Dr David Bending

Dr David Bending

Institute of Immunology and Immunotherapy
Birmingham Fellow

Contact details

Address
Institute of Immunology and Immunotherapy
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

T cell immunologist specialising in tolerance, immune regulation, and immunotherapy.

Qualifications

  • PhD in Immunologym University of Cambridge, 2011
  • BA (Hons) Medical Sciences, University of Cambridge, 2007

Biography

Dr David Bending is a T cell immunologist specialising in the regulation of T cell responses and T cell receptor (TCR) signalling. In 2018, he formed his own research group at the University of Birmingham, UK. His lab is supported by Wellcome Trust funding and an MRC Career Development fellowship. Their research focuses on how TCR signalling strength and dynamics regulate T cell function. Dr Bending's lab has keen interests in understanding how immunotherapy can alter T cell activation and identify favourable T cell signatures of therapy responders. They have developed cutting-edge TCR signalling research tools, such as the Timer of cell kinetics and activity (Tocky) system, to study T cell activation in vivo. Through exploiting the Tocky tool, a recent major finding is the discovery of the novel “TCR.strong” signalling signature, which is a hallmark of effective T cell responses to anti-PD1 immunotherapy.

Teaching

Postgraduate supervision

Currently students

  • 1 MSc by Research in Immunology and Immunotherapy student
  • 1 PhD in Immunology and Immunotherapy student

Research

Research interests

T cell receptor signalling, T cell activation, T cell regulation, Nr4a receptors, Immunotherapy, Tumour immunology, negative feedback control of T cells

Current projects

Negative feedback control of T cells in tolerance and cancer - from pathways to biomarkers

T cells are vital immune cells that help fight infections and cancer. T cells must strike a balance between successfully clearing harmful invaders and the collateral damage they might inflict in achieving this (called immunopathology). The T cell system therefore has many brakes which it can apply to control the level of immune response.  We have developed new tools that can follow T cell responses and identify when and how they switch on these immune brakes. We believe that these brakes that have developed to prevent autoimmunity account for why T cells are prevented from killing cancer cells.

Role of Nr4a receptors in T cell activation

Nr4a receptors are rapidly activated following TCR signalling and can be used to follow T cell activation processes in vivo. We use genetic tools to understand the roles Nr4a1 and Nr4a3 play in feedback control of the T cell activation process.

Role of TCR signal dynamics in the regulation of IL-10 expression

IL-10 is an important cytokine that modulates immune responses. Here we use state-of-the-art tools to understand under what conditions IL-10 is activated in T cells, and how TCR signal strength and dynamics control this process.

Other activities

Publications

Recent publications

Article

Elliot, T, Jennings, E, Lecky, D, Thawait, N, Flores-Langarica, A, Copland, A, Maslowski, K, Wraith, D & Bending, D 2021, 'Antigen and checkpoint receptor engagement recalibrates T cell receptor signal strength', Immunity. https://doi.org/10.1016/j.immuni.2021.08.020

Jennings, E, Lecky, D, Ono, M & Bending, D 2021, 'Application of dual Nr4a1-GFP Nr4a3-Tocky reporter mice to study T cell receptor signaling by flow cytometry', STAR Protocols, vol. 2, no. 1, 100284. https://doi.org/10.1016/j.xpro.2020.100284

Jennings, E, Elliot, T, Thawait, N, Kanabar, S, Yam-Puc, JC, Ono, M, Toellner, K-M, Wraith, DC, Anderson, G & Bending, D 2020, 'Nr4a1 and Nr4a3 reporter mice are differentially sensitive to T cell receptor signal strength and duration', Cell Reports, vol. 33, no. 5, 108328. https://doi.org/10.1016/j.celrep.2020.108328, https://doi.org/10.1016/j.celrep.2020.108328

Bending, D, Prieto Martin, P, Paduraru, A, Ducker, C, Marzaganov, E, Laviron, M, Kitano, S, Miyachi, H, Crompton, T & Ono, M 2018, 'A Timer for analyzing temporally dynamic changes in transcription during differentiation in vivo', Journal of Cell Biology, vol. 217, no. 8, pp. 2931-2950. https://doi.org/10.1083/jcb.201711048

Bending, D, Paduraru, A, Ducker, C, Prieto Martin, P, Crompton, T & Ono, M 2018, 'A temporally dynamic Foxp3 autoregulatory transcriptional circuit controls the effector Treg programme', The EMBO journal, vol. 37, no. 16, e99013. https://doi.org/10.15252/embj.201899013

Rosser, E, Lom, H, Bending, D, Duurland, C, Bajaj-Elliott, M & Wedderburn, LR 2018, 'Brief report: Innate lymphoid cells and T-cells contribute to the IL-17A signature detected in the synovial fluid of patients with Juvenile Idiopathic Arthritis', Arthritis and Rheumatology. https://doi.org/10.1002/art.40731

Bending, D & Ono, M 2017, 'Interplay between the skin barrier and immune cells in patients with atopic dermatitis unraveled by means of mathematical modeling', Journal of Allergy and Clinical Immunology, vol. 139, no. 6, pp. 1790-1792. https://doi.org/10.1016/j.jaci.2017.03.015

Bending, D, Giannakopoulou, E, Lom, H & Wedderburn, LR 2015, 'Synovial Regulatory T Cells Occupy a Discrete TCR Niche in Human Arthritis and Require Local Signals To Stabilize FOXP3 Protein Expression', Journal of Immunology, vol. 195, no. 12, pp. 5616-5624. https://doi.org/10.4049/jimmunol.1500391

Bending, D, Pesenacker, AM, Ursu, S, Wu, Q, Lom, H, Thirugnanabalan, B & Wedderburn, LR 2014, 'Hypomethylation at the regulatory T cell-specific demethylated region in CD25hi T cells is decoupled from FOXP3 expression at the inflamed site in childhood arthritis', Journal of Immunology, vol. 193, no. 6, pp. 2699-2708. https://doi.org/10.4049/jimmunol.1400599

Piper, C, Pesenacker, AM, Bending, D, Thirugnanabalan, B, Varsani, H, Wedderburn, LR & Nistala, K 2014, 'T cell expression of granulocyte-macrophage colony-stimulating factor in juvenile arthritis is contingent upon Th17 plasticity', Arthritis & Rheumatology (Hoboken), vol. 66, no. 7, pp. 1955-1960. https://doi.org/10.1002/art.38647

Pesenacker, AM, Bending, D, Ursu, S, Wu, Q, Nistala, K & Wedderburn, LR 2013, 'CD161 defines the subset of FoxP3+ T cells capable of producing proinflammatory cytokines', Blood, vol. 121, no. 14, pp. 2647-58. https://doi.org/10.1182/blood-2012-08-443473

Comment/debate

Bending, D & Ono, M 2017, 'FoxP3 partners up', Nature Immunology, vol. 18, no. 11, pp. 1181-1183. https://doi.org/10.1038/ni.3852

Review article

Copland, A & Bending, D 2018, 'Foxp3 molecular dynamics in Treg in juvenile idiopathic arthritis', Frontiers in immunology, vol. 9, 2273. https://doi.org/10.3389/fimmu.2018.02273

Bending, D & Ono, M 2018, 'From stability to dynamics: understanding molecular mechanisms of regulatory T cells through Foxp3 transcriptional dynamics', Clinical & Experimental Immunology. https://doi.org/10.1111/cei.13194

Working paper

Elliot, TAE, Jennings, EK, Lecky, DAJ, Thawait, N, Flores-Langarica, A, Wraith, DC & Bending, D 2021 'Antigen and checkpoint receptor recalibration of T cell receptor signal strength' bioRxiv, pp. 1-48. https://doi.org/10.1101/2021.03.02.431957

View all publications in research portal