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Professor Donna E Davies BSc, PhD

Professor of Respiratory Cell and Molecular Biology

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Professor Donna Davies is Professor of Respiratory Cell and Molecular Biology, within Medicine at the University of Southampton.

Why do I study lung diseases? The average person takes around 20,000 breaths every day.... imagine fighting for every one of them. That's the reality for 1 person in 7 in the UK who is affected by lung disease

Professor Donna Davies (nee Harrison) was awarded a Personal Chair in Respiratory Cell and Molecular Biology in 2004. She graduated with a first class degree in Biochemistry from the University of Wales and completed her PhD in microbial biochemistry in 1979. She started her post-doctoral studies at the University of Oxford investigating the regulation of insulin secretion and continued this work following the award of an RD Lawrence Fellowship from the British Diabetic Association in 1982. She moved to the CRC Wessex Medical Oncology Unit at the University of Southampton in 1985, before she joined the Respiratory Group through the award of a University of Southampton Senior Research Fellowship in 1998 and then a Readership in 2002.  In 2014, she received the Robert A. Cooke Memorial Medal from the American Academy Of Allergy, Asthma & Immunology. She is a Fellow of the Academy of Medical Sciences (since 2014), a Fellow of the European Respiratory Society (since 2015) and received lifetime membership of the British Association for Lung Research in recognition of her contribution to the BALR and lung research (since 2020). Her H-index is 79 and she has published more than 200 papers with a total of 23233 citations

Professor Davies leads a multidisciplinary group that studies mechanisms of respiratory diseases, especially in areas of unmet medical need such as severe, corticosteroid refractory asthma, virus-induced exacerbations of asthma and COPD, interstitial lung diseases such as idiopathic pulmonary fibrosis (IPF) and, most recently, COVID-19. She has pioneered the use of in vitro models allowing the use of methodologies that could not be used ethically in vivo. The group works closely with respiratory physicians and colleagues within the centre, with other academic centres and industry in the UK, Europe and the USA.

Notable discoveries from her work include demonstration of defective epithelial barrier function in asthma, dissection of the biological function of the asthma susceptibility gene, ADAM33, involvement of the epithelial mesenchymal tropic unit in asthma pathogenesis, dysregulation of collagen nanoarchitecture in IPF and identification of a lesion in innate immune response of asthmatic epithelial cells that may explain why the common cold virus causes exacerbations of asthma. The latter discovery led to a patent for the use of inhaled interferon-beta (IFN-β) for treatment of virus-induced exacerbations of asthma and COPD. To translate this discovery into a potentially new therapy, she co-founded the University of Southampton spin-out company ‘Synairgen’, with Stephen Holgate and Ratko Djukanovic in 2003 and she continues to play an active role in the company. The company has developed inhaled IFN-β and successfully completed phase II trials in asthma and COPD. With the urgency of the COVID19 pandemic, the company redirected its efforts towards testing inhaled  IFN-β  as a treatment for this disease. On 20 July 2020, Synairgen announced positive results from its Phase II double-blind placebo-controlled trial, called SG016, in hospitalised COVID-19 patients.  

Qualifications

BSc, Biochemistry, University of Wales (1975)

PhD, Ribulose 1,5 Bisphosphate Carboxylase from Microorganisms,
University of Wales (1979)

Appointments held

Post-Doctoral Research Associate, Nuffield Dept. of Clinical Biochemistry, University of Oxford (1979-1982)

R.D. Lawrence Fellow of The British Diabetic Association, Nuffield Dept. of Clinical Biochemistry, University of Oxford (1982-1984)

Postdoctoral Research Associate, Nuffield Dept. of Clinical Biochemistry, University of Oxford (1984-1985)

Research Fellow, Medical Oncology, University of Southampton (1985-1989)

Senior Research Fellow, Medical Oncology, University of Southampton (1989-1997)

Southampton Senior Research Fellow, University of Southampton (1998-2002)

Reader in Respiratory, Cell and Molecular Biology, University of Southampton (2002 – 2004)

Professor of Respiratory Cell and Molecular Biology, Division of Infection, Inflammation & Immunity, University of Southampton (2004-present)

Director, Allergy and Inflammation Research, University of Southampton 2008-2011

Head of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton 2011-2018

Research interests

Professor Davies’ research is focused on chronic lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) which are a major burden on the healthcare system and represent unmet needs. Her main interests are on the structural cells in the lungs, particularly epithelial cells that form the barrier to the external environment and fibroblasts that are in close communication with the epithelium and together control tissue homeostasis. In chronic lung diseases, disruption of these homeostatic mechanisms affects the local tissue microenvironment and promotes inflammation and tissue remodelling. Her ultimate goal is to use information about disease mechanisms towards development of novel treatments.

Find out more about asthma from Asthma UK
Find out about COPD
Find out about IPF

The Epithelial Barrier in Asthma

The airways are the tubes that conduct air to the gas exchange regions of the lung (alveoli). Their surface is covered by a sheet of specialized cells that form the bronchial epithelium. These cells form a physical barrier to the external environment and secrete mucus that traps inhaled particulates and moves them out of the airways through the action of the mucociliary escalator. We have shown that the epithelial barrier is structurally and functionally defective in asthma, raising the possibility that this defect may facilitate penetration of allergens and trigger allergic inflammation in the lungs of asthmatic subjects. This work suggests that targeting the barrier defect in asthma may offer a novel therapeutic approach for difficult-to-treat asthmatic patients who fail to respond to conventional therapy. A patent for a novel growth factor analogue that restores the barrier properties has been filed.

The Epithelial Barrier and the Common Cold Virus

Respiratory virus infections, especially common cold viruses (known as rhinoviruses, RV) are the major cause of acute asthma (and COPD) exacerbations. Current therapies have little or no effect on the prevention or amelioration of virus-related exacerbations in either children or adults, thereby identifying an unmet medical need. We have pioneered the development and use of in vitro models of asthma and COPD using cells obtained from volunteers at bronchoscopy, allowing mechanistic studies that could not be performed ethically in vivo. Using these models, we have shown that bronchial epithelial cells from volunteers with asthma have a deficient anti-viral response to RV infection, but this can be corrected by provision of the anti-viral protein, interferon beta. This novel finding is protected by a patent and is being exploited by the University’s spin-out company, Synairgen. Inhaled interferon-β is currently being tested in Phase II clinical trials for its ability to reduce or prevent virus-induced asthma exacerbations.

COVID-19

We have used our experience in virus-induced exacerbations of asthma and COPD and expertise in the antiviral activity of IFNb to respond to the COVID-19 pandemic.  In particular, we have addressed reports that IFNb may have a harmful effect in this disease by upregulating ACE2, the receptor used for entry of SARS- CoV-2 into lung cells.  In collaboration with Prof Jane Lucas and Drs Gabrielle Wheway and Vito Mennella who identified a novel variant of ACE2 (short ACE2) which lacks the SARS CoV-2 spike binding region, we have shown that it is this isoform, rather than the virus-binding isoform of ACE2 that is IFN regulated, suggesting that IFN treatment will not promote viral entry. We have also worked closely with colleagues in Synairgen and the NIHR BRC (led by Professor Tom Wilkinson) to support clinical studies of inhaled IFNb for treatment of COVID-19 in hospitalised patients.  On 20 July 2020, Synairgen announced positive results from its Phase II double-blind placebo-controlled trial, called SG016, in hospitalised COVID-19 patients.

The Epithelial-Mesenchymal Trophic Unit

The concept of the epithelial mesenchymal trophic unit (EMTU) was introduced by Evans et al (PMID) and referred to the involvement of the airways structural cells in controlling the local tissue microenvironment during key processes such lung development, repair of damaged tissue, and regulation of inflammatory responses. Our work on dysregulated epithelial repair in asthma has led to the concept that the EMTU is activated in asthma and contributes to disease pathogenesis through aberrant repair responses resulting in tissue remodeling and altered airway function. This paradigm is now widely adopted and cited.

A Disintegrin and Metalloprotease 33 (ADAM33)

ADAM33 was discovered as a novel asthma susceptibility gene by researchers in Southampton in collaboration with US colleagues. Work from our group suggests that ADAM33 may contribute to asthma pathogenesis via a gain-of-function mechanism involving release of the membrane anchored metalloprotease enzyme as a soluble protein (sADAM33) by ectodomain shedding triggered by TGF beta. Our group has identified angiogenesis as the first known biological function for sADAM33. Angiogenesis is known to be increased in asthmatic airways and is associated with reduced lung function, a phenotype that is known to be genetically associated with ADAM3 polymorphism. We have also demonstrated interactions between ADAM33 and maternal allergy that may be relevant to the early life origins of asthma. This work is being taken forward by Dr Hans Michael Haitchi in collaboration with Prof Jeff Whitsett (University of Cincinnati) with demonstration that ADAM33 causes airway remodelling in asthma independently of inflammation.

Tissue engineering – creating an artificial ‘airway’

Use of animal models of allergic airway inflammation for identification of novel targets for therapeutic intervention in asthma have met with only limited success. In humans, asthma tends to run in families, so animal models fail to mimic the interplay between genetic and environmental factors (eg. allergens, viruses, air pollutants) that cause asthma. Recognizing the need for more complex human tissue-based models of disease for studies of disease mechanisms, therapeutic interventions and toxicology, We are developing tissue engineered constructs of the airways. This is being achieved through a variety of interdisciplinary collaborations with colleagues in Electronics and Computer Sciences (Prof Hywel Morgan), Engineering (Prof Martyn Hill) and Chemistry (Dr Martin Grossel). Our work in this area has led to significant funding by NC3Rs and Innovate UK.

Lung fibrosis

This research focuses on the tiny air sacs in your lungs that take up the oxygen you breathe in.  In interstitial lung diseases such as idiopathic pulmonary fibrosis (IPF), the lung tissue becomes damaged and scarred. This thickened, stiff tissue makes it progressively harder to breathe.  IPF has no cure, and existing treatments only slow progression of the disease.  Building on the concept of the epithelial mesenchymal trophic unit, our work has focussed on injury to and/or dysfunction of alveolar epithelium in lung fibrosis disease initiation. 

As in asthma, use of animal models to identify novel targets for therapeutic intervention in IPF have met with only limited success. Therefore, we have developed complex 3D models of fibrosis and have used these to study what factors determine fibrosis progression (rather than tissue repair and resolution). Through interdisciplinary studies, we have identified abnormalities in collagen crosslinking in IPF and have identified LOXL2 as a potential therapeutic target. We are working closely with pharma companies to exploit these models for mechanistic and therapeutic targeting studies.

 

Department(s)

Clinical and Experimental Sciences

Affiliate Department(s)

Respiratory and allergy Research group, Life Sciences

Current PhD students

Christopher Brereton (with Dr Mark Jones) (NIHR BRC funded with AAIR Charity Support)
Joseph Bell (with Drs Jane Collins and Rob Ewing) (Rosetrees/BLF funded with AAIR Charity support)
Chiara Banas (with Dr Emily Swindle) (MRC funded)
Nicola Hepburn (with Drs Mark Jones and Yihua Wang) (AAIR Charity Holgate studentship)

Postgraduate student supervision

1991 Audrey Richter (PhD)
1995 Rosalyn Adam (PhD)
1998 Sarah Puddicombe (PhD)
1999 Nicola Solic (PhD)
2001 Luis Teran (PhD)
2002 Rebecca Mullings (PhD)
2002 Caroline Bell (PhD)
2003 James Lordan (PhD)
2003 Nveed Chaudhary (PhD)
2004 Lynnsey Hamilton (PhD)
2005 James Wicks (PhD)
2005 Christine Boxall (PhD)
2006 Mark Steel (PhD)
2007 Timothy Howell (DM)
2007 Yun Yun Pang (PhD)
2007 Sam Parnia (PhD)
2008 Anna Harvey (MPhil)
2008 Hans Michael Haitchi (PhD)
2008 Jaymin Morjaria (MD)
2010 Nicole Bedke (PhD)
2010 Soo Wei Foo (DM)
2011 David Sammut (PhD)
2011 Chris Grainge (PhD)
2011 Victor Bondanese (PhD, with Tilman Sanchez Elsner)
2011 Gemma Campbell Harding (PhD)
2011 Michelle Hardyman (with Jane Collins)
2012 Wiparat Manuyakorn (PhD)
2013 Matt Loxham
2013 Orestis Andriotis (with Philipp Thurner)
2014 Angela Tait (PhD)
2016 Jessica Donaldson (PhD)
2016 Leanne Wickens (PhD, with Paul Skipp)
2016 Mark Jones (PhD)
2016 Emily Wilkinson (with Jane Collins)
2017 Alison Hill (with Dr Emily Swindle)
2018 Richard Latouche (PhD, with Damon Teagle and Martin Palmer)
2018 Charlene Akoto (with Dr Emily Swindle)
2018 Joanne Kelly (with Dr Hans Michael Haitchi)
2019 Marieke Wandel (with Dr Hans Michael Haitchi)
2019 Hayden Foster (M Phil) (with Dr Emily Swindle)

Faculty of Medicine

Member of Clinical and Experimental Sciences
Director Allergy and Inflammation Research (2008-11)
Head of Clinical and Experimental Sciences Academic Unit (2011-2014)
‘Immunity and Infection’ Pathway Director (until 2018) on the 4 Year Integrated PhD Programme
Member of the Integrated PhD Working Group
Member of NIHR Respiratory Biomedical Research Centre

University of Southampton

Member of the University of Southampton Health and Safety Audit and Assurance Committee
Supervision of undergraduate biomedical sciences student projects
Co-founder of the University spin-out company ‘Synairgen’  

National and International responsibilities

Member of the Medical Research Council (MRC) College of Experts (2004 -8)
Member of the MRC Physiological Systems and Clinical Sciences Board Strategic Review Panel (2004-8);
Member of Asthma UK Scientific Committee (2006-2009)
Member of the Asthma UK fellowship interview panel (2007)
Member of the MRC Subcommittee for the review of the MRC-Asthma UK Centre in Allergic Mechanisms of Asthma, Kings College London (Sept 2010).
Member of the European Respiratory Society’s Standing Evaluation Committee for the Review of Fellowship & Professorship applications (from October 2011-2020)
Member of Asthma UK’s ‘Consensus workshop to establish priority areas for Asthma UK’s research funding 2011-2016.
Member of BBSRC's Training Awards Committee (Committee E) (from 2012-2015)
Member of NC3Rs studentship assessment panel (2014-17)
Member of Academy of Medical Sciences Springboard Panel (2017-2020)
Chair of Trustees Asthma Allergy and Inflammation Research Charity (current)

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Articles

Book Chapter

Conferences

Letters/Editorials

Reviews

Integrated PhD Immunity and Infection pathway – pathway director (until 2018) and PhD supervisor.

BMedSci – Offers up to 2 laboratory placements for study of mechanisms of asthma, COPD and interstitial lung disease. Critical review and E-assignment marker.

BSc Biomedical Sciences - Offers up to 2 laboratory placements for study of mechanisms of asthma, COPD and interstitial lung disease.

MSc in Allergy – delivery of lecture on respiratory viruses

Professor Donna E Davies
Faculty of Medicine, Room AB215, Mailpoint 801, South Academic Block, University Hospital Southampton, Tremona Road, Southampton, SO16 6YD

Room Number: SGH/LF5B/MP810

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