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University of Exeter Medical School

Prof Paul Eggleton

Prof Paul Eggleton

Hon Professor of Immunology & Associate Director of Cell Biology UCB Pharma

 P.Eggleton@exeter.ac.uk

 2940

 +44 (0) 1392 722940

 Medical School Building G08

 

Medical School Building, St Luke's Campus, Magdalen Road, Exeter, EX1 2LU, UK


Overview

Paul Eggleton trained in Medical Microbiology, Biochemistry and Immunology at the Royal Free Hospital School of Medicine and Royal College of Surgeons of England under the supervision of Professors Godfrey Smith, Derick Fisher and Neville Crawford. He then conducted post-doctoral research in neutrophil physiology with Professor Alfred Tauber in Boston, USA (1992-94), before joining the MRC Immunochemistry Unit, Oxford (1994-2002), where he conducted his own research in innate immunity (C1q and collectins) under the guidance of Professor Ken Reid FRS.

Dr Eggleton‘s research interest focuses on the understanding of innate and adaptive immunity in the pathology of autoimmune and neurodegenerative diseases (systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis) and more recently, cancer, with a special interest in the role of endoplasmic reticulum chaperone proteins (calreticulin/calnexin).

Dr Eggleton has made important contributions to medical research through his research in characterizing the immune function of the collectin molecules (SP-A and SP-D) and complement proteins (e.g. C1q). He contributed to the discovery of the lectin pathway of complement activation, which has had far reaching implications how human immunity deals with microbial infections. He is also known for his work shown that endoplasmic reticulum (ER) chaperones – e.g. calreticulin have extracellular immune modulating functions. This has led to a whole new avenue of research into the role of calreticulin in the cell death of cancers and the ability of parasites to avoid immune detection. His recent work has contributed to the discovery of a subset of CD20+, T-cell that appear to have a role in many human pathological processes. In addition, his work on post-translational modification of host proteins by oxidative stress and epigenetic/microbial influences has provided insight as to how autoantibodies are generated in autoimmune disease as well explaining how such autoantibodies are implicated in both pathology and as early diagnostic markers of disease.

His current research with clinical colleagues in Tyne & Wear, Cornwall and Oxford have identified certain lung diseases act as an early trigger for inducing rheumatoid arthritis. 

Dr Eggleton was the academic lead for immunology for the University of Exeter Medical School  (2008-2017) where he was responsible for the taught course curriculum for the medical school students - years 1 to 5. 

Dr Eggleton is an Honorary Professor of Immunology at the University of Exeter Medical School and was Visiting Professor at the University of Edmonton, Alberta, Canada, where he works with Professor Marek Michalak and his team in the Department of Biochemistry, investigating the role of chaperones in multiple sclerosis  and tumour immunology. Together they have recently discovered that certain chaperone proteins are implicatated in regulating neuroinflammation processes in the brain. Dr Eggleton is currently Associate Director of Cell Biology at UCB Pharma in the New Medicines Division of the company - http://www.ucbpharma.co.uk/home

Current Industrial Neuroinflammation Interests (2017 onwards).

Directing a neuroinflammation group at UCB Pharma. Investigating a number of druggable CNS pathways within the company with industrial and academic partners. 

Qualifications

  • 1979–1983: Plymouth University. Plymouth, Devon, England.
    (A) Higher National Diploma in Applied Biology.
    (B) B.Sc. Hons. Biological Sciences – Upper second class (2.i).
  • 1985–1987: University College London -Royal Free Hospital School of Medicine.
    M.Phil. Medical Microbiology
    Thesis title: Rapid techniques for the measurement of non-–specific host responses to bacterial infection.
  • 1987–1991: University College London - Royal College of Surgeons of England & Royal Free Hospital School of Medicine.
    Ph.D. Biochemistry
    Thesis title: Studies of subpopulation heterogeneity in the circulating neutrophil pool.

Career

UCB Pharma 2017 onwards

  • Assoc Director UCB Pharma 

University of Exeter Medical School. UK - 2002-2017

  • April 2017-onwards. Hon Professor of Immunology.
  • Nov 2002 - March 2017. Senior lecturer in Immunology. Institute of Biomedical and Clinical Science. 
  • 2009-2012 - Elected Member of University Senate

University of Oxford, UK - 1994-2002

June 1994–August 2002. MRC Immunochemistry Unit, Dept. Biochemistry. South Parks Road. Oxford OX1 3QU.

1994-2002 Position: Research Fellow. (Personal fellowships funded by MRC and ARC)

  • Laboratory Host: Professor KBM Reid FRS. Project A: Structural and functional characterisation of calreticulin in human leucocytes in relation to autoimmune disease Project B: Role of lung surfactant proteins in innate immunity.

1996-2002. Position: Senior Department Teaching Associate.

  • Responsible for designing and managing the first taught D.Phil. course in Biochemistry at the University of Oxford.

1999-2002. Position: University Research Lecturer and Member of congregation, University of Oxford.

Boston University, USA - 1992-1994.

March 1992-May 1994 Department of Pathology, School of Medicine.

  • Position; Research Fellow.
  • Laboratory host: Professor Alfred. I. Tauber. Project: Characterisation of C1q receptors on human neutrophils.

Royal College of Surgeons of England, London, UK - .1989-1992

1989–92. Department of Biochemistry, Hunterian Institute,

  • Position: Research Associate. (ARC – funded).
  • Laboratory host: Professor Neville Crawford. Project: Subpopulation heterogeneity in the circulating neutrophil pool: implications for functional expression in the inflammatory response.

Royal Free Hospital School of Medicine, London UK - 1983-87.

1983–87. Department of Medical Microbiology.

  • Position; Research Assistant. (NETRHA - funded)
  • Laboratory host: Dr. G.W. Smith. Project: Rapid detection assays of host response to bacterial disease.

Links

Research group links

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Research

Research interests

Dr Eggleton‘s research interest focuses on the understanding of innate and adaptive immunity in the pathology of autoimmune disease (systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis) and more recently, cancer, with a special interest in the role of endoplasmic reticulum chaperone proteins (calreticulin/calnexin).

Dr Eggleton has made important contributions to medical research through his research in characterizing the immune function of the collectin molecules (SP-A and SP-D) and complement proteins (e.g. C1q). He contributed to the discovery of the lectin pathway of complement activation, which has had far reaching implications as to how human immunity deals with microbial infections. He is also known for his work shown that endoplasmic reticulum (ER) chaperones – e.g. calreticulin have extracellular immune modulating functions. This has led to a whole new avenue of research into the role of calreticulin in the cell death of cancers and the ability of parasites to avoid immune detection. His recent work has contributed to the discovery of a subset of CD20+, T-lymphocytes that appear to have a role in many human pathological processes. In addition, his work on post-translational modification of host proteins by oxidative stress and epigenetic/microbial influences has provided insight as to how autoantibodies are generated in autoimmune disease as well explaining how such autoantibodies are implicated in both pathology and as early diagnostic markers of disease of both systemic lupus erythematosus and rheumatoid arthritis. 

Research projects

  • Development of cancer immunotherapeutics (Eggleton, Bremer and Michalak)
  • Extracellular role of calreticulin in immunity (Eggleton, Bremer and Michalak)
  • T cell pathology in MS (Eggleton, Bremer, Engelhardt, Gutowski and Michalak)
  • Triggers of rheumatoid arthritis (Eggleton, Hutchinson, Perry and Murphy)
  • Development of new medicines (UCB Pharma)

Research networks

Current staff - Exeter

  1. Dr Miranda Smallwood - Neuroinflammation (2010-12 and 2017-2019)
  2. Dr Trefa Abdullah (PhD student - Exeter) Investigation into the immune promoting mechanisms of calreticulin for targeted cancer cell death and immunotherapy. Funded by: Higher Committee for Education Development in Iraq. (2015-19)
  3. Dr Daniel Murphy (MD student – Exeter) (2016-18) Investigation into cadmium-induced citrullinated protein production as a driver of systemic inflammation in rheumatoid arthritis
  4. Dr Janet Holley (Research associate and consultant neuroscientist) Immune pathology of multiple sclerosis (2014-2018)
  5. Alexander Clark (Research Assistant and PhD student) Lung disease and autoimmunity (2015-2019)
  6. Dr Lucy Moore - Hon Research Fellow  Hyperbaric oxygen as a treatment for multiple sclerosis (2017-20)

Research grants

  • 2016 Cornwall Arthritis Trust.
    Money for part funding of PhD studentship
  • 2014 Cornwall Arthritis Trust.
    Genotyping of rheumatoid arthritis patients for risk alleles
  • 2014 HCED in Iraq PhD Studentship
    Investigation into the immune promoting mechanisms of calreticulin for targeted cancer cell death and Immunotherapy
  • 2014 Northcott Devon Medical Foundation
    Consumables for rheumatoid arthritis research
  • 2014 Royal Devon & Exeter Foundation Trust
    Multiple Sclerosis research grant
  • 2012 Alberta Innovates Health Solution
    Travel Fellowship
  • 2012 Marie Curie Fellowship
    Characterization of CD20+ T-cells in healthy volunteers, ovarian cancer patients and patients with rheumatoid arthritis
  • 0 Multiple Sclerosis Society
    The role of calnexin in T-cell trafficking across the blood-brain barrier in vitro and in vivo
  • 0 Medical Research Council
    Development of novel bi-specific antibody-based fusion proteins to inhibit and kill autoreactive T-cells prior to them crossing the blood brain barrier
  • 0 Alberta Innovates Health Solution
    Exploring the multi-functional anti-tumor activity of calreticulin for targeted ovarian cancer therapy
  • 0 Alberta Innovates Health Solution
    Design of a new immune boosting strategy for ovarian cancer
  • 0 Horizon 2020 Innovative Training Networks (ITN)
    Innovative Training Networks (ITN) Call: H2020-MSCA-ITN-2015 Entitled: An Integrated Network for Exploitation of the Central Role of the Endoplasmic Reticulum for immunotherapy of human disease
  • 0 European Research Council
    European research Council award for Professor Michalak (University of Alberta) and Dr Eggleton to conduct international neurology research
  • 0 Arthritis Research UK
    ARUK PhD studentship

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External Engagement and Impact

Committee/panel activities

  • King Faisal International Prize in Medicine committee (2015-17)
  • Member of European Academy of Tumour Immunology (EATI)
  • Northcott Devon Medical Foundation (2004-2017)

External Examiner Positions

PhD/D.Phil/MD External examiner

  • Univ. of Oxford (UK) 2002 
  • Univ. of Southampton (UK) 2001
  • Univ. of Wales, Cardiff (UK), 2003 
  • Gwangju Institute of Science & Technology, Dukgyu Lee (South Korea) 2007
  • Univ. of Bath, Madelynn Chan (UK) 2011
  • Univ. of Alberta, Joanna Jung (Canada) 2011,
  • Univ. of Groningen, Marco de Bruyn (Netherlands) 2013 ,
  • Univ. of Groningen, Valerie R Wiersma, 2017 (Netherlands).  

Invited lectures

  • 'Can extracellular calreticulin concentrations and anti-calreticulin antibodies really be predictors of disease?' 12th International CRT workshop. Delphi, Greece,  22 May 2017     
  • 'The role of calreticulin in autoimmunity and cancer. Sheffield University, June 20th 2016
  • 'Galectin-9 levels in bronchiectasis: a possible promoter of immunopathology in rheumatoid arthritis, British Soc Rheumatology, Glasgow SECC, 27th April 2016
  • ‘ER chaperones and disease activity in Rheumatoid Arthritis’ 11th Intl. Calreticulin workshop. New York City, May 8-11th 2015.
  • Breakdown of immune tolerance by post translational modification of host proteins’ American College of Rheumatology/ARHP annual meeting, Boston, Nov 15-19th 2014
  • Put the calreticulin amongst the pulmonaries – a possible trigger for rheumatoid arthritis’, Dept Biochemistry, University of Alberta, Canada, July 4th 2014
  • Development of new cancer therapeutics’ ‘Bridging the Gap’ Immunology Workshop, Exeter University, 29th July 2013.
  • ‘Calreticulin and apoptosis’ – 10th International Calreticulin workshop, Banff, April 2013
  • Identification of Th17 cells in rheumatoid arthritis patients and Th17 cell killing by anti-CD20 biological therapeutics’. Bath Combined Lab meeting.  Bath Institute for Rheumatological Diseases. 15th March 2012.
  • The role of extracellular calreticulin inhibiting FasL-mediated apoptosis in rheumatoid arthritis’ – 9th Intl. Calreticulin workshop, Copenhagen, Denmark 30 August 2011
  • Mechanisms of extracellular calreticulin release and its implications in disease’.- Faculty of Medicine, University of Alberta, Canada 16th Aug 2011
  • Discovery and role of CD20+ Th17 lymphocytes in autoimmune disease’. Controversies in Autoimmunity and Rheumatology meeting. Florence, Italy. March 10th
  •  ‘Dysfunctional apoptosis – a possible way to diagnose lupus nephritis’ Dept. of Medicine, Centre for Rheumatology. University College, London. 18th June 2009.
  •  ‘The role of calreticulin in apoptosis and autoimmunity’ University of Edinburgh Centre for Inflammation Research’. 2nd Oct 2009
  • Chair and speaker ‘Mechanisms of extracellular release of CRT from the ER of cells during oxidative stress and apoptosis’. 8th International Calreticulin workshop. Jan 6-8 2009. Vina del Mar, Chile.
  • ’Dysfunctional apoptosis in SLE: A key to diagnosis’. 3rd Peninsula Connective Tissue Disease Meeting. Dec 10th 2008. Future Inn, Plymouth, Devon
  •  ‘Mechanism of the extracellular release of calreticulin: implications in autoimmune disease’. MRC meeting on C1q. St Anne’s College, Oxford July 23rd 2008.
  •  ‘Recognition and clearance of apoptotic cells by members of the lectin-complement pathway’. Gwangju Institute of Science and Technology. Gwangju, South Korea. May 2007
  •  ‘Role of extracellular calreticulin in health and disease’ Hanyang University, Seoul, South Korea. May 2007 
  •  ‘Autoantibody profiling to identify individuals at risk of systemic lupus erythematosus’. Lupus UK national conference Plymouth, UK. Sept 2007
  • Translocation and extracellular release of calreticulin from the ER of cells during oxidative stress and apoptosis’ 14th Congress of Ca2+-Binding Proteins & Ca2+ Function in Health & Disease.  La Palma, Spain Oct 2007
  • Chair and Speaker  ‘Protein modifications in autoimmunity’ British Society of Rheumatology. Birmingham, UK.  May 2007
  • Chair and speaker at the 7th International Calreticulin workshop. Niagara Falls, Canada. April 2006
  • Plenary Speaker at Symposium entitled ‘Interactions between innate and adaptive immunity’ Aberdeen Immunological Association. British Society for Immunology. Thursday 24th April 2003.

Media Coverage

PUBLIC UNDERSTANDING OF SCIENCE

  • Eggleton P (2007) Lupus: a disease of defective waste disposal, but why is it so difficult to diagnose? Lupus UK ‘News & Views’ issue 82:6-7

http://www.lupusuk.org.uk/component/content/article/14-latest-news-archive/154-lupus-a-disease-of-defective-waste-disposal-but-why-is-it-so-difficult-to-diagnose

  • Eggleton P (2008) Training the new generation of doctors at Peninsula Medical School to interpret laboratory tests useful for the diagnosis of SLE. Lupus UK ‘News & Views’ Issue 85:8

http://www.lupusuk.org.uk/component/content/article/14-latest-news-archive/115-training-new-doctors

  • Researchers Pioneer Kidney Disease Prediction Method (2009)

http://www.sdhct.nhs.uk/aboutus/newsandpublications/pressreleases/2009/091030_kidneydiseaseprediction.php

  • Eggleton P (2010) Can your genes predict the risk of getting SLE? Lupus UK ‘News & Views’ issue 90:6-7

http://www.lupusuk.org.uk/component/content/article/14-latest-news-archive/111-genes-and-sle

  • Eggleton P & colleagues (2017) Breakthrough in multiple sclerosis research as scientists discover possible cause of the disease. Daily Telegraph. 24 APRIL 2017

http://www.telegraph.co.uk/news/2017/04/23/breakthrough-multiple-sclerosis-research-scientists-discover/

  • Eggleton P & colleagues (2017) Major breakthrough in search for cause of MS. The Scotsman. 24 APRIL 2017

BBC Radio

BBC World Service  23rd April  2017 'Newhour' Discussing Multiple sclerosis

BBC Radio Somerset 24th April 2017 Morning news, Discussing Multiple sclerosis

BBC Radio Scotland 24th April 2017 Afternoon news, Discussing Multiple sclerosis

BBC TV

BBC Spotlight TV 24th April 2017, Discussing Multiple sclerosis 

Numerous appearances on live phone-ins to discuss autoimmune disease 

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Teaching

Dr Eggleton was the academic lead for immunology for the University of Exeter Medical School where he was  responsible for the taught course curriculum for the medical school students (2004-17).

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Supervision / Group

Postdoctoral researchers

  • Dr. Janet Holley
  • Dr. Lucy Moore
  • Dr. Daniel Murphy MD student
  • Dr. Elizabeth Perry (MD student)

Postgraduate researchers

  • Trefa Abdullah PhD student
  • Emma Charlton Graduate Student
  • Alexander Clarke PhD Student
  • Lucia Lazzereschi Research Assistant
  • Jonna Petzold Graduate student

Alumni

  • Katalin E. Szabo-Taylor (PhD - Exeter) 2008-2011. Peroxiredoxin 2 and the peroxiredoxin based antioxidant system in rheumatoid arthritis. Funded by PCMD
  • Janet Holley (PhD, Exeter) 2005-2009 - Brain scarring, vascular changes and oxidative stress in multiple sclerosis. Funded by Institute of Biomedical and Clinical Science (PMS)
  • Deborah J Shaw (PhD, Exeter) 2005-2008- Characterisation of the interaction between the Ewing Sarcoma protein (EWS) and the Survival Motor Neurone protein (SMN). Funded by Andrews Buddies (Fight SMA, USA) and the Institute of Biomedical and Clinical Science (PMS)
  • Steven Johnson (D.Phil, Oxford) 1997-2001 Characterisation of the structure and pathological roles of human calreticulin. Funded by MRC
  • Courtney Kang (D.Phil, Oxford) 2000-2003 Characterisation of the scavenger receptor, cysteine-rich domain-containing molecule gp340 - Funded by MRC
  • Alexandra Kendall (PhD, Exeter) 2007-2010 - Hyperbaric oxygen alters neutrophil and endothelial cell function in chronic wounds. Funded by DDRC
  • Francis L Shaw (PhD, Exeter) 2004-2007 - The effects of hyperbaric oxygen on platelet physiology. Funded DDRC
  • Leonora Leigh (D.Phil, Oxford). 1996-8 Characterisation and function of the C1q & gC1q receptor. Funded by MRC UK
  • Lesley Maskell (PhD, Exeter) 2004-2008 - An in vitro investigation into the processes involved in angiogenesis, astrocytic changes and boundary formation in brain metastases
  • Emma Murray (D.Phil, Oxford) 1998-2001 - Roles of lung surfactant proteins SP-A and SP-D in innate immunity and Allergy. Funded by MRC
  • Wendy Roake (D.Phil, Oxford) 2000-2003 - Role of surfactant protein A and D in apoptotic cell recognition Funded by MRC
  • Brent Ryan (PhD, Exeter) 2006-2010 - The effect of Oxidative post-translational modifications to C1q on its antigenicity and function, in relation to the pathogenesis of systemic lupus erythematosus Funded ARCUK
  • Dr. Miranda Smallwood
  • Thomas Vorup-Jensen (M.Sc, Oxford/Aarhus, Denmark) 1998 - Characterisation of the human mannan associated serine proteases (MASPs)

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