Principal Investigators in Oxford
Professor Tao DongProfessor of Immunology, Director (Oxford) CAMS Oxford Institute.
The main objective of my group’s research is to focus on the functional aspects of the antigen specific T cells and studying the factors affecting T cells in controlling virus infection and cancer development.
For important human infections, cancer development and the course of disease is influenced mainly by the T cell response - while a robust and appropriate T cell response is beneficial to the host, a weak or inappropriate response can be ineffective or even have a detrimental effect. Numerous factors influence the quality of the T cell response to viral infections, predominant among them being the microenvironment of the infection site, the type of cells infected and the variability of the virus.
To define the impact of IFTIM3 genetic variation on Influenza, and other virus infection, immune responses and disease outcome
To study the Viral OncoProtein(VOP) and Tumor Specific Protein(TSP) specific T cell responses in virus associated cancer (I.e. HBV/HCC; EBV/NPC and HPV/CC)
To identify the factors determining functional avidity and anti-viral/cancer efficacy of antigen specific T cells in cancer micro-environment.
Mr Darren Nash
Associate Head of Department, NDM Oxford Subsidiary Company Non-Executive Director, Strategic and Finance Director, CAMS Oxford Institute
Darren is the Associate Head of Department for academic support, finance and human resources at the Nuffield Department of Medicine. In this role he is responsible for all business management functions and all non-academic staff in the Department, including major activities and units in Oxford, Kenya, Vietnam, Thailand and China.
He is also a Director of three university subsidiary companies. He has an MBA from Oxford’s Said Business School, and combined with 25 years experience in this global research environment provides support and training to partner organisations to facilitate research.
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Professor Richard Cornall
Nuffield Professor of Clinical Medicine and Head of Department, Professor of Immunology
Our aim is to understand how the immune system is formed and regulated and the causes of autoimmunity, particularly the systemic autoimmune diseases, and the development and selection of B cells. Adverse immunological reactions to self and foreign antigens that lead to autoimmune or inflammatory disease place a major economic and social burden on world health and individual quality of life. We are also interested in how people differ in their inherited susceptibility to these diseases and why these differences are sustained in human populations by natural selection. Advances in this area will have a large and impact on the management of human disease.
Our strategy involves research programmes in basic biology and in clinical medicine. In the first, we use transgenic models to investigate how lymphocytes function in health and in human disease and how our genes encode susceptibility to autoimmunity and immunodeficiency. In the second, which is a collaboration with Professor Simon Davis, we are developing ways to change the function of lymphocytes, turning them on in cancer and off during inflammation or autoimmunity.
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PROFESSOR MICHAEL DUSTIN
Kennedy trust Professor of Molecular Immunology
Prof. Dustin has a B.A. in Biology from Boston University (1984) and a Ph.D. in Cell and Developmental Biology from Harvard University (1990). Dr. Dustin led his own group at the Department of Pathology at Washington University School of Medicine under Steve Teitelbaum and Emil Unanue from 1993 to 2000. While at Wash U, he led a collaborative group in discovering requirements for the T cell immunological synapse with Andrey Shaw, Paul Allen, Mark Davis (Stanford) and Emil Unanue.
Continuation of work on the immunological synapse led to a basic description of the supramolecular assemblies that make up the mature immunological synapse. Specialized functions of the immunological synapse in cytotoxic T cells and regulatory T cells were also explored.
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Professor Tim Elliott
Kidani Professor of Immuno-oncology and Fellow of Oriel College
Tim Elliott is a world leader in the field of antigen presentation and T cell biology and has incorporated discoveries in the areas of antigen processing, T cell regulation and immunodominance into the development of new cancer immunotherapies. He is a Fellow of the Royal Society for Biology and Fellow of the Academy of Medical Sciences; founding Editor-in-Chief of the journal Immunotherapy Advances published by the British Society for Immunology; and chaired the Cancer Research UK Cancer Immunology expert review committee.
Professor Elliott was appointed to the Kidani Chair of Immuno-Oncology at the University of Oxford in 2020.
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Dr Ricardo Fernandes
Group Leader - Cancer Immunology
The main objective of our research group is to identify key functional aspects affecting anti-tumor responses by T cells. To do this, we use protein engineering, guided by structural and signaling information, to generate novel molecules that allow us to explore and interrogate key aspects of receptor signaling and T cell function. We are currently focusing our efforts in developing molecules to overcome “inhibitory” signaling by immune checkpoint receptors and to enhance signaling by the T-cell receptor.
Ricardo Fernandes recently joined CAMS Oxford Institute coming from Stanford where he developed novel molecules to effectively shut down signaling by immune receptors such as PD-1.
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Professor Roman Fischer
Associate Professor and Head of Discovery Proteomics Facility
In the Discovery Proteomics Facility of the Target Discovery Institute we provide advice in experimental design, sample preparation, sample analysis with state-of-the-art LCMS workflows and data analysis to researchers from Oxford University and national and international collaborators. We routinely use label-free quantitation, SILAC, TMT, SWATH and other methodologies on diverse samples (i.e. cells, tissues, immuno precipitates et al.) and have developed sample preparation techniques to access the deep proteome form little sample amounts using instrumentation such as Orbitrap Fusion Lumos or TimsTOF Pro.
My own interests evolve around clinical proteomics and applications for the spatial characterisation of the proteome in biological structures such as tissues and tumours. In addition, I am developing methodologies for the proteome characterisation of clinical cohort samples at high-throughput.
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Professor Dame Sarah Gilbert
Saïd Professorship of Vaccinology (FMedSci), Dame Commander of the Most Excellent Order of the British Empire (DBE), for services to Science and Public Health.
A post in Prof Gilbert’s lab is funded by the Chinese Academy of Medical Sciences to work in collaboration with Prof Tao Dong’s lab. The research topic is the processing and presentation of T cell epitopes from nucleic acid-based vaccines, to include adenoviral vectored vaccines and RNA vaccines. The work will assess alternative antigen designs for use in the vaccine technologies and assess the effect on T cell epitope processing and presentation. This will inform the development of vaccines against outbreak pathogens which may be further developed within the Pandemic Sciences Institute
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Professor Ling-Pei Ho
Associate Professor Respiratory Medicine
We are interested in how immunological responses impact on mechanisms of lung injury and repair. The projects are divided into mechanistic and translational studies. The mechanistic studies question how innate immune cells like iNKT cells, MDSCs and monocyte-macrophage lineage impact on outcome in severe influenza virus infection and progression of lung fibrosis. These studies inform, drive and allow us to test mechanistic hypotheses in/from our human work.
In the translational space, our focus is on new or improved therapy for lung fibrosis. Our diseases of interest are idiopathic pulmonary fibrosis (IPF) and fibrotic sarcoidosis, and we target the interface between cellular immunology, disease mechanisms and early clinical trials.
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Professor E. Yvonne Jones
Professor of Protein Crystallography (FRS), Joint Head Division of Structural Biology, NDM
Yvonne Jones is Director of the Cancer Research UK Receptor Structure Research Group which is focused on the structural biology of extracellular recognition and signalling complexes. The group's core techniques include protein crystallography and, increasingly, cryo electron microscopy, which are used to generate high resolution structural information. Importantly, studies using these techniques are integrated with advanced light microscopy and cryo electron tomography, as well as cell-based functional studies, to probe molecular mechanisms at the cell surface.
The group's research addresses fundamental questions about cell-cell signalling systems of importance to human health. The work ties into an extensive network of interdisciplinary local and international collaborations with the ultimate aim of learning how to manipulate these signalling systems for the design of new clinical therapies. Current projects within the group focus on signalling systems of importance in developmental biology.
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Professor Benedikt Kessler
Professor of Biochemistry and Mass Spectrometry
We intend to analyze a particular subset of the deubiquitylating enzyme family, containing an ovarian tumor domain (OTU). This conserved motif encodes for a potential cysteine protease, and is conserved throughout evolution. However, the function of this class of proteins is largely unknown. An approach based on a tandem affinity purification strategy will be established to determine protein interaction partners. A proteomics screen for protease substrate discovery will be established to identify substrates and provide entry points for genetic and biochemical analyses of their function.
Our studies indicate a central role for OTUs, in particular OTUB1, in regulating cell invasion and morphology by modulating the stability of small GTPases. The impact of these molecular interactions are studied within the context of host-pathogen interactions and tumourigenesis.
Professor Julian Knight
Professor of Genomic Medicine, Deputy Director Graduate Studies
My research aims to understand how genetic variation impacts genes critical to mounting an appropriate immune response and may contribute to susceptibility to infectious, inflammatory and autoimmune diseases. There is a wide spectrum of genetic variation modulating inter-individual differences in immune response with functional consequences ranging from severe primary immunodeficiency disorders to risk of multifactorial traits involving inflammation and immunity. Our recent discovery that non-coding regulatory variants are major drivers of diversity in the immune response transcriptome identifies an important mechanism for this.
We have established translational programmes in the genomics of sepsis as part of the Genomic Advances in Sepsis study and in ankylosing spondylitis. We aim to promote use of genomics for drug target identification and validation, public engagement with genomics and implementation of genomic medicine in the clinic through education, training and a multidisciplinary approach.
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Professor Marian Knight
Professor of Maternal and Child Population Health
Marian Knight is Professor of Maternal and Child Population Health at the National Perinatal Epidemiology Unit. She trained initially in obstetrics and neonatology, completing a DPhil investigating the pathogenesis of pre-eclampsia, before becoming interested in epidemiology and population health. She therefore undertook specialty training in public health, becoming a Fellow of the Faculty of Public Health in 2006. She is an Honorary Consultant in Public Health with Public Health England. Her work focuses on using national observational studies to address clinical questions concerning rare and severe complications of pregnancy and early life. She also leads the MBRRACE-UK national confidential enquiries into maternal morbidity and mortality.
Professor Teresa Lambe
Associate Professor and Jenner Investigator
Associate Professor Teresa Lambe is a Principal Investigator at the University of Oxford. Professor Lambe has been involved in immunology research for over fifteen years with extensive knowledge in the assessment of naturally acquired and post-vaccination immune responses.
Professor Lambe’s research programme focuses on developing innovative vaccines against emerging and outbreak pathogens. Outside of her most recent work on the ChAdOx1 nCoV-19 (AZD1222) vaccine, her group have progressed novel vaccine development against lethal haemorrhagic viral diseases such as Ebolavirus, Lassa fever virus and Crimean-Congo haemorrhagic fever. This experience proved to be a dry-run for her recent work developing a vaccine against SARS-CoV-2. As well as her role in the initial design of the ChAdOx1 nCoV-19 vaccine and leading the pre-clinical testing programme, Professor Lambe’s group are leading critical laboratory studies evaluating the antibody response post-vaccination..
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Professor Xin Lu
Professor of Cancer Biology, Director Ludwig Institute for Cancer Research Oxford Branch
The main goal of our research is to identify molecular mechanisms that control cellular plasticity and suppress tumour growth. Cells are able to change their characteristics and cell fate in response to external signals. This ability to change – cellular plasticity – underlies cancer initiation, metastasis and resistance to therapy. We are particularly interested in ‘guardians’ of plasticity in epithelial cells, from which over 80% of human tumours originate. We have a long-standing interest in the tumour suppressor p53 and the ASPP family of proteins (Apoptosis-Stimulating Protein of p53; Ankyrin repeats, SH3 domain and Prolin rich sequence containing proteins), which have several roles including regulation of p53.
Our current areas of interest include: understanding how selective transcription is controls cell fate; identifying regulators of cellular plasticity in upper gastrointestinal cancer initiation and metastasis (particularly oesophageal cancer and gastric cancer); and understanding the influence of infection on cell plasticity and cancer (particularly Helicobacter pylori and Epstein Barr Virus (EBV) infection).
Professor Jane McKeating
Professor of Molecular Biology
Our research focuses on understanding early infection events that define cellular and tissue tropism of clinically important viruses. Preventing viral induced disease begins with an understanding of the host factors that define susceptibility to infection.
We recently discovered that the low oxygen environment naturally found in the liver enhances HBV and HCV replication and this is mediated by hypoxia inducible transcription factors (HIFs). Inhibiting HIFs or suppressing their expression limits virus infection, highlighting new therapeutic approaches.
Studies in our laboratory show that hypoxia limits HIV transcription and HIF-stabilizing drugs potentiate viral reactivation from latent sites of infection. Understanding the role of hypoxia induced signalling and metabolic effects on HIV transcription and latency will inform the development of new ‘curative strategies’.
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Professor Sir Andrew McMichael
Emeritus Professor of Immunology (FRS)
Andrew McMichael’s group works on HIV vaccine development. In collaboration with Louis Picker, OHSU, he is working on the MHC-E restricted T cell responses that can clear acute SIV infection in some monkeys. This relates to his work with Veronique Braud in 1998 when they showed how HLA-E presents a particular peptide to NKG2/CD94 to regulate natural killer cells. When primed by a rhesus CMV vaccine recombinant for SIV genes or by mycobacteria, HLA-E can also present a range of epitope peptides to CD8 T cells. In collaboration with Geraldine Gillespie and Yvonne Jones, Lucy Walters has determined the structures of HLA-E bound to a set of epitope peptides. These structures reveal how HLA-E can bind peptides with very diverse sequences eliciting the exceptionally broad T cell responses that can clear SIV.
Together with Professor Persephone Borrow his group are also exploring the relationships between human T follicular helper cells and other CD4 T cells in blood and tonsils. He is asking whether microbiome antigens can prime naïve CD4 T cells in humans and establish a repertoire of pre-immune cross reactive memory cells that dominate primary T cell responses to vaccines.
His work is highly relevant to pathogen immunity and he has strong links to Chinese colleagues at the CTI, CAMS, China CDC and You’an Hospital.
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Professor Graham Ogg
Professor of Dermatology
Skin and mucosae frequently represent the first point of contact with pathogens and allergens, yet we still know relatively little of the role of the surface immune system in clearing such challenges. This is crucially important in understanding the mechanisms of skin diseases and related diseases, and for optimising approaches to cutaneous drug and vaccine delivery.
The aim of the group is therefore to understand, at the molecular and cellular level, the role of human cutaneous immune responses in mechanisms of disease, treatment and vaccination. As well as contributing to an understanding of disease pathogenesis, we aim to translate our findings to changes in clinical practice.
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PROFESSOR Beth Psaila
Associate Professor of Haematology
Beth Psaila’s group apply state-of-the-art approaches to study normal and malignant megakaryocyte biology and bone marrow fibrosis, to identify new targets for therapy for patients with myeloproliferative neoplasms. We are also interested in the role of platelets as biomarkers for early cancer detection.
Beth is an Associate Professor of Haematology and Group Leader at the MRC Weatherall Institute of Molecular Medicine. She is also a haematology consultant, specialising in the care of patients with myeloproliferative neoplasms, and a Senior Fellow in Medicine at New College Oxford.
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Professor NAJIB M RAHMAN
Professor of Respiratory Medicine, Director, Oxford Respiratory Trials Unit (ORTU), Deputy National Lead for Respiratory Research, NIHR Clinical Research Network (BM BCh MA (oxon) MSc (LSHTM) FRCP DPhil)
My research group addresses key issues in the assessment and management of patients with pleural disease, which is common, affecting over 300,000 patients every year. The evidence base in pleural disease has historically been modest , and our understanding of underlying disease mechanisms limited.
Our goal is to use translational and observational studies to understand underlying mechanisms, and to deliver well designed robust clinical trials which change practice. My group has expertise in randomised multicenter clinical trials of new agents and devices, and in using derived clinical samples to conduct translational work.
Our previous work has identified a novel treatment for pleural infection (NEJM 2011) and derived a validated risk score (ERJ 2020), defined optimal management in malignant pleural effusion (JAMA 2012, JAMA 2015, JAMA 2020, NEJM 2019), and identified novel ambulatory treatment in pneumothorax (Lancet 2020).
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Professor Gavin Screaton
Professor of Immunology, Head Medical Sciences Division
His research has ranged from control of RNA processing and apoptosis to immunology. The current focus of his laboratory revolves around the immunology of infectious diseases, especially dengue haemorrhagic fever and Zika virus. This work is funded by the MRC and the Wellcome Trust and involves active research collaborations in South East Asia.
He is a Fellow of the Academy of Medical Sciences, a Fellow of the Royal College of Physicians, a member of the Association of Physicians, and was made a Founder Senior Investigator in the National Institute for Health Research. He sits on the MRC Strategy Board.
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Professor Geoff Smith
Professor of Pathology
Professor Smith's research focusses on the understanding of poxviruses. Poxviruses are large DNA viruses that replicate in the cytoplasm and encode many proteins that aid evasion of host innate immunity. The most infamous poxvirus is variola virus that caused smallpox, a disease declared eradicated in 1980 by the WHO following widespread vaccination with the related orthopoxvirus, vaccinia virus (VACV). Thereafter, poxviruses have not caused major outbreaks in humans until a global monkeypox virus epidemic in 2022.
To improve the safety and immunogenicity of poxvirus-based vaccines and to better understand how viruses cause disease and escape the host response to infection, our group is studying the mechanisms by which orthopoxviruses suppress innate immunity. Two parallel approaches are used.
Professor Alison Simmons
Director of the MRC Human Immunology Unit, Professor of Gastroenterology NIHR Research Professor
We use large-scale molecular assays to define features of innate immune signaling pathways that are dysregulated in human disease. Definition of such molecular pathways often highlights strategies to reverse these defects. We have applied these techniques to study of various innate immune receptors including NOD2, a receptor that is defective in western Crohn’s disease. In work with the CTI we will extend these studies to explore innate signaling defects present in human liver disease that contribute to disease progression and development of hepatocellular carcinoma. This will enable molecular screens to define targets for novel therapeutic design in these conditions.
Current Research Themes: Mechanisms of pattern recognition receptor function in health and inflammation; Molecular redefinition of human intestinal cells in health and digestive disease; Improving the treatment and management of Inflammatory Bowel Disease.
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Professor Sir David Stuart
Professor of Structural Biology (FRS), Director of the Division of Structural Biology
Viruses are attractive targets for study at the molecular level, since they are sufficiently simple that we may hope to achieve a rather complete understanding of their biology. In practice although their genomes are compact they display astonishing diversity, both in structure and function. Our attempts to relate structure to function have benefited from the developments in X-ray crystallographic methods that have brought very complex structures within reach of description in atomic detail. Our targets range from picornaviruses, small ssRNA viruses, which include a number of important animal and human pathogens, to the larger dsRNA viruses. At both ends of this spectrum (from less than 10,000,000 to about 100,000,000 Daltons) we now have representative atomic structures.
Our efforts are particularly focused on virus-receptor interactions and basic puzzles of virus assembly. Our studies here are highly collaborative, with strong links with a number of virologists (P. Mertens and B. Charleston (Pirbright), D. Rowlands (Leeds), P. Roy (London) as well as numerous groups elsewhere in Europe).
Work on cell-surface molecules is largely performed in collaboration with the group of Prof. E.Y. Jones, whose entry describes many of the projects.
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Professor Alain Townsend
Professor of Molecular Immunology (FRS)
Most of my work has been concerned with the presentation of Influenza antigens with class I molecules of the Major Histocompatibility complex. With the recent pandemic this interest continues with a practical extension into the issue of whether heterotypic immunity (between pandemic strains) can be induced in man with live attenuated strains of influenza. We have developed our own design of live attenuated virus called S-FLU, that relies on mutations in the haemagglutinin signal sequence that are permissive for infection but prevent replication of the virus. The advantage of this approach is that all of the viral proteins are expressed in their appropriate context in the lung, and thus can induce a full set of local T and B cell responses.
We are presently investigating the mechanisms of this immunity. As part of a broader interest in human immunity to influenza we are isolating human monoclonal antibodies that neutralise the virus with a view to investigating their potential as therapeutic agents in severe influenza infections. An additional aim for this project is to build a library of neutralising antibody genes that can be used as building blocks in a molecular engineering project to form bi-specific antibodies that can neutralise by two mechanisms at once that may be more effective than reagents with single specificities.
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PROFESSOR Clare Verrill
Associate Professor of Pathology
I am a specialist urological histopathologist with Oxford University with my own research group, the Verrill Pathology Group, focussing on digital pathology, AI and tissue-based research and with active research funding as PI including a prospective AI evaluation study (Articulate Pro). Under my stewardship the NHS Cellular Pathology Laboratory in Oxford is now 100% digital, one of the first few in the UK to achieve this and serving as a real world testing site for AI. I support multiple high-profile clinical trials and research projects and work with industry partners including Philips and Paige. I am internationally recognised in uropathology, most recently for example, co-authoring the testis chapter of the WHO 2022 blue book for genito-urinary malignancies.
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PROFESSOR PEIJUN ZHANG
Professor of Structural Biology and Wellcome Trust Investigator
Our research aims at an integrated, atomistic understanding of human pathogen and host cell interactions in the native biological context by developing and combining novel technologies for high-resolution cryoEM/cryoET, with advanced, complementary methods for biological analysis and computational modeling. The three main areas of my current and future research are 1) Virus infection and host cell interactions, examples include HIV-1 and SARS-CoV-2; 2) Mechanisms of signal transduction and integration in bacterial chemotaxis; and 3)Develop and apply novel technologies in high-resolution cryoEM/cryoET.
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