphocytes
Cytotoxic T-Lymphocytes
8 Citations (Scopus)
66 Downloads (Pure)

Signaling and Function of Interleukin-2 in T Lymphocytes

Ross, S. H. & Cantrell, D. A., 26 Apr 2018, In : Annual Review of Immunology. 36, p. 411-433 23 p.

Research output: Contribution to journalArticle

Open Access
File
Interleukin-2
T-Lymphocytes
STAT5 Transcription Factor
Janus Kinases
Interleukin-2 Receptors

Activities 2014 2019

  • 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