Fellow of the Royal Society (UK National Academy of Sciences)
Member of Leopoldina (German National Academy of Sciences)
Academic Experience
2025-Present: Chief Scientist and Principal Investigator, Shanghai Institute of Immunity and Infection, CAS, China
2023-Present: Professor Emeritus and Principal Investigator, Sir William Dunn School of Pathology, University of Oxford, UK
2011-2022: Professor of Pathology, Wellcome Trust Principal Research Fellow, Head of Department of Pathology, University of Cambridge, UK
2000-2011: Professor of Virology, Wellcome Trust Principal Research Fellow, Head of Department of Virology, Imperial College London, UK
1989-2000: Reader in Bacteriology / Professor of Virology, Sir William Dunn School of Pathology, University of Oxford, UK
1985-1989: Lecturer in Virology, Department of Virology, University of Cambridge, UK
1981-1984: Postdoc, Dr Bernard Moss’s laboratory, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Maryland, USA
Education
1977-1981: Ph.D., Replication of the influenza virus genome. National Institute for Medical Research, London, UK
1974-1977: BSc (Hons) Microbiology and Biochemistry, University of Leeds, UK
Our lab studies poxviruses (including monkeypox virus, MPXV) and their interactions with the host cell and the immune system. In particular, we study host factors that restrict the replication of poxviruses and their molecular mechanisms of action, and how these viruses are able to evade these innate immune defences. These studies enhance understanding of how our immune system works, and how viruses evade this to cause disease. For example, studies of host proteins targeted by specific poxvirus proteins revealed that (1) SPIR-1 and HDAC5 promote activation of the transcription factor IRF3 (PLoS Pathogens 2022; Cell Reports, 2024), (2) HDAC4 is needed for type I interferon signaling (PNAS, 2019), (3) CBP is targeted by poxvirus protein F14 to block NF-κB induced gene expression (Nature Microbiol, 2022) and (4) TRIM5α is a restriction factor for poxviruses (Nature, 2023). This work has practical application in the development of anti-viral drugs (Nature 2023), and the engineering of poxviruses as vaccines of increased safety and potency against poxviruses and other pathogens.
The importance of continuing to study poxviruses has been highlighted by the emergence of clade II MPXV in 2022 to cause a global epidemic that WHO declared a public health emergency of international concern (PHEIC). In 2023, another MPXV epidemic started in central Africa caused by the more dangerous clade I MPXV. This has spread outside Africa to other countries including China, and in 2024 WHO again declared a PHEIC.
Research progress
Selected publications: since 2018
1. Scutts, S.R., Ember, S.W.J., Ren, H., Veyer, D.L., Sumner, R.P., Ye, C. & Smith, G.L. (2018). DNA-PK Is targeted by multiple vaccinia virus proteins to inhibit DNA sensing. Cell Reports 25, 1953-1965 e4. PMID 30428360
2. Neidel, S., Ren, H., Torres, A. & Smith, G.L. (2019). NF-κB activation is a turn on for vaccinia virus phosphoprotein A49 to turn off NF-κB activation. Proc. Natl. Acad. Sci. USA. 116, 5699-5704. PMID 30819886
3. Pallett, M.A., Ren, H., Zhang, R.-Y., Scutts, S.R., Gonzalez, L., Zhu, Z., Maluquer de Motes, C. & Smith, G.L. (2019). Vaccinia virus BBK E3 ligase adaptor A55 targets importin-dependent NF-κB activation and inhibits CD8+ T-cell memory. J. Virol. 93, e00051-19. PMID 30814284
4. Soday, L., Lu, Y., Albarnaz, J.D., Davies, C., Antrobus, R., Smith, G.L., & Weekes, M.P. (2019). Quantitative temporal viromics of vaccinia virus infection reveals regulation of histone deacetylases by a virus interferon antagonist. Cell Reports 27, 1920-33 e7. PMID 31067474
5. Lu, Y., Stuart, J.H., Talbot-Cooper, C., Agrawal-Singh, SA., Huntly, B., Smid, A.I., Snowden, J.S., Dupont, L., & Smith, G.L. (2019) Histone deacetylase 4 promotes type I interferon signalling, restricts DNA viruses, and is degraded by vaccinia virus protein C6. Proc. Natl. Acad. Sci. USA 116, 11997-12006. PMID 31127039
6. Meyer, H., Ehmann, R. and Smith, G.L. (2020). Smallpox in the post eradication era. Viruses 12, 138. PMID 31991671
7. Duggan, A.T., Klunk, J., Porter, A.F., Dhody, A.N., Hicks, R., Smith, G.L., Humphreys, M., McCollum, A.M., Davidson, W.B., Wilkins, K., Li, Y., Burke, A., Polasky, H., Flanders, L., Poinar, D., Raphenya, A.R., Lau, T.T.Y., Alcock, B., McArthur, A.G., Golding, G.B., Holmes, E.C. & Poinar, H.N. (2020). The origins and genomic diversity of American Civil War Era smallpox vaccine strains. Genome Biol. 21, 175. PMID 32684155
8. Mühlemann, B., Vinner L., Margaryan, A., Wilhelmson, H., de la Fuente Castro, C., Allentoft, M.E., de Barros Damgaard, P., Hansen, A.J., Holtsmark-Nielsen, S., Strand, L.M., Bill, J., Buzhilova, A., Pushkina, T., Falys, C., Khartanovich, V., Moiseyev, V., Jørkov, M.L.S., Østergaard Sørensen, P., Magnusson, Y., Gustin, I., Schroeder, H., Sutter, G., Smith, G.L., Drosten, C., Fouchier, R.A.M., Smith, D.J., & Willerslev, E. Jones, T.C., & Sikora, M. (2020). Diverse variola virus (smallpox) strains were widespread in Northern Europe in the Viking Age. Science, 369, issue 6502, 10.1126/science.aaw8977 PMID 32703849
9. Moss, B. & Smith, G.L. (2021). Research with variola virus after smallpox eradication: development of a mouse model for variola virus infection. PLoS Pathogens 17: e1009911.PMID 34547026
10. Peng, Y., Felce, S.L., Dong, D., Penkava, F., Mentzer, A.J., Yao, X., Liu, G., Yin, Z., Chen, J.L., Lu, Y., Wellington, D., Wing, P.A.C., Dominey-Foy, D.C.C., Jin, C., Wang, W., Hamid, M.A., Fernandes, R.A., Wang, B., Fries, A., Zhuang, X., Ashley, N., Rostron, T., Waugh, C., Sopp, P., Hublitz, P., Beveridge, R., Tan, T.K., Dold, C., Kwok, A.J., Rich-Griffin, C., Dejnirattisa, W., Liu, C., Kurupati, P., Nassiri, I., Watson, R.A., Tong, O., Taylor, C.A., Kumar Sharma, P., Sun, B., Curion, F., Revale, S., Garner, L.C., Jansen, K., Ferreira, R.C., Attar, M., Fry, J.W., Russell, R.A., Combat Consortium, Stauss, H.J., James, W., Townsend, A., Ho, L.P., Klenerman, P., Mongkolsapaya, J., Screaton, G.R., Dendrou, C., Sansom, S.N., Bashford-Rogers, R., Chain, B., Smith, G.L., McKeating, J.A., Fairfax, B.P., Bowness, P., McMichael, A.J., Ogg, G., Knight, J.C. & Dong, T. (2022). An immunodominant NP105-113 NP-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease Nature Immunol. 23, 50-61 PMID: 34853448
11. Albarnaz, J.D., Ren, H., Torres, A.A., Shmeleva, E.V., de Melo, C.M.A.G., Bannister, A.J. & Smith, G.L. (2022). Molecular mimicry of NF-kappaB by vaccinia virus protein enables selective inhibition of antiviral responses. Nature Microbiol. 7, 154-68. PMID 34949827
12. Gao, W.N.D., Gao, C., Deane, J.E., Carpentier, D.C.J., Smith, G.L. & Graham, S.C. (2022). The crystal structure of vaccinia virus protein E2 and perspectives on the prediction of novel viral protein folds. J. Gen. Virol. 103, 716- PMID 35020582
13. Talbot-Cooper, C., Pantelejevs, T., Shannon, J.P., Cherry, C.R., Au, M.T., Hyvönen, M., Hickman, H.D. & Smith, G.L. (2022). Poxviruses and paramyxoviruses use a conserved mechanism of STAT1 antagonism to inhibit interferon signaling. Cell Host Microbe 30, 1-16 PMID 35182467
14. Pallett, M.A., Lu, Y. & Smith, G.L. (2022). DDX50 Is a viral restriction factor that enhances IRF3 activation. Viruses 14, 316. PMID 30814284
15. Torres, A.A., Macilwee, S.L., Rashid, A., Cox, S.E., Albarnaz, J.D., Bonjardim, C. & Smith, G.L. (2022). The actin nucleator Spir-1 is a virus restriction factor that promotes innate immune signalling. PLoS Pathogens 18: e1010277. PMID 35148361
16. Shmeleva, E.V., Gomez de Agüero, M., Wagner, J., Enright, A.J., Macpherson, A.J., *Ferguson, B.J., & *Smith, G.L. (2022) Smallpox vaccination induces a substantial increase in commensal skin bacteria that promote pathology and influence the host response. PLoS Pathogens, 18, e1009854 PMID 35446919 *joint senior authorship.
17. Linville, A.C., Rico, A.B., Teague, H., Binsted, L.E., Smith, G.L., Albarnaz, J.D. & Wiebe, M.S. (2022) Dysregulation of cellular VRK1, BAF, and innate immune signaling by the vaccinia virus B12 pseudokinase. J. Virol. 96, e0039822. PMID e0039822
18. Depierreux, D.M*., Altenburg,, A.F*., Soday, L., Fletcher-Etherington, A., Anthrobus, R., Ferguson, B.J., Weekes, M.P**. & Smith, G.L**. (2022). Selective modulation of cell surface proteins during vaccinia infection: a resource for identifying viral immune evasion strategies. PLoS Pathogens 18, e1010612. PMID 35727847 * joint 1st authorship. ** joint senior authorship.
19. Zhang, R.-Y., Pallet, M.A., French, J., Ren, H. & Smith, G.L. (2022). Vaccinia virus BTB-Kelch proteins C2 and F3 inhibit NF-κB activation. J. Gen. Virol. 103, 1786- PMID 36301238
20. Lu, Y., Michel, H.A., Wang, P.-H. & Smith, G.L. (2022) Manipulation of innate immune signalling pathways by SARS-CoV-2 non-structural proteins. Front. Microbiol, 1027015 PMID 36478862
21. Yin, Z., Chen, J., Lu, Y., Wang, B., Godfrey, L., Mentzer, A.J., Yao, X., Liu, G., Wellington, D., Zhao, Y., Wing, P.A.C., Dejnirattisa, W., Supasa, P., Liu, C., Hublitz, P., Beveridge, R., Waugh, C., Clark, S.-A., Clark, K., Sopp, P., Rostron, T., Mongkolsapaya, J., Screaton, G.R., Ogg, G., Pollard, A., Gilbert, S., Knight, J.C., Lambe, T., Smith,, G.L., Dong, T. & Peng, Y. (2023) Evaluation of T cell responses to naturally processed variant SARS-CoV-2 spike antigens in individuals following infection or vaccination. Cell Reports, 42, 5, 112470. PMID 37141092
22. *Zhao, Y., *Lu, Y., Richardson, S., Sreekumar, M., Albarnaz, J.D. & Smith, G.L. (2023). TRIM5α restricts poxviruses and is antagonized by CypA and the viral protein C6. Nature, 620, 873–880. PMID 37558876 * joint 1st authorship.
23. Stewart, H.,, Lu, Y., O’Keefe, S., Valpadashi, A., Cruz-Zaragoza, L.D., Michel, H.A., Nguyen, S.K., Carnell, G.W., Lukhovitskaya, N., Milligan, R., Jungreis, I., Lulla, V., Davidson, A.D., Matthews, D.A., High, S., Rehling, P., Emmott, E., Heeney, J.L., Edgar, J.R., Smith, G.L, & Firth, A.E. (2023). The SARS-CoV-2 protein ORF3c is a mitochondrial modulator of innate immunity. iScience 26, 108080, PMID 37860693
24. Albarnaz, J.D. Oliveira, M., Kite, K., Paulo, J.A., Antrobus, R., Gygi, S.P., Huttlin, E.L, Smith, G.L. & Weekes, M.P. (2023). Quantitative proteomics defines mechanisms of antiviral defence and cell death during modified vaccinia Ankara infection Nature Comms., 14, 8134 PMID 38065956
25. Georgana, I., Scutts, S.R., Gao, C., Lu, Y., Ren, H., Emmontt, E., Men, J., Oei, K. & Smith, G.L. (2024). Filamin B restricts vaccinia virus spread and is targeted by vaccinia virus protein C4. J. Virol. e0148523, PMID 38412044
26. Lu, Y., Zhao, Y., Gao, C., Suresh, S., Men, J., Sawyers, A., & Smith, G.L. (2024). HDAC5 is a positive regulator of IRF3 activation and is targeted for degradation by protein C6 from orthopoxviruses including monkeypox virus and variola virus. Cell Reports 43, 113788 PMID 38461415
27. Jiao, P., Jia, X., Ma, J., Zhang, H., Zhao, Y., Fan, W., Bai, X., Zhang, H., Jia, X., Zhao, Y., Lu, Y., Guo, J., Zhang, K., Fang, M., Liu, W., Smith, G.L. & Sun, L. (2024). The nuclear localization signal of monkeypox virus protein P2 orthologues is critical for inhibition of IRF3-mediated innate immunity. Emerg Microbes Infect 13 (1), 2372344. PMID 38916407