Dr Ian Humphreys
Wellcome Trust Senior Research Fellow. Persistent and Resistant Infections Theme Lead, Systems Immunity Research Institute
Mae'r cynnwys hwn ar gael yn Saesneg yn unig.
I am a Reader and Wellcome Trust Senior Research Fellow in Basic Biomedical Sciences within the Division of Infection & Immunity, School of Medicine. I am theme lead for 'Infection' within the Division. I am also Theme Lead for 'Persistent and Resistent Infections' within the Systems Immunity University Research Institute.
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
Cardiff University, UK:
2007-Present: Current position - Wellcome Trust Senior Research Fellow in Basic Biomedical Science/Reader studying regulation of antiviral immunity.
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
2002: 3rd Prize, Promega National Young Immunologist of the Year
2002: Marshall Scholarship for outstanding Ph.D in biomedical research
British Society of Immunology (BSI)
International Cytokine Society (ICS)
Society of General Microbiology
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.
Recent Invited Talks:
World CMV Meeting/10th Year Anniversary Lecture, Center for Proteomics (Rijeka, Croatia)
University of Pennsylvania (Philadelphia, USA)
MedImmune Inc (Gaithersburg USA)
Institute of Infection, Immunity and Inflammation, University of Glasgow
Department of Pathology, University of Cambridge
Weatherall Institute of Molecular Medicine, University of Oxford
Society of General Microbiology, Liverpool
“Virtual Virology” London Virology Lecture Series (UCL), University College London
International Cytokine Society “Cytokine” Meeting (Bamberg, Germany)
University of Manchester,
Imperial College London
Roslin Institute, Edinburgh
British Society of Immunology – Ita Askonas Celebration (Royal Society, London)
QIMR Berghofer, Brisbane, Australia
Oxford University Clinical Research Unit in Vietnam (OUCRU), (Ho Chi-Minh, Vietnam)
International Cytokine Society “Cytokine” Meeting (Melbourne, Australia)
Sir William Dunn School of Pathology, University of Oxford
Committees and reviewing
Persistent and Resistant Infection Theme Lead, Systems Immunity University Research Institute, Cardiff University
Project License Holder Representative, Biological Standards Committee, Cardiff University
School of Medicine Representative, AWARP Committee
Member, Cardiff Cancer Theme Strategy - Sustainability Task Force
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
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 infection:
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).
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.