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Dr Brian Ferguson

Dr Brian Ferguson

University Lecturer

Division of Immunology

Project: Innate immune signalling, anti-viral immunity, vaccinology

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

Office Phone: +44 (0)1223 333730

Research themes

Immunology:

Division

Immunology:

Research Interests

Ferguson Research

The lab’s research projects are focused around understanding how our cells sense and respond to virus infection and how this impacts innate and adaptive immunity: 

1) The innate immune response to DNA.

Pattern recognition receptors (PRRs) directly recognise pathogen- or danger-associated molecular patterns. Nucleic acids are a powerful immunostimulatory agents that triggers PRRs to warm of infection or tissue damage. Our innate immune system has evolved multiple mechanisms to respond to the presence of abnormally structured or mis-localised DNA and RNA. We are exploring the molecular mechanisms of innate immune nucleic acid sensing and is physiological consequences across multiple species.

Nucleic acid sensing by intracellular PRRs has a particular importance in triggering the initial type I and type III interferon responses in response to virus infections. Our lab is interested to understand how different nucleic acid sensing PRRs impact on host defence against a range of DNA and RNA viruses.

2) Cell death in innate immunity

The role of cell death in anti-viral defence is well establised, although its function in activating anti-viral immunity is less clear. By analysing signalling pathways that control the switch between pro-inflammatory gene activation and cell death we can probe the consequences of viral-induced cell death in anti-viral defence. We are specifically interested in the role of linear ubiqiutin chains in regulating these processes and how they regulate nucleic acid sensing mechanisms.

3) Vaccinology

There are many fundamental questions about the development of immunological memory which remain poorly understood. It is clear that the initial detection of a vaccine vector by the innate immune system has long lasting consequences for the development of memory responses. We are developing systems to analyse how and where the initial triggers of long lasting memory occur.

Post-doctoral research associates:

Dr Evgenia Shmeleva
Dr Marisa Oliveira

PhD students:

Ms Delphine Depierreux
Ms Helena Teague
Ms Dayana Hristova
Ms Emma Wagner
Mr Rahul Singh

Masters students:

Ms Natasha Brett

Key Publications

Enhanced Efficacy of Vaccination With Vaccinia Virus in Old vs. Young Mice
E Shmeleva, GL Smith, BJ Ferguson
Front. Immunol., https://doi.org/10.3389/fimmu.2019.01780

2019

ISG15-Induced IL-10 Is a Novel Anti-Inflammatory Myeloid Axis Disrupted during Active Tuberculosis
PF dos Santos, J Van Weyenbergh, M Delgobo, DO Patricio, BJ Ferguson, R Guabiraba, T Dierckx, SM Menezes, A Bafica, DS Mansur
Journal of Immunology, ji1701120

2018

The Non-Homologous End Joining Protein PAXX Acts to Restrict HSV-1 Infection
BJ Trigg, KB Lauer, PF dos Santos, H Coleman, G Balmus, DS Mansur and BJ Ferguson
Viruses 9(11), 342; doi:10.3390/v9110342 

2017
Genome-wide analyses reveal a highly conserved Dengue virus envelope peptide which is critical for virus viability and antigenic in humans
RC Fleith, FP Lobo, PF dos Santos, MM Rocha, J Bordignon, DM Strottmann, DO Patricio, WR Pavanelli, M Lo Sarzi, CN Dos Santos, BJ Ferguson, DS Mansur
Scientific Reports 6, Article number: 36339
2016
LUBAC deficiency perturbs TLR3 signaling to cause immunodeficiency and autoinflammation
J Zinngrebe, E Rieser, L Taraborrelli, N Peltzer, T Hartwig, H Ren, I Kovács, C Endres, P Draber, M Darding, S von Karstedt, J Lemke, B Dome, M Bergmann , BJ Ferguson*, H Walczak*
J Experimental Medicine (In Press)
2016
Increased attenuation but decreased immunogenicity by deletion of multiple vaccinia virus immunomodulators
RP Sumner, H Ren, BJ Ferguson, GL Smith
Vaccine Volume 34, Pages 4827–4834
2016
The Schistosoma mansoni T2 ribonuclease omega-1 modulates inflammasome-dependent IL-1beta secretion in macrophages
BJ Ferguson, S Newland, SE Gibbs, P Tourlomousis, P Fernandes dos Santos, MN Patel, SW Hall, H Walczak, G Schramm, H Haas, DW Dunne, A Cooke, and P Zaccone
International Journal for Parasitology Volume 45, Issue 13 Pages 809–813
2015
Functions of DNA damage machinery in the innate immune response to DNA virus infection
BJ Trigg and BJ Ferguson
Current Opinion in Virology Volume 15, Pages 56–62
2015
International Union of Basic and Clinical Pharmacology. XCVI. Pattern Recognition Receptors in Health and Disease
CE Bryant, S Orr, BJ Ferguson, MF Symmons, JP Boyle, and TP Monie
Pharmacological Reviews vol. 67 no. 2 462-504
2015
Enhancement of CD8+ T‐cell memory by removal of a vaccinia virus NF‐κB inhibitor
H Ren, BJ Ferguson, C Maluquer de Motes, RP Sumner, L Harman, GL Smith
Immunology 145 (1), 34-49
2015
A mechanism for the inhibition of DNA-PK mediated DNA sensing by a virus
NE Peters, BJ Ferguson, M Mazzon, AS Fahy, E Krystofinska, R Arribas-Bosacoma, LH Pearl, H Ren, GL Smith 
PloS Pathogens 9(10): e1003649
2013
Vaccinia virus immune evasion: mechanisms, virulence and immunogenicity
GL Smith, CTO Benfield, CM de Motes, M Mazzon, SWJ Ember, BJ Ferguson, RP Sumner
Journal of General Virology, 94: 2367-2392
2013
A mechanism for induction of a hypoxic response by vaccinia virus
M Mazzon, NE Peters, C Loenarz, EM Krysztofinska, SWJ Ember, BJ Ferguson, GL Smith
Proceedings of the National Academy of Sciences, 110 (30), 12444-12449
2013
Vaccinia virus protein N2 is a nuclear IRF3 inhibitor that promotes virulence 
BJ Ferguson, CTO Benfield, H Ren, VH Lee, GL Frazer, P Strnadova, RP Sumner, GL Smith
Journal of General Virology, 94 (9), 2070-2081
2013
Poxvirus Targeting of E3 Ligase β-TrCP by Molecular Mimicry: A Mechanism to Inhibit NF-κB Activation and Promote Immune Evasion and Virulence
DS Mansur, CM de Motes, L Unterholzner, RP Sumner, BJ Ferguson, H Ren, P Strnadova, AG Bowie, GL Smith
PLoS pathogens 9 (2), e1003183
2013
Vaccinia virus protein C4 inhibits NF-κB activation and promotes virus virulence
SWJ Ember, H Ren, BJ Ferguson, GL Smith
Journal of General Virology 93 (Pt 10), 2098-2108
2012
DNA-PK is a DNA sensor for IRF-3-dependent innate immunity
BJ Ferguson, DS Mansur, NE Peters, H Ren, GL Smith
eLife Sciences 1 e00047
2012