Professor David Withers PhD

Department of Immunology and Immunotherapy
Honorary Professor of Immune Regulation

Contact details

Telephone: +44 (0)121 414 8516
Email: d.withers@bham.ac.uk

Address: Department of Immunology and Immunotherapy
College of Medicine and Health
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

David Withers is an Honorary Professor of Immune Regulation.

Research in the Withers Lab is focused on understanding how memory CD4 T cell responses are generated and maintained, in particular the key cellular interactions that provide critical signals in this process. They are currently testing the role of RORgt-expressing group 3 Innate Lymphoid Cells versus other immune cell populations as checkpoints in adaptive immunity, both within secondary lymphoid tissue but also at mucosal barrier surfaces.

Qualifications

PhD Immunology, 2004
BSc (Hons) Microbiology and Virology, 2000

Biography

David Withers qualified with a BSc (Hons) in Virology and Microbiology from the University of Warwick in 2000. He went on to study for a PhD in Immunology at the Institute for Animal Health in conjunction with the University of Bristol. After obtaining his PhD, David continued his studies in the laboratory of Peter Lipsky at NIAMS, NIH, Bethseda (2004-2006). He then returned to the UK to study with Peter Lane at the University of Birmingham, cementing his interest in secondary lymphoid tissue development/structure and how this controlled CD4 T cell responses. Research in the Withers Lab is supported by the Wellcome Trust. In 2011 he was awarded a Wellcome Trust Research Career Development Fellowship to establish his own research group investigating the role of lymphoid tissue inducer cells in lymph nodes. In 2016 he was awarded a Wellcome Trust Senior Research Fellowship in Basic Biomedical Science. In 2024, Professor Withers moved his research group to the University of Oxford and retains Honorary Professor status at the University of Birmingham.

Teaching

Teaching Programmes

Postgraduate supervision

The Withers Lab currently has a full quota of PhD students and no capacity to take on more students at this time.

Research

Research themes

T cell responses, Innate Lymphoid Cells, Immunological memory.

Research activity

David's research is focused on understanding the signals involved in the development and maintenance of T cell responses, in particular, the development of memory CD4 T cells which are essential for immunological memory and thus vaccination. Understanding how memory CD4 T cells are generated and maintained is crucial for improving our ability to enhance vaccination, but also potentially to modulate unwanted self-reactivity. Much of our initial work has concentrated on cellular interactions within secondary lymphoid tissue, particularly with regard to the role of ROR t-dependent group 3 Innate Lymphoid Cells (ILC3s) in regulating CD4 T cell responses. As the lab has developed, our research has now broadened to assess epigenetic changes in T cells and ILCs, mucosal tissues as sites of effector T cell responses and models enabling in vivo assessment of immune cell migration. Most recently, we developed novel approaches to track immune cell migration into and out of tumours, establishing innovative new models that can reveal fundamental information regarding anti-tumour immunity. Research in my lab is currently focused in four complimentary areas:

Dissecting the roles of ILC3s in controlling T cell responses.
Analysis of memory Th1 and Th17 responses.
Understanding the role of key transcription factors in dictating ILC and T cell function and fate.
Analysis of immune cell recruitment and retention in tumours in vivo.

Publications

Recent publications

Article

Dean, I, Lee, CYC, Tuong, ZK, Li, Z, Tibbitt, CA, Willis, C, Gaspal, F, Kennedy, BC, Matei-Rascu, V, Fiancette, R, Nordenvall, C, Lindforss, U, Baker, SM, Stockmann, C, Sexl, V, Hammond, SA, Dovedi, SJ, Mjösberg, J, Hepworth, MR, Carlesso, G, Clatworthy, MR & Withers, DR 2024, 'Rapid functional impairment of natural killer cells following tumor entry limits anti-tumor immunity', Nature Communications, vol. 15, no. 1, 683. https://doi.org/10.1038/s41467-024-44789-z

Lee, CYC, Kennedy, BC, Richoz, N, Dean, I, Tuong, ZK, Gaspal, F, Li, Z, Willis, C, Hasegawa, T, Whiteside, SK, Posner, DA, Carlesso, G, Hammond, SA, Dovedi, SJ, Roychoudhuri, R, Withers, DR & Clatworthy, MR 2024, 'Tumour-retained activated CCR7⁺ dendritic cells are heterogeneous and regulate local anti-tumour cytolytic activity', Nature Communications, vol. 15, no. 1, 682. https://doi.org/10.1038/s41467-024-44787-1

Tachó-Piñot, R, Stamper, CT, King, JA, Matei-Rascu, V, Richardson, E, Li, Z, Roberts, LB, Bassett, JW, Melo-Gonzalez, F, Fiancette, R, Lin, I-H, Dent, A, Harada, Y, Finlay, C, Mjösberg, J, Withers, DR & Hepworth, MR 2023, 'Bcl6 is a subset-defining transcription factor of lymphoid tissue inducer-like ILC3', Cell Reports, vol. 42, no. 11, 113425. https://doi.org/10.1016/j.celrep.2023.113425

Clement, M, Ladell, K, Miners, KL, Marsden, M, Chapman, L, Cardus Figueras, A, Scott, J, Andrews, R, Clare, S, Kriukova, VV, Lupyr, KR, Britanova, OV, Withers, DR, Jones, SA, Chudakov, DM, Price, DA, Humphreys, IR, Jonjic, S (ed.) & Rath, S 2023, 'Inhibitory IL-10-producing CD4 + T cells are T-bet-dependent and facilitate cytomegalovirus persistence via coexpression of arginase-1', eLife, vol. 12, e79165. https://doi.org/10.7554/elife.79165

Anstee, JE, Feehan, KT, Opzoomer, JW, Dean, I, Muller, HP, Bahri, M, Cheung, TS, Liakath-Ali, K, Liu, Z, Choy, D, Caron, J, Sosnowska, D, Beatson, R, Muliaditan, T, An, Z, Gillett, CE, Lan, G, Zou, X, Watt, FM, Ng, T, Burchell, JM, Kordasti, S, Withers, DR, Lawrence, T & Arnold, JN 2023, 'LYVE-1⁺ macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer', Developmental Cell, vol. 58, no. 17, pp. 1548-1561.e10. https://doi.org/10.1016/j.devcel.2023.06.006

Kennedy, BC, Dean, I & Withers, DR 2023, 'Migration of stem-like CD8 T cells between tissue microenvironments underpins successful anti-tumour immune responses', Discovery Immunology, vol. 2, no. 1, kyad004. https://doi.org/10.1093/discim/kyad004

Molostvov, G, Gachechiladze, M, Shaaban, AM, Hayward, S, Dean, I, Dias, IHK, Badr, N, Danial, I, Mohammed, F, Novitskaya, V, Paniushkina, L, Speirs, V, Hanby, A, Nazarenko, I, Withers, DR, van Laere, S, Long, HM & Berditchevski, F 2023, 'Tspan6 stimulates the chemoattractive potential of breast cancer cells for B cells in an EV- and LXR-dependent manner', Cell Reports, vol. 42, no. 3, 112207. https://doi.org/10.1016/j.celrep.2023.112207

JRI Live Cell Bank, Lyu, M, Suzuki, H, Kang, L, Gaspal, F, Zhou, W, Goc, J, Zhou, L, Zhou, J, Zhang, W, Shen, Z, Fox, JG, Sockolow, RE, Laufer, TM, Fan, Y, Eberl, G, Withers, DR & Sonnenberg, GF 2022, 'ILC3s select microbiota-specific regulatory T cells to establish tolerance in the gut', Nature, vol. 610, no. 7933, pp. 744-751. https://doi.org/10.1038/s41586-022-05141-x

Li, Z, Tuong, ZK, Dean, I, Willis, C, Gaspal, F, Fiancette, R, Idris, S, Kennedy, B, Ferdinand, JR, Peñalver, A, Cabantous, M, Murtuza Baker, S, Fry, JW, Carlesso, G, Hammond, SA, Dovedi, SJ, Hepworth, MR, Clatworthy, MR & Withers, DR 2022, 'In vivo labeling reveals continuous trafficking of TCF-1+ T cells between tumor and lymphoid tissue', Journal of Experimental Medicine, vol. 219, no. 6, e20210749. https://doi.org/10.1084/jem.20210749, https://doi.org/10.1084/jem.20210749

Drummond, RA, Desai, JV, Ricotta, EE, Swamydas, M, Deming, C, Conlan, S, Quinones, M, Matei-Rascu, V, Sherif, L, Lecky, D, Lee, C-CR, Green, NM, Collins, N, Zelazny, AM, Prevots, DR, Bending, D, Withers, D, Belkaid, Y, Segre, JA & Lionakis, MS 2022, 'Long-term antibiotic exposure promotes mortality after systemic fungal infection by driving lymphocyte dysfunction and systemic escape of commensal bacteria', Cell Host & Microbe, vol. 30, no. 7, pp. 1020-1033.e6. https://doi.org/10.1016/j.chom.2022.04.013

Roberts, LB, Schnoeller, C, Berkachy, R, Darby, M, Pillaye, J, Oudhoff, MJ, Parmar, N, Mackowiak, C, Sedda, D, Quesniaux, V, Ryffel, B, Vaux, R, Gounaris, K, Berrard, S, Withers, DR, Horsnell, WGC & Selkirk, ME 2021, 'Acetylcholine production by group 2 innate lymphoid cells promotes mucosal immunity to helminths', Science Immunology, vol. 6, no. 57, eabd0359. https://doi.org/10.1126/sciimmunol.abd0359

Goc, J, Lv, M, Bessman, NJ, Flamar, A-L, Sahota, S, Suzuki, H, Teng, F, Putzel, GG, Eberl, G, Withers, DR, Arthur, JC, Shah, MA & Sonnenberg, GF 2021, 'Dysregulation of ILC3s unleashes progression and immunotherapy resistance in colon cancer', Cell, vol. 184, no. 19, pp. 5015-5030.e16. https://doi.org/10.1016/j.cell.2021.07.029

Papaioannou, NE, Salei, N, Rambichler, S, Ravi, K, Popovic, J, Küntzel, V, Lehmann, CHK, Fiancette, R, Salvermoser, J, Gajdasik, DW, Mettler, R, Messerer, D, Carrelha, J, Ohnmacht, C, Haller, D, Stumm, R, Straub, T, Jacobsen, SEW, Schulz, C, Withers, DR, Schotta, G, Dudziak, D & Schraml, BU 2021, 'Environmental signals rather than layered ontogeny imprint the function of type 2 conventional dendritic cells in young and adult mice', Nature Communications, vol. 12, no. 1, 464. https://doi.org/10.1038/s41467-020-20659-2

Kästele, V, Mayer, J, Lee, ES, Papazian, N, Cole, JJ, Cerovic, V, Belz, G, Tomura, M, Eberl, G, Goodyear, C, Maciewicz, RA, Wall, D, Cupedo, T, Withers, DR & Milling, S 2021, 'Intestinal-derived ILCs migrating in lymph increase IFNγ production in response to Salmonella Typhimurium infection', Mucosal immunology, vol. 14, no. 3, pp. 717-727. https://doi.org/10.1038/s41385-020-00366-3

Review article

Lee, CYC, Clatworthy, MR & Withers, DR 2024, 'Decoding changes in tumor‐infiltrating leukocytes through dynamic experimental models and single‐cell technologies', Immunology and Cell Biology. https://doi.org/10.1111/imcb.12787

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