ADAM33 gene and environment interactions in developing lungs and their involvement in the early life origin of asthma

Lead Research Organisation: University of Southampton
Department Name: Clinical and Experimental Sciences

Abstract

Asthma is a common disease affecting both adults and children. It causes wheeziness, chest
tightness and cough and is often triggered by exposure to allergens (eg. dust or animal fur). As a
result, the airways contract too much and too easily, limiting airflow into the lung. Asthma tends to
run in families suggesting there are ‘asthma’ genes. ADAM33 is such a gene where small changes
have been found in people with asthma and in young children at risk of asthma. It is found in
specialized airway ‘smooth muscle’ cells (ASMCs) that cause airway ‘twitchiness’ in asthma and it is
released in fluid that is present in the airways of asthmatic patients. In baby lungs, I have found
that ADAM33 occurs in stem cells that give rise to ASMCs. Therefore, the objectives of my research
are to study the role of ADAM33 in airway development and to understand whether release of
ADAM33 can give rise to abnormal ASMC development that might lead to asthma. I will also
investigate whether, and how maternal allergy, a factor that predisposes babies for asthma, affects
ADAM33 in ASMC. These studies should help devise new treatments for asthma close to the origin of
the disease.

Technical Summary

Aims: A Disintegrin And Metalloprotease (ADAM)33 is a susceptibility gene associated with asthma,
bronchial hyperresponsiveness (BHR) and reduced lung function in young children. High levels of a
55 kDa soluble fragment of ADAM33 (sADAM33) have been found in bronchoalveolar lavage fluid
(BALF) of asthmatic subjects where levels correlate with reduced lung function. To investigate the
early life contribution of ADAM33 to asthma pathogenesis, I have found that ADAM33 expression
increases when spontaneous peristaltic contractions of the airways commence in utero and when the
lungs inflate post partum. Using human embryonic lung explants, I have found that recombinant
sADAM33 enhances smooth muscle development, identifying a novel function for sADAM33.
Furthermore, in genetically susceptible A/J mice, I have found that maternal allergy suppresses
ADAM33 expression in the offspring and that this is associated with reduced airways smooth muscle
and increased airway reactivity. This suggests a gene-environment interaction that leads to altered
airway structure and function. Based on these observations I now wish to test the hypothesis that
ADAM33 influences bronchial smooth muscle growth to affect airway development and that
environmental factors in utero interact with ADAM33 leading to a vulnerable airway structure that
predisposes to the development of asthma in childhood or later in life.
Objectives & Methods:
To test my hypothesis I will address these questions:
1. What is the effect of maternal allergy on airway development and its consequences on airway
structure and function in juvenile mice? This will involve in depth imaging of the airway structure
and correlation with airway mechanics and function. To assess the potential for gene-environment
interactions, the studies will use both A/J (BHR1/ADAM33 positive) and BALB/c (BHR1 negative)
mice.
2. Does release of sADAM33 affect smooth muscle growth, airway development and post natal
airway function? This will be assessed using a conditional transgenic mouse expressing sADAM33;
the consequences of altered structure on airway function will be assessed.
3. Do the ADAM33 mechanisms identified in murine lung development occur in developing human
lungs? This will be assessed using gain or loss of function approaches applied to human embryonic
lung explants. I will determine whether sADAM33 is detectable in vivo in amniotic fluid from allergic
mothers and BALF from paediatric asthma patients.
Scientific opportunities: These studies will provide new insight into gene-environment
interactions in utero and their effect on the early origins of asthma. This might lead to novel
prevention and intervention strategies early in life.

Publications

10 25 50
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Maeda Y (2011) Airway epithelial transcription factor NK2 homeobox 1 inhibits mucous cell metaplasia and Th2 inflammation. in American journal of respiratory and critical care medicine

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Whitsett JA (2011) Intersections between pulmonary development and disease. in American journal of respiratory and critical care medicine

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Yang Y (2012) Regulation of a disintegrin and metalloprotease-33 expression by transforming growth factor-ß. in American journal of respiratory cell and molecular biology

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Davies ER (2012) Spiruchostatin A inhibits proliferation and differentiation of fibroblasts from patients with pulmonary fibrosis. in American journal of respiratory cell and molecular biology

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Korfhagen TR (2012) SAM-pointed domain ETS factor mediates epithelial cell-intrinsic innate immune signaling during airway mucous metaplasia. in Proceedings of the National Academy of Sciences of the United States of America

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Sanders PN (2013) CaMKII is essential for the proasthmatic effects of oxidation. in Science translational medicine

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Davies Elizabeth R. (2014) Airway remodelling induced by ADAM33 is reversible in EUROPEAN RESPIRATORY JOURNAL

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Haitchi HM (2014) Asthma und Adipositas - gefährliche Zwillinge. in Aerzte Krone, Themenheft Pneumologie

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Chen G (2014) Foxa3 induces goblet cell metaplasia and inhibits innate antiviral immunity. in American journal of respiratory and critical care medicine

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Lange AW (2014) Sox17 is required for normal pulmonary vascular morphogenesis. in Developmental biology

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Haitchi HM (2014) Asthma and obesity - dangerous twins in JATROS Pulmologie and HNO

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Hoffmann J (2015) Compartment-specific expression of collagens and their processing enzymes in intrapulmonary arteries of IPAH patients. in American journal of physiology. Lung cellular and molecular physiology

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Davies E (2019) Regulation of ectodomain shedding of ADAM33 in vitro and in vivo in Journal of Allergy and Clinical Immunology

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Azim A (2020) New Perspectives on Difficult Asthma; Sex and Age of Asthma-Onset Based Phenotypes. in The journal of allergy and clinical immunology. In practice

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Davies ER (2020) Involvement of the epidermal growth factor receptor in IL-13-mediated corticosteroid-resistant airway inflammation. in Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

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Fong WCG (2021) Asthma did not increase in-hospital COVID-19-related mortality in a tertiary UK hospital. in Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

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Azim A (2021) Clinical evaluation of type 2 disease status in a real-world population of difficult to manage asthma using historic electronic healthcare records of blood eosinophil counts. in Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

 
Title Wooden moveable fish 
Description While I was in Cincinnati, USA from 2010-2011 for my research project as part of the MRC Clinician Scientist Fellowship a saw a bill board with a gold-fish out of water with the quote: " When I have an asthma attack I fell lie a fish with no water" JESSE, age 5. This was part of a film of a fish out of water as awareness advertisement for asthma attacks from the webpage https://www.noattacks.org. This has inspired me as a trained joiner who loves to work with wood to make movable wooden fish based on this bill board and movie. I have also started to sell these fish and a proportion of these sales goes to charities that support my asthma research (AAIR, Asthma UK). 
Type Of Art Artwork 
Year Produced 2017 
Impact Selling this fish on the high-street in Winchester on weekends before Christmas has enabled me to talk to many people and explain why I make these fish and how they are related to my research work. I have also handed out a leaflet explaining this and referring to the fish out of water from the bill board advert in the USA. Since 2018 I have now also a personal webpage about my woodworking hobby and a bit about my asthma research. I have sold or given away fish in many countries in Europe (Austria, Germany, Switzerland, France, UK) and the rest of the world (USA, Canada). One of my large bendable fish has been donated to the Medical Research Foundation, where it is exhibited as "Researchfish" in their office. 
URL http://www.carrotbird.com
 
Description Member of Senate, University of Southampton
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Membership of a guideline committee
Impact As member of Senate at the University of Southampton we had to vote on changes in the regulator environment for undergraduate and postgraduate students as well on new implementations to improve educational and skill levels of the University workforce. Our decisions have also impacted local communities and social services in particular related to students and change in policies.
 
Description Member of Wessex Asthma Network (WAN) steering and business committee
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Membership of a guideline committee
Impact The Wessex Asthma Network (WAN) continued to evolve and engage a widening audience. That evolving regional role has seen an 80% rise in our tertiary patient population in the past 5 years which now accounts for 51% of our workload. The Difficult Airways Disease Service at University Hospital Southampton (UHS) saw continued growth and development in 2018 alongside new challenges and service requirements in line with the status of being a formally Commissioned Regional Centre for Severe Asthma. Our Regional role continued to expand and by the end of the year we were caring for 524 tertiary patients within a clinic population of 1034 patients which in turn had grown 12% in 12 months. In parallel, it has also seen a 321% rise in our use of biological therapies which has created significant capacity pressures on our service while realising significant patient benefit. Added pressures included a reduction in Consultant input and high demand on limited nursing resource. Simultaneously, research activity through our service continued to grow. In 2018 the WATCH study successfully undertook studies funded by the NIH and from Industry partners and had enrolled nearly 500 patients.
 
Description AAIR Charity Research Grant 2013
Amount £23,100 (GBP)
Organisation Asthma Allergy & Inflammation Research 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2013 
End 03/2015
 
Description AAIR Charity Research Grant 2014
Amount £11,800 (GBP)
Organisation Asthma Allergy & Inflammation Research 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2014 
End 01/2015
 
Description AAIR Charity Stephen T Holgate PhD Studentship 2014
Amount £106,000 (GBP)
Organisation Asthma Allergy & Inflammation Research 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2014 
End 10/2018
 
Description AAIR Travel Fellowship 2015
Amount £1,400 (GBP)
Organisation Asthma Allergy & Inflammation Research 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2015 
End 11/2015
 
Description Asthma Allergy and Inflammation Research (AAIR) charity equipment grant, Southampton, UK
Amount £4,812 (GBP)
Organisation Asthma Allergy & Inflammation Research 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2019 
End 09/2020
 
Description Asthma, Allergy & Inflammation Research (AAIR) Charity, UK Grant: Study of proteins, lipids and oxidative stress markers in lungs from Adam33 knock out mice that were challenged with allergen using proteomics, lipidomics and oxidomics
Amount £5,780 (GBP)
Organisation Asthma Allergy & Inflammation Research 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2018 
End 07/2019
 
Description Asthma, Allergy & Inflammation Research (AAIR) Charity, UK Grant: The role of EGFR inhibition in Corticosteroid-Resistant Neutrophilic Airway Inflammation Caused by IL-13
Amount £10,975 (GBP)
Organisation Asthma Allergy & Inflammation Research 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2018 
End 04/2019
 
Description Asthma, Allergy & Inflammation Research (AAIR) Charity, UK equipment Grant: Tissue slicer for precision cut lung slices (PCLS).
Amount £7,558 (GBP)
Organisation Asthma Allergy & Inflammation Research 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2018 
End 01/2019
 
Description British Medical Association (BMA) Foundation for Medical Research: Jon Moulton Asthma Research Grant: The impact of the asthma gene, ADAM33, on innate immunity and susceptibility to allergic airways inflammation
Amount £64,300 (GBP)
Organisation British Medical Association (BMA) 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2018 
End 11/2021
 
Description EPSRC Bridging the Gap grant 2012
Amount £9,658 (GBP)
Organisation University of Southampton 
Sector Academic/University
Country United Kingdom
Start 10/2012 
End 04/2013
 
Description ERS short term research training fellowship for PhD student from Salzburg Austria, 2010
Amount £4,500 (GBP)
Organisation European Respiratory Society (ERS) 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2011 
End 09/2011
 
Description Faculty of Medicine, University of Southampton Research Management Committee Fund 2011
Amount £15,000 (GBP)
Organisation University of Southampton 
Sector Academic/University
Country United Kingdom
Start 02/2011 
End 08/2013
 
Description Lung Science Grant
Amount € 19,891 (EUR)
Organisation Austrian Society of Pneumology 
Sector Learned Society
Country Austria
Start 09/2016 
End 09/2020
 
Description Medical Research Foundation (MRF) and Asthma UK Research Grant 2015
Amount £292,000 (GBP)
Funding ID MRFAUK-2015-322 
Organisation Medical Research Council (MRC) 
Department Medical Research Foundation
Sector Charity/Non Profit
Country United Kingdom
Start 01/2016 
End 12/2019
 
Description Multiomic approach to study the impact of maternal allergic asthma during pregnancy on asthma related mediators including ADAM33 in biologic samples collected during caesarean sections.
Amount £64,954 (GBP)
Organisation British Medical Association (BMA) 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2019 
End 11/2022
 
Description NC3R grant for non-mammalian models for asthma research
Amount £89,000 (GBP)
Funding ID NC/M001482/1 
Organisation National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2015 
End 05/2017
 
Description OEGP-Short term fellowship 2012 for PhD student from Salzburg, Austria
Amount € 5,000 (EUR)
Organisation Austrian Society of Pneumology 
Sector Learned Society
Country Austria
Start 10/2012 
End 10/2013
 
Description Optimizing ADAM33-targeted ASOs for clinical development for asthma and COPD.
Amount $188,000 (USD)
Organisation University of Massachusetts 
Sector Academic/University
Country United States
Start 12/2019 
End 12/2021
 
Description Prevention and treatment of allergic asthma in vivo using ADAM33 silencing oligonucleotides.
Amount £24,678 (GBP)
Organisation Medical Research Council (MRC) 
Department MRC Confidence in Concept Scheme
Sector Charity/Non Profit
Country United Kingdom
Start 11/2019 
End 03/2021
 
Description University of Southampton Annual Adventure in Research Grant 2011
Amount £19,968 (GBP)
Organisation University of Southampton 
Sector Academic/University
Country United Kingdom
Start 03/2011 
End 02/2013
 
Description University of Southampton Postgraduate Research Scholarship Fund 2010
Amount £21,000 (GBP)
Organisation University of Southampton 
Sector Academic/University
Country United Kingdom
Start 10/2010 
End 10/2013
 
Description Wessex Medical Research Innovation Grant 2011
Amount £20,000 (GBP)
Organisation University of Southampton 
Sector Academic/University
Country United Kingdom
Start 09/2011 
End 10/2013
 
Title ADAM33-Ecto transgenic mouse 
Description Lung specific conditional transgenic ADAM33-Ecto mouse 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Provided To Others? No  
Impact This mouse will enable us to study the function of human ADAM33 in an in vivo lung model. 
 
Title ADAM33-MP transgenic mouse 
Description Lung specific conditional transgenic ADAM33-MP mouse 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Provided To Others? No  
Impact This mouse will enable us to study the function of human ADAM33 in an in vivo lung model. 
 
Title Adam33-knock out mouse 
Description Adam33 knock out mouse 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Provided To Others? No  
Impact We did not have to generate this mouse from scratch because this mouse was regenerated from sperm which we received from the University of California San Francisco. 
 
Title Adaptation of Iodine stain of tissue for Micro CT imaging 
Description During my time I have adapted and used iodine in form of Lugol solution to stain different mouse and human tissues to enhance the radiographic contrast for Micro CT imaging 
Type Of Material Technology assay or reagent 
Year Produced 2012 
Provided To Others? Yes  
Impact Using this adapted method has resulted in images that show the hydroureter and hydronephrosis development in a Klf-5 mutant mouse model (PMID: 21803035). We also further used this method to study the role of Sox17 in pulmonary angiogenesis in a mouse model using Micro CT image analysis of whole ED18 embryonic Micro CTs In Cincinnati Children's Hospital Medical Center, Ohio, USA. Analysis of the CT scans was done in collaboration with Philipp Thurner and Nick Udell from the Bioengineering Group at the School of Engineering Science at the University of Southampton (AW Lange, HM Haitchi, A Sridharan, N Udell, P Thurner, SE. Wert, Yan Xu, JA. Whitsett. Sox17 is required for normal pulmonary vascular morphogenesis, Dev Biol. 2014 Mar 1;387(1):109-20). 
URL http://europepmc.org/abstract/MED/21803035
 
Title Precision cut lung slices (PCLS) to study airway reactivity to different stimuli ex vivo and in vitro 
Description In 2019 my group acquired a microtome for precision cult lung slicing (PCLS). This allows us to study lung sections from our different ADAM33 mouse models ex vivo and in vitro We are in particular interested in studying airway reactivity in response to allergens and different inhibitory compounds in PCLSs. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2018 
Provided To Others? Yes  
Impact PCLS is a very helpful tool to reduce the number of animals need to test airway reactivity in vivo. It was used by my PhD student and resulted in important data of our ADAM33 research that formed part of a chapter in her PhD thesis (completed Dec 2019). 
 
Title Maternal Environment in Pregnancy (MEP) study 
Description In this study we will investigate the influence of the Maternal Environment in Pregnancy (MEP) on the unborn child and the development of lung disease such as asthma in early life. We will collect maternal blood and urine, amniotic fluid, fatal umbilical blood, placenta and umbilical cord during caesarean section. This study is a collaboration with my obstetrician colleague Mr Matthew Coleman from Princess Ann Hospital, University Hospital Southampton NHS-FT. The study will allow us collect clinical data from the mother and newborn and to establish a database (using an ALEA tool) and biobank of all the samples collected. The study has full ethical and HRA approval 19/LO/0175 and has be adapted to the NIHR Wessex Clinical Research Network portfolio. As part of a pilot study within the MRF/AUK grant we want to translate our early life findings from our ADAM33 mouse models (mice generated as part MRC Clinician Scientist Fellowship G0802804) into human disease and will study soluble ADAM33 in the amniotic fluid from 10-15 mothers with and without asthma. We were also successful in getting an grant award from the BMA Foundation for Medical Research The James Trust grant for research into asthma in 2019 using multiomic approaches to study the biological samples from the MEP study. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? No  
Impact This database of clinical data and biological samples will become an invaluable tool for our future asthma research in early life. We had already interest from three other national CRNs, who asked if they could become a site on the study. Based on our initial pilot study we will consider including other national research centres. We had also already interest by our collaborators in Cincinnati Children's Hospital Medical Center in the USA. As part of our collaboration they would do the proteomics analysis on maternal and fatal plasma and amniotic fluid and RNA-Seq on the placentas from mothers with and without asthma. In particular we would be interested in ADAM33 and other asthma related mediators, that might be developed as clinical biomarker for asthma in early life. We have been awarded the grant from the BMA Foundation for Medical Research in November 2019. 
 
Title The Wessex AsTHma CoHort of difficult asthma (WATCH) 
Description The Wessex AsTHma CoHort of difficult asthma (WATCH) is a longitudinal cohort study to facilitate better understanding and management of difficult asthma encountered in clinical practice. This is a real life study patients recruited from our Difficult to Treat Asthma Clinic. Until today we have recruited almost 500 patients with difficult asthma. We have full ethical approval and patient consent to share these anonymised data with sub-projects that have resulted from this cohort and are funded by industry, NIHR and NIH. 
Type Of Material Database/Collection of data 
Year Produced 2014 
Provided To Others? No  
Impact Based on the WATCH cohort we have established collaboration with industry and national and international institutions. We have also now submitted 11 abstract for presentation at the European Respiratory Society meeting in Paris in September 2018 and one manuscript has been recently published in 2019 and two further manuscripts are in preparation. WATCH has already generated considerable interest from other research groups and will definetly result in further collaborations. 
URL https://bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-019-0862-2
 
Description ADAM33 in COPD and Lung Tumours 
Organisation Paracelsus Private Medical University of Salzburg
Country Austria 
Sector Academic/University 
PI Contribution We help to set up a clinical study in Salzburg writing a research protocol and providing clinical study protocols and forms. We were closely involved in the ethical approval application in Salzburg. We also provided research reagents and plastics which were sent to Salzburg for sample collection. Biological samples were received and processed further in Southampton. A PhD student from Salzburg has spent several 1 to 3 months periods in Southampton analyse the samples from Austria.
Collaborator Contribution Our partner was fully in involved in writing a research protocol and submitting this to their local ethical commission. Furthermore, they provided and sent research samples to Southampton for further analysis. A part-time PhD student at the PMU spend several month in Southampton as part of the research project and for her PhD in 2010, 2013, 2016. The PhD student has submitted her thesis in February 2017 and successfully passed her viva in May 2017.
Impact Results from this work have been presented as oral presentation at the European Respiratory Society (ERS) Congress in Viennna, Austria in 2012. A manuscript is in preparation for publication in 2020.
Start Year 2006
 
Description ADAM33 in lung vascular research and the role of p22phox in asthma 
Organisation Ludwig Boltzmann Society
Department Ludwig Boltzmann Institute for Lung Vascular Research
Country Austria 
Sector Academic/University 
PI Contribution Purification of recombinant ADAM33 protein and provision of protein for in vitro studies as well as ADAM33 knock out mouse in future for in vivo studies. Use of expertise about ADAM33 for experiments and interpretation of data from human samples of lung fibrosis. RTqPCR experiments to study expression of p22phox in bronchial samples from patients with asthma and healthy control subjects and analysis of the data.
Collaborator Contribution Use of recombinant ADAM33 in established lung vascular research models. Combining our human data with mouse derived data and experiments in Graz.
Impact Collaboration as part of COST Action (European Cooperation in Science and Technology) BM1201: Developmental Origins of Chronic Lung Disease. A manuscript was published describing the expression of ADAM33 in pulmonary fibrosis in Am J Physiol Lung Cell Mol Physiol. 2015 May 15;308(10):L1002-13. A manuscript describing the role of p22phox in asthma has been published in Antioxidants and Redox Signaling in December 2017. PMID: 28510479
Start Year 2013
 
Description COST Action BM1201 
Organisation European Cooperation in Science and Technology (COST)
Country Belgium 
Sector Public 
PI Contribution As a member of COST Action BM1201 I have been invited to give a talk about my research on the role of ADAM33 in lung development at the first COST Conference in Munich, Germany from the 13-15 June 2013. This was closely related to the COST Action about the Developmental Origins of Chronic Lung Disease.
Collaborator Contribution COST Action provided a travel support for the first COST conference and enable me to meet scientists in the same field as my MRC funded research interest. COST will also provide financial support for short term collaborative visits between different European countries. My postdoctoral research on the MRF/AUK grant submitted and abstract and was invited for an oral presentation at the final Annual Meeting of COST BM 1201: Early Origins of Chronic Lung Disease: "The end of the beginning". Athens, Greece, 3-4th of November 2016.
Impact Following the 1st COST meeting a research collaboration has been established with a research group in Graz, Austria. From this collaboration a first manuscript was published in Am J Physiol Lung Cell Mol Physiol. 2015 May 15;308(10):L1002-13 and a second manuscript has been submitted to Antioxidants & Redox Signaling in 2017. Although the COST Action BM1201 had its final meeting in November 2016 I have also established collaborations with Professors. Seal Salani & Andrew Bush from Imperial College London, who were both members of COST BM1201 and are now collaborators on the MRF/AUK 2015-322 grant.
Start Year 2012
 
Description Discovery of novel ADAM33-MP inhbitors 
Organisation University of Southampton
Department Faculty of Natural and Environmental Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution I sought the collaboration with the department of chemistry with the aim to us the Zinc data base and computational modelling to find novel inhibitors for the metalloprotease of ADAM33 using the existent crystal structure. I then test novel compounds that arose from these searches in our FRET-based peptide cleavage essay for screening to find the most promising inhibitors and then performing IC50 assays.
Collaborator Contribution Our collaborators from the department of chemistry have used the Zinc data base and different docking softwares to find and design novel and specific ADAM33 inhibitors.
Impact This has resulted in the discovery of several very promising compounds. We have signed confidential and material exchange agreement with MRC-Technology and industry that provided with access to compound libraries. This enabled us to test the most promising compounds in our computational modelling softwares, order the most promising compounds and test them in our FRET peptide assays. The next step is to get the crystal structure of ADAM33 with and without the compounds and test the compounds in our transgenic ADAM33 mouse models. This collaboration has resulted in further grant support by the Asthma Allergy & Inflammation Charity in 2013. We have also submitted a preliminary application for a Wellcome Trust Seeding Drug Discovery scheme in Nov 2014 which was not successful. We have started discussion with industry to take this exciting development of ADAM33-MP inhibitors further in 2015/2016.
Start Year 2011
 
Description Inhibition of ADAM33 by advanced oligonucleotides to reverse pathological airway remodeling in asthma 
Organisation University of Massachusetts
Department University of Massachusetts Medical School
Country United States 
Sector Academic/University 
PI Contribution This is a collaboration between Associate Professor Dr. Jonathan Watts and his group, which started a few years ago when he was working at the University of Southampton. In 2015 he moved to the University of Massachusetts Medical School. I have provide the initial idea to develop novel oligonucleotides for inhibition of the asthma gene ADAM33, which was based on preliminary data from siRNA experiments from my PhD work.
Collaborator Contribution Jon has made some novel oligonucleotides, which we have tested in different cell lines and are strong inhibitors of human and mouse ADAM33. We have now started to use these ADAM33 anti-sense oligonucleotides (ASOs) as preventative and therapeutic intervention in our allergic airway inflammation mouse models as potential novel asthma therapy. This has been funding by a MRC Confidence in Concept grant from the University of Southampton in 2019.
Impact We submitted a grant application to the American Asthma Foundation Research Program for the 2016 AAF Scholar Award in December 2016, which got ranked very highly, but AAF was not able to find this work. I was named as co-inestitgator. The aim was use our ADAM33 mouse models from here in Southampton to test some of the novel oligonucleotides that will be generated in the US. We prepared and filled a patent application for these new oligonucleotide compounds in 2017. This is currently under review. Furthermore, a manuscript is has been published in Molecular Therapy - Nucleic Acids in September 2017. PMID: 28918018 We were successful in receiving further funding from a MRC Confidence in Concept grant and University of Massachusetts Bridge Grant further develop ASOs and use them for the first time in asthma mouse models in 2019.
Start Year 2015
 
Description Investigation of the influence of the Maternal Environment in Pregnancy (MEP) on the unborn child and the development of lung disease such as asthma in early life. 
Organisation Princess Anne Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution Based on our animal models of maternal allergic airway inflammation during pregnancy at its effect on their offspring we started a collaboration with Mr Matthew A Coleman, an obstetrician at Princess Ann Hospital to study the effect of the Maternal Environment in Pregnancy (MEP), in particular maternal allergic asthma, on the development of asthma in their babies.
Collaborator Contribution Dr Coleman is a consultant obstetrician and clinical researcher who is the Princess Ann hospital and regional lead for maternal medicine and in particular the care of women with significant medical comorbidities including asthma.
Impact Based on our collaboration we were awarded successfully a BMA The James Trust grant 2019 with the title: Multiomic approach to study the impact of maternal allergic asthma during pregnancy on asthma related mediators including ADAM33 in biologic samples collected during caesarean sections.
Start Year 2018
 
Description Maternal allergen exposure mouse model, Detroit, US 
Organisation Wayne State University
Department Department of Family Medicine and Public Health Sciences
Country United States 
Sector Academic/University 
PI Contribution I personally spent some time in the lab in Detroit and helped to plan and set up the experiments and helped with the use of invasive lung function methods. Furthermore, samples send from Detroit will be further analysed in Southampton, UK.
Collaborator Contribution The collaborator Professor David Bassett in Detroit helped in setting up a maternal allergen exposure mouse model and performed experiments on these mice and their offspring. These included performing non-invasive and invasive lung function measurements and collecting and shipping of samples to the UK. Our laboratory is in the process of receiving lung function and animal exposure equipment on loan from the laboratory in the US which will be additional to our own small animal challenge and lung function laboratory in the UK. In 2014 and 2016 we have received equipment from the lab in Detroit for doing non-invasive lung function measurements (Buxco System for Penh measurements). This has allowed us to expand our small animal lung function laboratory at the University of Southampton in 2017. Professor Basset has come for regular meeting to Southampton in 2016 and 2017 and has given us helpful advice in doing our allergen challenge models as well as performing lung function analysis in our ADAM33 mouse models.
Impact Manuscript is in preparation for submission to Clinical and Experimental Allergy in 2020.
Start Year 2011
 
Description Multiomic approach to study the impact of maternal allergic asthma during pregnancy on asthma related mediators including ADAM33 in biologic samples collected during caesarean sections. 
Organisation Cincinnati Children's Hospital Medical Center
Country United States 
Sector Hospitals 
PI Contribution As part of a BMA The James Trust grant for research into asthma we have collected maternal plasma, amniotic fluid, fetal plasma and placenta during Caesarean deliver from mother with and without asthma. These will be send to Cincinnati for mass spectrometry and RNA Sequencing analysis.
Collaborator Contribution Proffessors Jeffrey A Whitsett & Assem G Ziady will do the mass spec and RNA sequencing analysis for us at Cincinnati Children's Hospital Medical Center, USA
Impact N/A
Start Year 2019
 
Description Novel oligonucleotides and conjugates for ADAM33 asthma research and therapy 
Organisation University of Southampton
Country United Kingdom 
Sector Academic/University 
PI Contribution We provided cell lines and sequences for ADAM33 siRNA, antibodies, RTqPCR reagents and also space to do experiments in our laboratory.
Collaborator Contribution The partner developed and synthesised novel oligonucleotides, which they tested in biological assays in their and our laboratory.
Impact Our work has been presented at national and international conferences in abstract form. We have also prepared a manuscript for submission in 2016.
Start Year 2012
 
Description Olink analysis of biologic samples collected during caesarean sections. 
Organisation Olink Bioscience
Country Sweden 
Sector Private 
PI Contribution We will provide maternal and fetal plasma and amniotic fluid from the Maternal Environment in Pregnancy (MEP) study.
Collaborator Contribution Olink will analyse the biologic samples collected during caesarean sections.
Impact N/A
Start Year 2019
 
Description Purification of recombinant ADAM33 and crystal structure of ADAM33-MP inhibitor complexes 
Organisation University of Southampton
Department Faculty of Natural and Environmental Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Our team provides the conditional medium from ADAM33-MP stably tranfected insect cells for purification of ADAM33-MP at the Institute for Life Sciences at the University of Southampton. We also tested the compounds discovered in collaboration with chemistry to find the most promising ones that will be used to get the ADAM33-MP complex crystal structure. We recently developed a collaboration in order to scale up our protein purification with the protein purification group at Cancer Research at the University of Southampton (Aug 2013).
Collaborator Contribution Our collaborators help with the purification of ADAM33-MP which will provide enough protein for crystal structure analysis.
Impact We have now already purified protein in large scale that we can use for our FRET peptide based assays and protein has also been send to our Italian collaborators who use the protein in angiogenesis based assays. In 2014 we have now also established stably transfected insect cells not only with human ADMA33-MP-Pro (active and mutated inactive) but also for the mouse ADAM33 (active and mutated inactive), which we have been using for purification of recombinant human and mouse ADAM33. In 2015 we have used the recombinant ADAM33 protein in cell culture experiments and will use more of the protein in 2016. We have now a working protocol for the purification and will try to increase our yield for crystallography in 2016.
Start Year 2011
 
Description Purification of recombinant soluble ADAM33 and functional studies 
Organisation University of Pisa
Department Clinical Immunology/Rheumatology Units
Country Italy 
Sector Academic/University 
PI Contribution We provided the stably transfected insect cells and reagents and apparatus necessary for purification of soluble ADAM33. Supervision of PhD student from Pisa, Italy. Provision of purified soluble ADAM33 to the group in Italy.
Collaborator Contribution A PhD student from Pisa came over to work for 6 months in our laboratory and purify soluble ADAM33. Purified soluble ADAM33 has been used for different in vitro and in vivo functional assays. The partner have set up also a HUVEC tube formation assay which they will use to test some of our novel anti-ADAM33 compounds. The partner has also set up chic chorioallantoic membrane (CAM) assays as an angiogenesis assay for soluble ADAM33 and our novel small compound inhibitors.
Impact This collaboration has allowed us to scale up our purification of soluble ADAM33, which we use in our ex vivo culture models and also for screen novel compounds as ADAM33 inhibitors using a FRET assay. We also use this purified recombinant soluble ADAM33 protein in our FRET assays of samples from our ADAM33 mouse models as part of the MRF/AUK grant. Work from this collaboration has resulted in an Abstract presentation at European Academy of Allergy and Clinical Immunology (EAACI) Congress in Barcelona in 2015. A manuscript is presently in preparation for submission in 2018.
Start Year 2012
 
Description Reactive Oxgen Species in Asthma 
Organisation University of Iowa
Department Department of Internal Medicine
Country United States 
Sector Academic/University 
PI Contribution This collaboration has allowed me as a MRC clinician scientist to use our samples from patients for new experiments in order to study novel mechanisms in the pathogenesis of asthma that are related to my research interest.
Collaborator Contribution This collaboration gave us access to a new field in asthma research and we might use some of the tools developed in Iowa for our research.
Impact This collaboration resulted in a joint publication PMID 23884469.
Start Year 2012
 
Description The effect of Non-typeable Haemophilus influenzae (NTHI) on transgenic IL-13 mice 
Organisation University of Oxford
Department Nuffield Department of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Our team provided the conditional transgenic IL-13 mouse that causes an IL-13 induced allergic airway inflammation as a murine model for asthma.
Collaborator Contribution Dr Timothy Hinks is a Wellcome Trust Career Development Fellow in Respiratory Immunology, Nuffield Dept of Medicine at the University of Oxford. He will use a transgenic IL-13 mouse model to study the effect of Non-typeable Haemophilus influenzae (NTHI) on IL-13 induced allergic airway inflammation.
Impact N/A
Start Year 2019
 
Description Transgenic mouse models in respiratory research Cincinnati, US 
Organisation Cincinnati Children's Hospital Medical Center
Department Section of Neonatology, Perinatal and Pulmonary Biology
Country United States 
Sector Academic/University 
PI Contribution access to samples and data, training of staff, significant intellectual & practical input into collaborative research.
Collaborator Contribution access to equipment & facilities, training of staff, significant intellectual input into research.
Impact The access to samples and data from the University of Southampton resulted in joint publications PMID: 21562130 & PMID: 21642246. Furthermore, I was able to apply my expertise in Micro-CT to samples in CCHMC and to further develop a contrast enhancing method for Micro-CTs resulting in another joint publication PMID: 21803035. As part of my MRC-CRF I was able to generate two transgenic ADAM33 mouse lines and regenerate an ADAM33-null mouse which will now be available in Southampton. We have also generated novel micro-array data from cystic fibrosis and healthy primary paediatric epithelial cell cultures which will enable us to write joint grant applications. Part of this work has been submitted as scientific abstract at the American Thoracic Society (ATS) meeting 2012. The access to an IL-13 transgenic mouse model has resulted submission of two more scientific abstracts at the ATS meeting 2012. Further work done in collaboration on SPDEF in Cincinnati resulted in the joint publication PMID 23012424. First results from ADAM33 work has been submitted and presented as scientific abstract to American Thoracic Society (ATS) meeting in San Diego, USA in 2014 and European Respiratory Society (ERS) Congress in Munich, Germany in 2014. In 2014, RNA samples for transgenic mouse lungs have been sent to Cincinnati Children's Hospital Research Centre (CCHMC) for next generation sequencing and bioinformatic analysis. In 2015 my PhD student spent 3 week bioinformatics training using our NGS data from the transgenic ADAM33 mice in CCHMC. We will also send more samples from the ADAM33 knock out mouse for NGS to CCHMC in 2016. As part of the recently awarded MRF-AUK grant (2015) we will do more NGS together with CCHMC and a PhD student will go for further training in bioinformatics and lung biology to CCHMC in 2017/2018. In 2016 we published our data from human samples and our ADAM33 mouse models in JCI Insight PMID: 27489884. This publication has made a significant contribution to our understanding how soluble ADAM33 initiates airway remodelling, which promotes susceptibility for allergic asthma in early life. The publication has attracted wide attention by national and international media and the scientific community. We continued to use all genetically engineered mouse model that we generated in Cincinnati here in Southampton in studies supported by an AAIR charity PhD fellowship and MRF/Asthma UK grant. We continue our collaboration in a recently funded study by the BMA Foundation for Medical Research (2019) to study biological samples from pregnant mothers and their newborn babies collected during elective Caesarean section as part of the Maternal Environment in Pregnancy (MEP) study.
Start Year 2010
 
Description Use of Drosophila Models to Explore the Function of Asthma Susceptibility Genes 
Organisation University of Kiel
Country Germany 
Sector Academic/University 
PI Contribution Our group had the idea to use fruit flies to study different asthma susceptibility genes and provided the different plasmids of two asthma susceptibility genes ADAM33 and CDHR3, which were sent to our collaborator Professor Thomas Roeder at Christian-Albrechts-Univerity of Kiel in Germany.
Collaborator Contribution Professor Roeder is an expert in fly biology and his group made different genetically engineered ADAM33 and CDHR3 flies, which they have studied in Kiel and have also sent back to us for our experiments here in Southampton.
Impact This collaboration was part of an strategic NC3R grant with the title "Use of Drosophila models to explore the function of asthma susceptibility genes" (NC/M001482/1) from April 2015 to March 2017. This involved multidisciplinary collaboration between fly biologists, respiratory scientists and clinician scientist. A manuscript of this collaboration is in preparation. A patent application was also submitted for the use of genetically modified Drosophila line carrying one or more mammalian genes associated with a chronic respiratory disease, and uses of the genetically modified line for therapeutic agent screen in 2018.
Start Year 2015
 
Title ANTI-ADAM33 OLIGONUCLEOTIDES AND RELATED METHODS 
Description The present disclosure provides antisense compounds, methods, and compositions for silencing ADAM33 mRNA. The present disclosure provides antisense compounds, methods, and compositions for the treatment, prevention, or amelioration of diseases, disorders, and conditions associated with ADAM33 in a subject in need thereof. Also contemplated are antisense compounds and methods for the preparation of a medicament for the treatment, prevention, or amelioration of a disease, disorder, or condition associated with ADAM33. 
IP Reference EP3599844 
Protection Patent application published
Year Protection Granted 2020
Licensed No
Impact Based on this patent we were able to start informal and formal conversations with interested investors with the aim to start a spin-out or licence agreement.
 
Title ANTI-ADAM33 OLIGONUCLEOTIDES AND RELATED METHODS 
Description The present disclosure provides antisense compounds, methods, and compositions for silencing ADAM33 mRNA. The present disclosure provides antisense compounds, methods, and compositions for the treatment, prevention, or amelioration of diseases, disorders, and conditions associated with ADAM33 in a subject in need thereof. Also contemplated are antisense compounds and methods for the preparation of a medicament for the treatment, prevention, or amelioration of a disease, disorder, or condition associated with ADAM33. 
IP Reference US2019002885 
Protection Patent application published
Year Protection Granted 2019
Licensed No
Impact N/A
 
Title ANTI-ADAM33 OLIGONUCLEOTIDES AND RELATED METHODS 
Description The present disclosure provides antisense compounds, methods, and compositions for silencing ADAM33 mRNA. The present disclosure provides antisense compounds, methods, and compositions for the treatment, prevention, or amelioration of diseases, disorders, and conditions associated with ADAM33 in a subject in need thereof. Also contemplated are antisense compounds and methods for the preparation of a medicament for the treatment, prevention, or amelioration of a disease, disorder, or condition associated with ADAM33. 
IP Reference WO2018226788 
Protection Patent application published
Year Protection Granted 2018
Licensed No
Impact Based on this patent we have been able to enter informal and formal discussion with potential investors with the aim to start a spin-out or licence our IP.
 
Title THERAPEUTIC AGENT SCREEN 
Description The present invention describes a genetically modified Drosophila line carrying one or more mammalian genes associated with a chronic respiratory disease, and uses of the genetically modified line. 
IP Reference WO2018104753 
Protection Patent application published
Year Protection Granted 2018
Licensed No
Impact N/A
 
Title Therapeutic agent screen 
Description Applicant: The University of Southampton, Inventors: Donna E DAVIES, Jane E COLLINS, Hans Michael HAITCHI, Thomas, ROEDER, Amripal M WASANTHA The present invention describes a genetically modified Drosophila line carrying one or more mammalian genes associated with a chronic respiratory disease, and uses of the genetically modified line. 
IP Reference WO2018104753 
Protection Patent granted
Year Protection Granted 2018
Licensed No
Impact N/A
 
Description 5-minute pitch about our ADAM33 asthma research at FutureWORLDS Southampton event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact FutureWORLDS Southampton is University of Southampton initiative to bring industry together with science.
I was invited for a 5-minute presentation of our ADAM33 asthma research and Q&A for a 'Pitch for Partnership in Immunology' to industry in July 2018.
This was a publicly advertised event attended by members of the public.
Year(s) Of Engagement Activity 2018
URL https://futureworlds.com
 
Description AAIR Charity Summer Fair 2013 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Talking about my asthma research (funded by the MRC and AAIR charity) with people from the public sparked questions: some of them related to my asthma research, some of the of clinical nature about themselves or friends or relatives who suffer from asthma. Some people also wanted to find out how they could support our local/regional research.

This resulted of one of my team to be invited to give a short presentation about asthma and her research at the Summer fest of the Brune Park School in Gosport in July 2014.
Year(s) Of Engagement Activity 2013
 
Description AAIR charity yearly memorial christmas service 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Between 10 and 30 people attended this memorial service in memory of patients who died off asthma and in support of their families who often support the AAIR charity and our research.
After the service there is always a short reception with minced pies and drinks which enables researchers to engage and interact with the visitors and answer questions about our asthma research.
Year(s) Of Engagement Activity 2013,2014,2015,2016
URL http://www.aaircharity.org
 
Description Asthma: Protein all mögliche Ursache 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was a short news report about our publication in the "Österreichische Ärztezeitung" (a magazine for Austrian medical doctors) together with the press release by the University of Southampton the "Austria Presse Argentur" in connection with our publication in The Journal of Clinical Investigation - Insight with the title: Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life in 2016.
Year(s) Of Engagement Activity 2016
URL http://www.aerztezeitung.at/archiv/oeaez-2016/oeaez-1516-15082016/medizinische-kurzmeldungen-hiv-mer...
 
Description BMA Foundation for Medical Research award ceremony 12Nov2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Supporters
Results and Impact On 12 November 2019 my colleague Matthew Coleman and I were awarded an James Trust asthma research grant by The British Medical Association Foundation for Medical Research. At the awards ceremony with over 160 guests we were able to talk to donors, philanthropists, other researchers, parliamentarians and other charity leaders about our asthma research.
http://www.bmafoundationmr.org.uk/grant-winners-2019
This was covered in the news or the Daily Echo on the 17th November 2019.
https://www.dailyecho.co.uk/news/18041810.two-southampton-doctors-given-65-000-funding-towards-asthma-research/
Year(s) Of Engagement Activity 2019
URL http://www.bmafoundationmr.org.uk/grant-winners-2019
 
Description Cover of our BMA award in Daily Echo 17Nov2019 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact On 12 November 2019 my colleague Matthew Coleman and I were awarded an James Trust asthma research grant by The British Medical Association Foundation for Medical Research.
This was covered in the news or the Daily Echo on the 17th November 2019.
https://www.dailyecho.co.uk/news/18041810.two-southampton-doctors-given-65-000-funding-towards-asthma-research/
Year(s) Of Engagement Activity 2019
URL https://www.dailyecho.co.uk/news/18041810.two-southampton-doctors-given-65-000-funding-towards-asthm...
 
Description Dani King dinner 2013 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Supporters
Results and Impact About hundred people attended this evening programme together with dinner with our Olympian gold medalist Dani King on the 11th April 2013. The dinner was sponsored by DC Employment Solicitors and an auction was conducted by BBC's Graham Barton to raise funds for the AAIR charity. I was invited to give a short talk about my MRC and AAIR charity funded asthma research in Southampton. After dinner this gave me the opportunity to interact with many guests of the evening and to answer many asthma and research related questions.

The dinner guests generously participated in the auction for the benefit of the AAIR charity. Some of the guests made enquires how they could get involved in asthma research, such as volunteers for asthma research.
Year(s) Of Engagement Activity 2013
URL http://www.aaircharity.org
 
Description Film shot about our ADAM33 asthma research by the British Medical Association Foundation for Medical Research 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Supporters
Results and Impact The British Medical Association Foundation for Medical Research shot a film about our research in our laboratory for an Awards Ceremony in November 2018. Over 160 guests who watched the film attended the event. This included donors, philanthropists, other researchers, parliamentarians and other charity leaders.
YouTube: https://www.youtube.com/watch?v=sEhhshEK4sw
Vimeo: https://vimeo.com/299438228
Year(s) Of Engagement Activity 2018
URL https://www.youtube.com/watch?v=sEhhshEK4sw
 
Description Gero's IMR: ADAM33-Gen könnte Asthma stoppen 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact This was a full report in the Gerontological-Economic Research Organisation's report of the "GERO's Internationaler Medizin-Report" Number 11, Nov 2016 in response to the press release by the University of Southampton in connection with our publication in The Journal of Clinical Investigation - Insight with the title: Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life in 2016.
Year(s) Of Engagement Activity 2016
URL http://gero.org/5/gero?&wslanguage=en
 
Description Interview, filming and photo shots for Asthma UK 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Supporters
Results and Impact In June 2019 Asthma UK came to interview me and do some filming and photo shots in our laboratory that were used for the Asthma UK webpage and fundraising.
Asthma UK webpage: https://www.asthma.org.uk/treatment-support-research/
You Tube: https://www.youtube.com/watch?v=ZKxmiswmAQw
Year(s) Of Engagement Activity 2019
URL https://www.asthma.org.uk/treatment-support-research/
 
Description LifeLab Meet the Scientist Training 2014 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact *Be able to identify key points of my own Asthma & ADAM33 research, which will generate discussion amongst teenagers
*Be able to communicate my research story effectively to different audiences - with some
appreciation of how to modify for different audiences
*Be able to facilitate a discussion about my research amongst teenagers
*To build up my skills needed for this facilitation - confidence in own communication skills,
questioning skills, listening skills
*To build up confidence in dealing with school students and the different scenarios which might
arise!

I was invited to take part in a public engagement event -lung health funded by NC3Rs and was awarded to highlight our human based models of the airways to the public in our Faculty of Medicine LifeLab on 17th November 2014
This event is
I was also invited to take part in 'meet the scientist' sessions for school students in our LifeLab in December 2014.
Year(s) Of Engagement Activity 2014
URL http://www.southampton.ac.uk/lifelab
 
Description Live Broadcast: Shaun Doherty Show - Highland Radio in Ireland: ADAM33 and asthma. 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact This was a live interview at the Shaun Doherty Show at Highland Radio, a local radio station in Irland, in response to the press release by the University of Southampton in connection with our publication in The Journal of Clinical Investigation - Insight with the title: Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life in 2016.
Year(s) Of Engagement Activity 2016
URL http://www.highlandradio.com/shaun-doherty/
 
Description MRC network magazine: Controlling ADAM33 gene could stop asthma 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact This was a short summary of our research outcome for the Medical Research Council (MRC) in their news section of the network magazine together with the press release by the University of Southampton in connection with our publication in The Journal of Clinical Investigation - Insight with the title: Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life in 2016.
Year(s) Of Engagement Activity 2013,2016
URL https://www.mrc.ac.uk/news/browse/controlling-adam33-gene-could-stop-asthma/
 
Description MRF trustees and staff meeting and MRC Fellows' Symposium May 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact In May 2018 & June 2019 I attended an MRF trustees and staff evening meeting. This gave me the opportunity to interact with MRF trustees and staff and explain our ADAM33 and asthma research to them.
At the MRC Fellows' Symposium on the following day I was able to attend a very helpful special break out session about 'Pitching your ideas' by Simon Cain. I learned how to best present our research and ideas to different public and lay audiences.
Year(s) Of Engagement Activity 2018,2019,2020
 
Description New study to assess why 'rogue gene' causes asthma in early life 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact The press release by the University of Southampton about our new Medical Research Foundation/Asthma UK study with the title "The impact of pre- and perinatal ADAM33 induced airway remodeling on sensitivity to environmental challenges and the early life development of asthma" was picked up by MedicalXpress as part of Science X™ that is a leading web-based science, research and technology news service.
Year(s) Of Engagement Activity 2016
URL https://medicalxpress.com/news/2016-03-rogue-gene-asthma-early-life.html
 
Description Online interview: Loss of ADAM33 suppresses features of asthma, suggesting targeting ADAM33 as a potential new asthma therapy 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact This was a online interview with Medical Research.com, an international web-based Medical News platform, in response to the press release by the University of Southampton in connection with our publication in The Journal of Clinical Investigation - Insight with the title: Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life in 2016.
Year(s) Of Engagement Activity 2016
URL https://medicalresearch.com/author-interviews/loss-adam33-suppresses-features-asthma-suggesting-targ...
 
Description Personal webpage www.carrotbird.com about my woodworking hobby with information about my asthma research 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact After my medical doctor training I completed my apprenticeship exam for carpentry and joinery in 1991.
Therefore, I have love for working with wood and as a hobby and relaxation from work I started making wooden bendy fish and other wooden toys and art.
Initially this was mainly as presents or gifts for family, but now I also make wooden art work on commission.
A proportion of any sales goes toward my asthma research to the charities that support my research work.
Local, national or international people who are interested or commission some of my woodwork often show also great interest in my asthma research.
This gives me the opportunity to explain about my research into the asthma gene ADAM33 and its role in the development of asthma.
Year(s) Of Engagement Activity 2018,2019
URL http://www.carrotbird.com
 
Description Press release: New study to assess why 'rogue gene' causes asthma in early life 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact This press release about new grant from Medical Research Foundation/Asthma UK with the title: The impact of pre- and perinatal ADAM33 induced airway remodeling on sensitivity to environmental challenges and the early life development of asthma. This was picked up by some local and national media.
Year(s) Of Engagement Activity 2016
URL http://www.southampton.ac.uk/news/2016/03/rougue-asthma-gene-study.page
 
Description Press release: Stop the rogue ADAM gene and you stop asthma. 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact This press release was send out by the University of Southampton in connection with our publication in The Journal of Clinical Investigation - Insight with the title: Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life in 2016.
This publication has made a significant contribution to our understanding how soluble ADAM33 initiates airway remodelling, which promotes susceptibility for allergic asthma in early life and the press release has attracted wide attention by national and international media and the scientific community (Australia, Austria, Belgium, India, Ireland, USA, UK, ...).
The Article was covered over 100 times in the media: in local newspapers (southern Daily Echo) and all national newspapers (The Independent, The Daily Telegraph, The Daily Mirror, The Sun, ...)in the UK and even in international newspapers (Business Standard India, ...). Additionally it was covered by engagement focused websites, bogs and social media channels, local radio and TV stations and national radio stations.
Year(s) Of Engagement Activity 2016
URL http://www.southampton.ac.uk/news/2016/07/adam-33-gene.page
 
Description Quarterly Wessex Asthma Network meetings 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact At our local quarterly Wessex Asthma Network meetings I have been able to talk about my asthma research to patients
with asthma, industry, professional practitioners, post-graduate students, study participants, who attend these meetings.
Year(s) Of Engagement Activity 2015,2016,2017,2018,2019,2020
URL http://wessex-asthma.com
 
Description Radio broadcast: Wave 105: Rogue gene could be key to preventing asthma. 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact This was a recorded interview for Radio Wave 105.2, a local radio station, in response to the press release by the University of Southampton in connection with our publication in The Journal of Clinical Investigation - Insight with the title: Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life in 2016.
Year(s) Of Engagement Activity 2016
URL https://www.facebook.com/Wave105/posts/1114652868570857
 
Description Summerfest at Brune Park School in Gosport 2014 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Dr Lizzie Davies from my team spoke about the asthma research work being carried out at Southampton General Hospital and supported by the MRC and AAIR charity.

Some 450 pupils in Fonteyn House at Brune Park School have chosen the Asthma, Allergy and Inflammation Research Charity (AAIR) as their fund raising project for the year.
Year(s) Of Engagement Activity 2014
URL http://www.aaircharity.org/category/fundraising-news/
 
Description That's Solent TV: Southampton Scientists Discover Potential Way Of Reducing The Symptoms of Asthma 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact This was a filmed and recorded interview for That's Solent TV, a local TV station, in response to the press release by the University of Southampton in connection with our publication in The Journal of Clinical Investigation - Insight with the title: Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life in 2016.
Year(s) Of Engagement Activity 2016
URL https://www.youtube.com/watch?v=Ei7lW-7fRGw
 
Description Winchester High-street Christmas Market 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I am also a trained joiner and my hobby is wood working and I make wooden artwork in form of fish, cars and bottle openers, which I sold on a vendor's tray and with a pedlar's certificate in the high-street of Winchester before Christmas on Saturdays and Sundays in December 2017 . A certain part from the sale of my artwork goes to charitable work e.g. charities that support my research (AAIR, Asthma UK) and christian charities (Christians Against Poverty, Basic food banks). This new endeavour to me gave me the opportunity to speak to many people and explain to them what I do as my hobby, but also to talk about my research into the role of the asthma gene ADAM33.
Year(s) Of Engagement Activity 2017