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Medicine

Professor Donna Davies BSc, PhD

Professor of Respiratory Cell and Molecular Biology,, Director of Immunity and Infection Pathway Integrated PhD

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

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 a Lawrence Fellowship from the British Diabetic Association. 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 and then a Readership.

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 and virus-induced exacerbations of asthma and COPD. She has pioneered the use of in vitro models allowing the use of methodologies that could not be used ethically in vivo. Notable discoveries from her work include demonstration of defective epithelial barrier function in asthma 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. This has led to a patent for the use of inhaled interferon-beta (IFN-β) for treatment of virus-induced exacerbations of asthma and COPD. This novel therapeutic is currently in Phase II clinical trials having been developed by ‘Synairgen’, a University of Southampton spin-out company that she co-founded with Stephen Holgate and Ratko Djukanovic in 2003. 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. Current research projects in her laboratory are supported by the MRC, NC3Rs, EPSRC, TSB, Asthma UK and the Roger Brooke Charitable Trust.

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

Responsibilities

Publications

Teaching

Contact

Research interests

Professor Davies’ research is focused on chronic lung diseases such as asthma, COPD and idiopathic pulmonary fibrosis 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.

Why study respiratory 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. 

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

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. Professor Davies’ group has shown recently 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. Prof Davies has 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, her group has 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 (http://www.synairgen.com/). Inhaled interferon-β is currently being tested in Phase II clinical trials for its ability to reduce or prevent virus-induced asthma exacerbations.

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. Prof Davies’ 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 Prof Davies’ 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. Prof Davies’ group has also 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. Her group has 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 through award of an MRC Clinician Scientist and a collaboration with Prof Jeff Whitsett (University of Cincinnati).

IL-4 and IL-13

Th2 cytokines are important triggers of allergic inflammation. Prof Davies and her group have shown that the ‘decoy’ receptor IL-13R2 is an important inhibitor of IL-4, as well as IL-13 signaling, in bronchial epithelial cells and fibroblasts, suggesting that IL-13R2 has broader regulatory activity in the airways than previously recognized. Currently, Dr Allison-Lynn Andrews is investigating how IL-13R2 controls the activity of both Th2 cytokines, through award of an Asthma UK Fellowship.

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, Prof Davies is 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). Her work in this area has led to significant funding by NC3Rs.

Cross disciplinary work

Prof Davies is involved in several cross-disciplinary research activities that have the potential to bring new technologies into the healthcare environment. In addition to the tissue engineering described above, these include developing a label free blood cell analysis system using impedance spectroscopy for point-of-care blood testing (led by Prof Hywel Morgan, funded by TSB and involving a collaboration with Philips) and fabrication and integration of silicon nanowires for evaluation of markers of viral infection using electrical impedance (led by Prof Peter Ashburn and funded by EPSRC/TSB). The latter project takes advantage of her group’s discovery that serum IP-10 levels are highly predictive as a biomarker of viral infection in asthmatics admitted to the emergency room with an exacerbation of their disease. This system, which is aimed at point of care testing, may allow stratification of asthma exacerbations and selection of those patients for whom IFN-β therapy is indicated.

Histological section of an airway from someone who died of an acute asthma attack. The airway is almost completely obstructed due to contraction of the bronchial smooth muscle and the lumen is further
Figure 1
Schematic representation of the EMTU.  In asthma, epithelial susceptibility to damage initiates signals that are amplified by underlying fibroblasts and propagated into the deeper layers of the submuc
Figure 2
Scanning electron micrograph of cilia on the surface of a tissue engineered construct
Figure 3

Department(s)

Clinical and Experimental Sciences

Affiliate Department(s)

Respiratory and allergy Research group

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)

Current

Gemma Campbell Harding
Matt Loxham
Wiparat Manuyakorn
Angela Tait
Jessica Donaldson (starting Oct 2011)

Michelle Hardyman (with Jane Collins)
Victor Bondanese (with Tilman Sanchez Elsner)
Emily Wilkinson (with Jane Collins)
Marcel Fowler (with Hywel Morgan)
Orestis Andriotis (with Philipp Thurner)

Faculty of Medicine

Member of Clinical and Experimental Sciences
Director Allergy and Inflammation Research
Member of Research Strategy Committee
‘Immunity and Infection’ Pathway Director on the 4 Year Integrated PhD Programme
Member of the Integrated PhD Working Group
Member of the Integrated PhD In Biomedical Sciences CDA Sub-Committee
Member of Website working group
Member of NIHR Respiratory Biomedical Research Unit

University of Southampton

Member of the University of Southampton Strategic Research Group for Nanotechnology.
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 MRC/ABPI COPD Initiative.
Member of the European Respiratory Society’s Standing Evaluation Committee for the Review of Fellowship & Professorship applications (from October 2011).
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 (from Jan 2012)

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Articles

Book Chapter

Conferences

Review

Integrated PhD Immunity and Infection pathway – pathway director and 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 Davies
Faculty of Medicine, University of Southampton, Building 85, Life Sciences Building, Highfield Campus, Southampton, SO171BJ

Room Number: SGH/LF5B/MP810

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