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Professor Geoffrey L Smith

Professor Geoffrey L Smith

Professor of Pathology

Division of Virology

Head of Department

Wellcome Trust Principal Research Fellow

Project: Poxvirus research group

Department of Pathology
University of Cambridge
Tennis Court Road
Cambridge
CB2 1QP

Office Phone: +44 (0)1223 333692

Research themes

Virology:

Research Interests

The Smith research group is housed within modern, well-equipped laboratories in the main Pathology Building in Tennis Court Road in central Cambridge. The research team is supported by grants from the Wellcome Trust and Medical Research Council and GLS is a Wellcome Trust Principal Research Fellow. 

The lab is composed of a visiting scientist, postdocs, PhD students, master students, undergraduates and technicians. The lab is very international with the majority of members coming from outside the United Kingdom.

The research team studies vaccinia virus, the vaccine used to eradicate smallpox, and the interactions between this virus and the host cell and immune system. Areas of research include investigation of how vaccinia virus suppresses the innate immune response to infection, how individual virus proteins contribute to virus virulence and immunogenicity, how safer and more immunogenic vaccines can be designed, and how vaccinia virus exploits microtubule- and actin-based transport to enable transport of virions within and between cells. In addition, vaccinia virus is being exploited as a tool to study the function of cell proteins and how these restrict the replication or spread of viruses, or how they activate the immune response to infection.

 

Postdoctoral fellows

  • Altenburg, Arwen
  • Carpentier, David
  • Dutra Albarnaz, Jonas
  • Gao, Chen
  • Georgana, Iliana
  • Lu, Yongxu
  • Shmeleva, Evgeniya
  • Torres, Alice

Visiting Scientist

  • Li, Dong

Technicians

  • Hollinshead, Michael
  • Macilwee, Stephanie

PhD students

  • Depierreux, Delphine
  • Talbot-Cooper, Callum
  • Zhang, Rui-Yao
  • Zhong, Qi

Undergraduate Research Students

  • Chan, Andrew
  • Cooper, Samuel
  • Men, Jinghao

 

Key Publications

1.    Doceul, V., Hollinshead, M., van der Linden, L. & Smith, G.L. (2010). Repulsion of superinfecting virions: a mechanism for rapid virus spread. Science, 327, 873-7.

2.    Ferguson, B.J., Mansur, D., Peters, N.E., Ren, H. & Smith, G.L (2012). DNA-PK is a DNA sensor for IRF-3 dependent innate immunity. eLife 1, 0047.

3.    Mansur, D.S., Maluquer de Motes, C., Unterholzner, L., Sumner, R.P., Ferguson, B.J., Ren, H., Strnadova, P., Bowie, A.G. & Smith, G.L. (2013). Poxvirus targeting of β-TrCP by molecular mimicry: a mechanism to inhibit NF-κB activation and promote immune evasion and virulence. PLoS Pathogens 9, e1003183.

4.    Mazzon, M., Peters, N.E., Loenarz, C., Krysztofinska, E., Ember, S.W.J., Ferguson, B.J., & Smith, G.L. (2013). A mechanism for the induction of a hypoxic response by vaccinia virus. Proc. Natl. Acad. Sci. USA. 110, 12444-9.

5.    Peters, N.E., Ferguson, B.J., Mazzon, M., Fahy, A.S., Krysztofinska, E., Arribas-Bosacoma, R., Pearl, L.H., Ren, H. & Smith, G.L. (2013). A mechanism for the inhibition of DNA-PK-mediated DNA sensing by vaccinia virus. PLoS Pathogens. 9, e1003649.

6.    Carpentier, D.C.J., Gao, W.N.D., Ewles, H., Morgan, G.W. & Smith, G.L. (2015). Vaccinia virus protein complex F12/E2 interacts with kinesin light chain isoform 2 to engage the kinesin-1 motor complex. PLoS Pathogens. 11, e1004723.

7.    Strnadova, P., Ren, H., Valentine, R., Mazzon, M., Brierley, I. & Smith, G.L. (2015). Inhibition of translation initiation by protein 169: a vaccinia virus strategy to compromise innate and adaptive immunity and alter virus virulence. PLoS Pathogens. 11, e1005151.

8.    Stuart, J.H., Sumner, R.P., Lu, Y., Snowden, J.S. & Smith, G.L. (2016). Vaccinia virus protein C6 inhibits type I IFN signaling in the nucleus and binds to the transactivation domain of STAT2. PLoS Pathogens. 12, e1005955.

9.    Scutts, S.R., Ember, S.W.J., Ren, H., Veyer, D.L., Sumner, R.P., Ye, C. & Smith, G.L. (2018) Vaccinia virus encodes a second DNA-PK inhibitor to evade DNA sensing. Cell Reports 25, 1953-1965 e4.

10.  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. 

11.  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.

12.  Gao, C., Pallett, M.A., Croll, T.I., Smith, G.L. & Graham, S.C. (2019). Molecular basis of Cul3 ubiquitin ligase subversion by vaccinia virus protein A55. J. Biol. Chem. 294, 6416-29. 

13.  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.

14.  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.