Professor Ian Humphreys

Professor of Viral Pathogenesis and Lead Co-Director of Systems Immunity Research Institute

: HumphreysIR@cardiff.ac.uk
: +44 29206 87076
: Henry Wellcome Building for Biomedical Research, Room 3F08, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN

I am a Professor of Viral Pathogenesis and Wellcome Trust Senior Research Fellow in Basic Biomedical Sciences within the Division of Infection & Immunity, School of Medicine. My laboratory studies the regulation of immune responses during viral infections. I am also Lead Co-Director of the Systems Immunity University Research Institute and Lead for Infections and Pandemics.

2007

Humphreys, I. R. et al. 2007. OX40 costimulation promotes persistence of cytomegalovirus-specific CD8 T cells: a CD4 dependent mechanism. Journal of Immunology 179, pp. 2195-2202.
Humphreys, I. R., De Trez, C., Kinkade, A., Benedict, C. A., Croft, M. and Ware, C. F. 2007. Cytomegalovirus exploits IL-10-mediated immune regulation in the salivary glands. Journal of Experimental Medicine 204(5), pp. 1217-25. (10.1084/jem.20062424)

2005

Cheung, T. C. et al. 2005. Evolutionarily divergent herpesviruses modulate T cell activation by targeting the herpesvirus entry mediator cosignaling pathway. Proceedings of the National Academy of Sciences 102(47), pp. 13218-13223. (10.1073/pnas.0506172102)
Stewart, G. R. et al. 2005. The stress-responsive chaperone alpha-crystallin 2 is required for pathogenesis of Mycobacterium tuberculosis. Molecular Microbiology 55(4), pp. 1127-1137. (10.1111/j.1365-2958.2004.04450.x)

2004

Hale, C. et al. 2004. Mucosal immunisation of murine neonates using whole cell and acellular Pertussis vaccines. Vaccine 22(27-28), pp. 3595-3602. (10.1016/j.vaccine.2004.03.039)
Hussell, T., Snelgrove, R., Humphreys, I. and Williams, A. E. 2004. Co-stimulation: novel methods for preventing viral-induced lung inflammation. Trends in Molecular Medicine 10(8), pp. 379-386. (10.1016/j.molmed.2004.06.006)

2003

Humphreys, I. R., Walzl, G., Hussell, T. and Hill, S. 2003. A critical role for OX40 in T cell-mediated immunopathology during lung viral infection. Journal of Experimental Medicine 198(8), pp. 1237-42. (10.1084/jem.20030351)
Humphreys, I., Edwards, L. C., Walzl, G., Rae, A. J., Dougan, G., Hill, S. and Hussell, T. 2003. OX40 ligation on activated T cells enhances the control of Cryptococcus neoformans and reduces pulmonary eosinophilia. Journal of Immunology 170(12), pp. 6125-6132. (10.4049/jimmunol.170.12.6125)
Walzl, G., Humphreys, I., Marshall, B. G., Edwards, L. C., Openshaw, P. J., Shaw, R. J. and Hussell, T. 2003. Prior exposure to live Mycobacterium bovis BCG decreases Cryptococcus neoformans-induced lung eosinophilia in a gamma interferon-dependent manner. Infection and Immunity 71(6), pp. 3384-3391. (10.1128/IAI.71.6.3384-3391.2003)

2002

Dearman, R., Filby, A., Humphreys, I. and Kimber, I. 2002. Interleukins 5 and 13 characterize immune responses to respiratory sensitizing acid anhydrides. Journal of Applied Toxicology 22(5), pp. 317-325. (10.1002/jat.865)

2000

Dearman, R., Warbrick, E., Humphreys, I. and Kimber, I. 2000. Characterization in mice of the immunological properties of five allergenic acid anhydrides. Journal of Applied Toxicology 20(3), pp. 221-230. (10.1002/(SICI)1099-1263(200005/06)20:3<221::AID-JAT651>3.0.CO;2-#)

Our laboratory uses in vivo models of viral infection in combination with clinical samples to help us understand the mechanisms that regulate antiviral immunity.

Immune mechanisms that facilitate virus persistence:

Herpesviruses including the beta-herpesvirus human cytomegalovirus (HCMV) cause significant morbidity and mortality. These viruses replicate within and shed from mucosal organs such as the salivary glands. A significant aspect of our research to date has investigated the immune mechanisms that allow virus persistence within mucosal tissues and identify how they suppress antiviral immune responsiveness.

Using the murine cytomegalovirus (mCMV) model of infection, we discovered that production of the immune regulatory cytokine IL-10 by T cells is a hallmark of chronic viral infection (Humphreys et al, J Exp Med, 2007), and IL-10 suppresses antiviral immunity during mucosal viral persistence (Humphreys et al, J Exp Med, 2007) and viral latency (Jones et al, J Immunol, 2010). We have identified that virus-specific T cells in mucosal and non-mucosal tissues in mice and humans secrete IL-10, and identified that T cell production of IL-10, which is triggered by the cytokine IL-27, promotes virus persistence and shedding from the mucosa through suppression of antiviral T cell accumulation (Clement et al, PLoS Pathogens, 2016).

We also discovered that ineffectual antiviral immunity within the mucosa was due, in part, to suboptimal proliferation of mucosal myeloid cells and observed that the inhibitory CD200 receptor (CD200R), expressed by myeloid cells residing within the salivary glands, restricted myeloid cell proliferation triggered by mCMV, and subsequently suppressed anti-viral T cell immunity. This finding suggested that herpesviruses that encode functional homologues of the CD200R ligand might do so to exploit this immune regulatory process. This study also suggested that enhancing myeloid cell proliferation within mucosal tissues improves the induction of mucosal anti-viral T cell responses (Stack et al, PLoS Pathogens, 2015).

Early cytokine-mediated control of virus-induced immune responses:

Our research also studies how early cytokine responses influence antiviral immune responses. We discovered that, despite its suppressive activities, IL-10 promotes NK cell immunity via restriction of activation-induced cell death (Stacey et al, J Immunol, 2011). Further, we identified that the IL-10-related cytokine IL-22 exerts tissue-specific control of mCMV replication. We found that neutrophils induced by IL-22 act as efficient antiviral effector cells that restrict mCMV replication during acute infections in certain tissues (lung and liver).

We are also interested in how early immune signals could be harnessed to improve virus-induced immune responses. We have discovered that the alarmin IL-33 acts early to improve virus-induced T cell responses, demonstrating the possible utility of cytokines as adjuvants in vaccine strategies using viral vectors (Mclaren et al, J Immunol, 2019 - Top 10 most-read papers 2019).

Regulation of Viral Pathogenesis:

Our laboratory also aims to identify what mechanisms regulate cytokine-driven viral pathogenesis. In studies facilitated by an extensive and on-going collaboration with the Wellcome Trust Sanger Institute, we discovered that an intrinsic immune protein, interferon-induced transmembrane protein 3 (Ifitm3), restricts cytokine-mediated viral pathogenesis independently of direct antiviral control that is typically considered the primary function of intrinsic immune proteins (Stacey et al, J Clin Invest, 2017). IL-6, a cytokine that we helped identify as a central inflammatory mediator of fibrosis (Fielding et al, Immunity, 2014), exacerbated mCMV-induced inflammation despite also being required for the generation of cellular antiviral immune responses. These data highlighted that early control of pro-inflammatory cytokines is crucial for balancing antiviral immunity and viral-induced immune pathogenesis. A minor allele of Ifitm3, which is implicated in reduced Ifitm3 function, is a risk factor for viral pathogenesis in humans. Thus, this finding highlights the potential importance of anti-inflammatory therapies in personalized treatment of viral pathogenesis in genetically susceptible individuals. We have developed human myeloid cell models using stem cell technology that enable genetic studies of the cellular factors that influence virus-induced inflammatory responses (Forbester et al, J Vir, 2020).

COVID-19

I am Cardiff Lead in the UK-COVID19 Immunology Consoortium (UK-CIC), studying the role of the immune response in SARS-CoV-2 infection, with specific projects in this area including identification of markers predictive of COVID-19 outcome.

ME3030 Microbial pathogenesis

ME3045 Advanced Immunology

Virology Tutor, C21

SSC Year 1 Tutor – Literature Projects

SSC Year 2 – Laboratory Placement Supervisor

Small Group (PCS) Tutor

Academic Mentoring

Education and Qualifications:

2004: PhD in Biochemistry, Centre of Molecular Microbiology and Infection, Imperial College London
2000: BSc in Biological Sciences with Virology, University of Warwick

Career Overview:

Cardiff University, UK (2007-Present):

2021-Present: Director, Systems Immunity University Research Institute
2018-Present: Professor of Viral Pathogenesis
2012-Present: Wellcome Trust Senior Research Fellow
2007-2012: Wellcome Trust Research Career Development Fellow

La Jolla Institute for Allergy and Immunology, San Diego USA:

2000-2004: Postdoctoral Researcher

Imperial College London, UK:

2004: Postdoctoral Researcher
2000-2004: PhD Student

Honours and awards

Major Honours and Distinctions:

2017: Awarded a Renewal of a Wellcome Trust Senior Fellowship in Basic Biomedical Science
2016: Appointed Member of the British Society of Immunology Congress Committee
2014: Appointed Member of the Wellcome Trust Basic Science Interview Committee
2013: Appointed as Honorary Faculty at the Wellcome Trust Sanger Institute
2012: Wellcome Trust Senior Fellowship in Basic Biomedical Science
2007: Wellcome Trust Research Career Development Fellowship

Professional memberships

British Society of Immunology (BSI)
International Cytokine Society (ICS)
Society of General Microbiology

Academic positions

La Jolla Institute for Allergy and Immunology, San Diego USA:

2004-2006: Postdoctoral Scientist working with Professors Carl Ware and Mick Croft investigating the role of TNF and TNF receptor family members in T cell responses to cytomegalovirus infection.

Imperial College London, UK:

2004: Postdoctoral scientist working with Professor Douglas Young studying the dissemination of mycobacteria in vivo.

Committees and reviewing

2020: Immune System in Health and Disease Expert Review Group, Wellcome Trust
2016-2020: British Society for Immunology, Congress Committee
2014-2019: Wellcome Trust Basic Science Interview Committee

I am a member of the Welsh Government International Intelligence group, providing insight into the COVID-19 pandemic. In response to the COVID-19 pandemic, I have been engaging with numerous companies regarding SARS-CoV-2 research projects.

I have 18 years' experience of undertaking public engagement. I run a series of activities in primary schools including microscopic analysis of immune cells, performing experiments and using Lego to teach people of all ages about complex immunological concepts in a simple manner. My laboratory also coordinates the immunology section of the highly successful Science in Health Live! event promoting biomedical research to A-Level students. Participating students experience the laboratory setting and learn about harnessing the immune system to treat diseases and the different cutting edge technologies utilised in the lab.

Systems Immunity Research Institute showcases recent successes

Professor Ian Humphreys

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