Dr Sarah Dimeloe PhD

Sarah Dimeloe

Institute of Immunology and Immunotherapy
Institute of Metabolism and Systems Research
Birmingham Fellow
European Commission Marie Sklodowska Curie Fellow, Leukemia UK John Goldman Fellow

Contact details

Telephone
+44 (0)121 414 7442
Email
s.k.dimeloe@bham.ac.uk
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Address
Institute of Immunology and Immunotherapy
College of Medical and Dental Sciences
IBR, University of Birmingham
Edgbaston
Birmingham
B15 2TT

Sarah Dimeloe is a Birmingham Fellow working across the Institutes of Immunology and Immunotherapy (III), and Metabolism and Systems Research (IMSR).

Research in Sarah’s lab is focused on the metabolism of immune cells and how this underpins their role in health and disease.

Dr Dimeloe is a member of the 2017/18 Birmingham Fellows.

Qualifications

  • PhD Immunology, 2012
  • MSc Immunology, 2008
  • MPharm Pharmacy, 2004

Biography

Sarah Dimeloe qualified with an MPharm (Hons) from the University of Nottingham in 2004. She then completed her professional training as a pharmacist at Guy’s and St. Thomas’ NHS Foundation Trust. 

In 2007, Sarah undertook an MSc in Immunology at King’s College London (KCL), prior to completing her PhD in Immunology at KCL under the supervision of Professor Catherine Hawrylowicz. During her PhD, Sarah investigated the biology of CD4+ T lymphocytes in allergic and asthmatic disease.

In 2012 Sarah moved to the University of Basel in Switzerland to undertake post-doctoral research in the laboratory of Professor Christoph Hess. Here, Sarah began to investigate metabolic activity in T cells and how that relates to their important roles in health and disease. 

In 2017 Sarah was awarded a Birmingham Fellowship to establish her own research group at the University of Birmingham.

Postgraduate supervision

For any doctoral research enquiries, please email: s.k.dimeloe@bham.ac.uk

Research

Current research interests in Sarah Dimeloe’s lab focus on the metabolism and interlinked immune function of T lymphocytes in health and disease.

T lymphocytes comprise two subsets: CD4+ T cells, which co-ordinate immune responses against infections or cancers and CD8+ T cells, which can kill infected or cancerous cells of the body, as well as producing important cytokines (messenger molecules). Following an immune response, “memory” populations of both of these cell types remain in the body, surveying for reappearance of a threat, to which they are able to rapidly respond, in order to protect us.

During her post-doctoral research in Basel, Sarah identified a key signal instructing the required changes in metabolism in order for CD4+ T cells to coordinate an immune response. This signal was the binding of the innate immune molecule, complement C3b, to its receptor CD46 on the surface of CD4+ T cells. Sarah additionally worked to define the key metabolic traits of memory T cells that enable them to perform their specialised role. For example, Sarah identified that memory CD4+ T cells have large and complex mitochondria, enabling them to survive in, and patrol oxygen-poor environments like peripheral tissues of the body. She also contributed to work identifying that memory CD8+ T cells are metabolically “primed” to rapidly respond to threats.

In Birmingham, Sarah is now developing this research further to ask questions about how these “normal” metabolic functions are dysregulated in disease, and importantly, if such perturbations can be targeted to restore optimal T cell function and protection from disease. Specifically, Sarah is investigating changes in the use of key nutrients by T cells during their development and in disease states. Additionally, she working to identify components of diseased tissues that may subvert T cell metabolism and interlinked immune function and delineate the mechanisms involved, with the aim of discovering potential therapeutic targets. One experimental approach that Sarah is using to ask these questions is to perform high-resolution metabolic tracing analyses, by working together with the Metabolic Tracer Analysis Core (MTAC) facility at the University of Birmingham.

Publications

Recent publications

Article

Bishop, EL, Gudgeon, NH, Mackie, GM, Chauss, D, Roberts, J, Tennant, DA, Maslowski, KM, Afzali, B, Hewison, M & Dimeloe, S 2022, '1,25-Dihydroxyvitamin D3 suppresses CD4+ T-cell effector functionality by inhibition of glycolysis', Immunology, vol. 166, no. 3, pp. 299-309. https://doi.org/10.1111/imm.13472

Fletcher, J, Bishop, E, Harrison, S, Williamson-Swift, A, Cooper, SC, Dimeloe, S, Raza, K & Hewison, M 2022, 'Autoimmune disease and interconnections with vitamin D', Endocrine Connections, vol. 11, no. 3, e210554. https://doi.org/10.1530/EC-21-0554

Gudgeon, N, Munford, H, Bishop, EL, Hill, J, Fulton-Ward, T, Bending, D, Roberts, J, Tennant, DA & Dimeloe, S 2022, 'Succinate uptake by T cells suppresses their effector function via inhibition of mitochondrial glucose oxidation', Cell Reports, vol. 40, no. 7, 111193. https://doi.org/10.1016/j.celrep.2022.111193

Garcia, AM, Bishop, E, Li, D, Jeffery, L, Garten, A, Thakker, A, Certo, M, Mauro, C, Tennant, DA, Dimeloe, S, Evelo, CT, Coort, SL & Hewison, M 2021, 'Tolerogenic effects of 1,25-dihydroxyvitamin D on dendritic cells involve induction of fatty acid synthesis', The Journal of Steroid Biochemistry and Molecular Biology, vol. 211, 105891. https://doi.org/10.1016/j.jsbmb.2021.105891

Kolev, M, West, EE, Kunz, N, Chauss, D, Moseman, EA, Rahman, J, Freiwald, T, Balmer, ML, Lötscher, J, Dimeloe, S, Rosser, EC, Wedderburn, LR, Mayer-Barber, KD, Bohrer, A, Lavender, P, Cope, A, Wang, L, Kaplan, MJ, Moutsopoulos, NM, McGavern, D, Holland, SM, Hess, C, Kazemian, M, Afzali, B & Kemper, C 2020, 'Diapedesis-Induced Integrin Signaling via LFA-1 Facilitates Tissue Immunity by Inducing Intrinsic Complement C3 Expression in Immune Cells', Immunity, vol. 52, no. 3, pp. 513-527.e8. https://doi.org/10.1016/j.immuni.2020.02.006

Bishop, E, Ismailova, A, Dimeloe, SK, Hewison, M & White, JH 2020, 'Vitamin D and immune regulation: antibacterial, antiviral, anti-inflammatory', JBMR Plus. https://doi.org/10.1002/jbm4.10405

Nageswara Rao, T, Hansen, N, Hilfiker, J, Rai, S, Majewska, JM, Lekovic, D, Gezer, D, Andina, N, Galli, S, Cassel, T, Geier, F, Delezie, J, Nienhold, R, Hao-Shen, H, Beisel, C, Di Palma, S, Dimeloe, S, Trebicka, J, Wolf, D, Gassmann, M, Fan, TW, Lane, AN, Handschin, C, Dirnhofer, S, Kroger, N, Hess, C, Radimerski, T, Koschmieder, S, Cokic, VP & Skoda, RC 2019, 'JAK2 mutant hematopoietic cells display metabolic alterations that can be targeted to treat myeloproliferative neoplasms', Blood, vol. 134, no. 21, pp. 1832-1846. https://doi.org/10.1182/blood.2019000162

Burgener, A-V, Bantug, G, Meyer, B, Higgins, R, Ghosh, A, Bignucolo, O, Ma, E, Loeliger, J, Unterstab, G, Geigges, M, Steiner, R, Enamorado, M, Ivanek, R, Hunziker, D, Schmidt, R, Muller_Durovic, B, Graehlert, J, Epple, R, Dimeloe, S, Lotscher, J, Sauder, U, Ebnother, M, Burger, B, Heijnen, I, Martinez-Cano, S, Cantoni, N, Brucker, R, Kahlert, CR, Sancho, D, Jones, RG, Navarini, A, Recher, M & Hess, C 2019, 'SDHA gain-of-function engages inflammatory mitochondrial retrograde signaling via KEAP1-Nrf2', Nature Immunology, vol. 20, no. 10, pp. 1311–1321. https://doi.org/10.1038/s41590-019-0482-2

Dimeloe, S, Gubser, P, Loeliger, J, Frick, C, Develioglu, L, Fischer, M, Marquardsen, F, Bantug, GR, Thommen, DS, Lecoultre, Y, Zippelius, A, Langenkamp, A & Hess, C 2019, 'Tumor-derived TGF-β inhibits mitochondrial respiration to suppress IFN-γ production by human CD4+ T cells', Science signaling, vol. 12, no. 599, eaav3334. https://doi.org/10.1126/scisignal.aav3334

Dimeloe, S, Rice, L, Chen, H, Cheadle, C, Pfeffer, P, Lavender, P, Richards, D, Nyon, M, MacDonald, J, Kemper, C, Gooptu, B & Hawrylowicz, C 2019, 'Vitamin D (1,25(OH)2D3) induces α-1-antitrypsin synthesis by CD4+ T cells, which is required for 1,25(OH)2D3-driven IL-10.', The Journal of Steroid Biochemistry and Molecular Biology.

Thommen, DS, Koelzer, VH, Herzig, P, Roller, A, Trefny, M, Dimeloe, S, Kiialainen, A, Hanhart, J, Schill, C, Hess, C, Savic Prince, S, Wiese, M, Lardinois, D, Ho, P-C, Klein, C, Karanikas, V, Mertz, KD, Schumacher, TN & Zippelius, A 2018, 'A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade', Nature Medicine. https://doi.org/10.1038/s41591-018-0057-z

Editorial

Dimeloe, S & Mauro, C 2019, 'Translating immunometabolism: towards curing human diseases by targeting metabolic processes underpinning the immune response', Clinical & Experimental Immunology, vol. 197, no. 2, pp. 141-142. https://doi.org/10.1111/cei.13347

Review article

Pallett, LJ, Dimeloe, S, Sinclair, LV, Byrne, AJ & Schurich, A 2021, 'A glutamine 'tug-of-war': targets to manipulate glutamine metabolism for cancer immunotherapy', Immunotherapy Advances, vol. 1, no. 1, ltab010. https://doi.org/10.1093/immadv/ltab010

Bishop, EL, Gudgeon, N & Dimeloe, S 2021, 'Control of T Cell Metabolism by Cytokines and Hormones', Frontiers in immunology, vol. 12, 653605. https://doi.org/10.3389/fimmu.2021.653605

Munford, H & Dimeloe, S 2019, 'Intrinsic and Extrinsic Determinants of T Cell Metabolism in Health and Disease', Frontiers in Molecular Bioscience, vol. 6, pp. 118. https://doi.org/10.3389/fmolb.2019.00118

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