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Ian Humphreys

Professor Ian Humphreys

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

School of Medicine

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

Overview

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.

Publication

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Articles

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Websites

Research

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.

Teaching

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

Biography

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

Engagement

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.