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The University of Southampton
Medicine
Phone:
(023) 8120 8410
Email:
H.M.Haitchi@soton.ac.uk

Dr Hans Michael Haitchi MD, MMed (INT), PhD, PD, MRCP (London), FHEA, PGcert

Associate Professor in Respiratory Medicine & Clinician Scientist, NHS Honorary Consultant Physician,Lead of NIHR SBRC Respiratory Clinical Studies Forum (CSF)

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Dr Hans Michael Haitchi is an Associate Professor in Respiratory Medicine & Clinician Scientist within the Faculty of Medicine at the University of Southampton and Honorary Consultant Physician in University Hospital Southampton NHS Foundation Trust.

Having graduated with a Doctor of Medicine in 1990 he trained as an Emergency Physician and General Practitioner in Austria.  In 1996 he moved to South Africa where he completed his specialist training in Internal Medicine with a special interest in Pulmonary Medicine at Tygerberg Hospital, Cape Town in 2001. He also graduated with a Master in Medicine (Internal Medicine) in 2020. Coming as Clinical Research Fellow to Southampton in England in 2001 he completed his Doctor of Philosophy in Molecular Biology in 2008 and his Postgraduate Certificate in Education in 2009 and became a Fellow of the Higher Education Academy (FHEA). He holds an affiliate membership of the Royal College of Physicians since 2011 and was awarded the title of ‘Privatdozent’ for Pneumology at the Private Medical University Salzburg, Austria in 2014.

 Hans Michael Haitchi held a Medical Research Council (MRC) Clinician Scientist Fellowship from 2010 to 2014 in the Faculty of Medicine at the University of Southampton.  This MRC fellowship took him from 2010-2011 to the USA, where he did research as a visiting scientist and scholar in Professor Whitsett's pulmonary biology lab in Cincinnati Children's Hospital Medical Center.

 Back in Southampton, Dr. Haitchi leads a group that investigates the pathogenesis of asthma and other chronic lung diseases. His particular interest is in the role of the asthma susceptibility gene ADAM33 in asthma and influence of the maternal environment on the early origin of lung disease using in vivo and in vitro asthma and allergic airway inflammation research models. A further related interest is developing novel Anti-ADAM33 agents as potential disease modifying asthma treatment.

His research is based in the Faculty of Medicine and NIHR Southampton Biomedical Research Centre Respiratory theme, where he is a principle investigator.

Qualifications

DM, University of Graz, Austria 1990
MMed (INT), University of Stellenbosch, South Africa 2000
PhD, University of Southampton, UK 2008
PGcert, University of Southampton, UK 2009
MRCP (London), Royal College of Physicians, 2011
PD, Priv. Doz., Paracelsus Medical University (PMU) Salzburg, Austria 2014 

Appointments held

Research Fellow, AVL Medical Instruments, Graz, Austria, 1991
Military assistant medical doctor, Federal Ministry of Defence, Austria, 1991-1992
House and Medical Officer, Private Hospital “Barmherzige Brüder” and University Hospital Graz, Austria, 1992-1995
Registrar (Clinical assistant), Stellenbosch University Hospital Tygerberg, Department of Internal Medicine, Cape Town, South Africa, 1996-2001
Clinical Research Fellow, Division of Infection, Inflammation & Repair, School of Medicine, University of Southampton, UK, 2001-2009
Honorary Consultant Physician in Medicine & Respiratory Medicine, Southampton University Hospital NHS Foundation Trust, UK, 2009-present
Visiting Scientist and Scholar, Cincinnati Children’s Hospital Medical Center, College of Medicine, University of Cincinnati, US, 2010-2011
MRC Clinician Scientist, Faculty of Medicine, University of Southampton, UK 2010 - 2014
Senior Lecturer in Respiratory Medicine, Faculty of Medicine, University of Southampton, UK 2011 - 2014
Associate Professor in Respiratory Medicine & Clinician Scientist, Faculty of Medicine, University of Southampton, UK 2014-present

Research interests

Dr. Haitchi’s research focuses on chronic lung diseases, such as asthma and COPD, which are a major burden on the healthcare system in the UK and worldwide. Many of these diseases originate early in life by an interaction between parental genetic and environmental factors (e.g. maternal allergy & smoking) before birth and in infancy. From epidemiological studies it is known that these early interactions predict if somebody develops a chronic lung disease later in life, however very little is known about the exact mechanisms or how this occurs. By exploring these mechanisms his ultimate aim is to find and develop novel therapies that act early as well as later in life..

Fig1 ADAM33 Gene Environment Interactions in Developing Lungs and their Involvement in the Early Origin of Asthma.

Dr. Haitchi’s research focuses on chronic lung diseases, such as asthma and COPD, which are a major burden on the healthcare system in the UK and worldwide. Many of these diseases originate early in life by an interaction between parental genetic and environmental factors (e.g. maternal allergy & smoking) before birth and in infancy. From epidemiological studies it is known that these early interactions predict if somebody develops a chronic lung disease later in life, however very little is known about the exact mechanisms or how this occurs. By exploring these mechanisms his ultimate aim is to find and develop novel therapies that act early as well as later in life.

 In 2002 the group in Southampton in collaboration with two groups in the US discovered ADAM33 as an Asthma susceptibility gene. Small changes in the gene make people more prone to develop asthma or COPD and are associated with an increased decline in lung function in children and adults. The protein that is made by the gene is normally found in the membrane on the surface of a cell.

Dr. Haitchi reported that ADAM33 is almost exclusively expressed in structural airway cells (such as smooth muscle cells, fibroblasts, myofibroblasts, and mesenchymal progenitor cells, but not epithelial cells) (AJRCCM 2005, JACI 2008). This suggests that ADAM33 is involved in the remodelling of the airways that take place in asthma (thicker walls, more muscles, more vessels, more fibrotic tissue and more mucus producing cells).

Epithelial-derived TGF-β induces shedding of a ‘rogue’ form of the membrane anchored ADAM33 protein from the cell surface (JACI 2019) resulting in a short soluble protein form of ADAM33 (sADAM33) that acts as an active enzyme and can cleave other proteins. This enzymatically active sADAM33 protein is increased in patients with asthma with impaired lung function (gain of function) (JCI 2016) and it can induce the formation of new blood vessels in the lung (JACI 2008). 

 Furthermore, Dr Haitchi’s group reported how ADAM33 functions as a local tissue susceptibility gene for asthma.  Their findings suggest that sADAM33 induces airway remodeling independent of inflammation. They showed that human sADAM33 induces airway remodeling in human and murine lungs in early life, which enhances allergic responses to low concentrations of allergen to produce asthma-like features - findings that help explain the increased susceptibility of asthmatic individuals to environmental allergens. Since sADAM33 is induced in utero by maternal allergy (JACI 2009), their findings may explain why airway remodeling and bronchial smooth muscle are increased in the airways of young children who subsequently progress to develop asthma.

 Dr Haitchi’s group proposes a new paradigm in which (p)remodeled airways provide the ‘soil’ for allergic inflammation in susceptible individuals leading to Type 2 allergic airway inflammation and BHR that characterizes asthma.   They also showed that inflammation and remodeling are both suppressed in Adam33 null mice and that airway (p)remodeling is reversible when sADAM33 is arrested in developing lungs (JCI 2016), identifying sADAM33 as a novel target for disease modifying therapy in asthma (TV Solent).

In collaboration with Jonathan Watts at the RNA Therapeutics Institute at the University of Massachusetts Medical School they discovered that the asthma susceptibility gene ADAM33 can be readily silenced by LNA gapmer antisense oligonucleotides (MTNA 2017, Patent WO2018226788), which they are currently developing as a new anti-remodelling therapy in asthma and other ADAM33 associated lung diseases.

The research aims of Dr. Haitchi’s group are to better understand the role of ADAM33 in asthma and to study the influence of maternal environmental factors during pregnancy on ADAM33 and development of asthma and other chronic lung diseases in childhood and later in life (Asthma UK Video, BMA Video). The ultimate aim is to develop a novel anit-ADAM33 and anti-remodelling and disease modifying asthma treatment.

His group pursues this using the following approaches:

1. Study of airway remodelling and allergic airway inflammation in asthma using different transgenic in vivo and ex vivo models.

2. Study of the influence of an allergic maternal environment using different in vivo, ex vivo and in vitro models (collaborations with Jeff Whitsett, Cincinnati Children’s Hospital Medical Center & David Bassett, Wayne State University, Detroit, US)

3. Development and study of novel and specific ADAM33 inhibitors (collaboration Jonathan Watts, University of Massachusetts Medical School, Worcester, USA).

4. Study of the impact of maternal allergic asthma during pregnancy on asthma related mediators including ADAM33 in biologic samples collected during caesarean sections using a multiomic approach (proteomics and RNA-Seq; collaboration with Professors Jeff Whitsett and Assem Ziady from Cincinnati Children’s Hospital Medical Center, USA and Dr Rob Ewing from Proteomics and Systems Biology at the University of Southampton) as part of the Maternal Environment in Pregnancy (MEP) study (PI: HMH and co-PI: Dr Matthew Coleman, an obstetrician in maternal and fetal medicine at University Hospital Southampton).

5. Wessex AsThma CoHort of Difficult Asthma (WATCH): A Pragmatic Real-Life Longitudinal Study of Difficult Asthma in the Clinic (PI: Ramesh J Kurukulaaratchy, Co-PI: HMH).

6. Study of human asthma, COPD, cystic fibrosis, interstitial lung disease in patient derived samples (collaborations with Graham Roberts, Julian Legg, Peter Howarth, Ben Marshall Southampton NIHR Respiratory Biomedical Research Units, University Hospital Southampton, UK; Michael Studnicka, Univ. Klinik für Pneumologie, Paracelsus Private Medical School Salzburg, Austria; Grazina Kwapiszewska, Leigh Marsh & Andrea Olschewski, Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria)

His research has been funded by: Asthma Allergy & Inflammation Research (AAIR), Asthma UK, British Lung Foundation (BLF), British Medical Association, Engineering and Physical Sciences Research Council (EPSRC), Medical Research Council (MRC), Medical Research Foundation (MRF), National Centre for the Replacement Refinement and Reduction of Animals in Research (NC3Rs), Research Management Committee – Faculty of Medicine – University of Southampton, Roger Brooke Charitable Trust, Wessex Medical Research.

 
Gene Environment Interactions in Developing Lungs and their Involvement in the Early Origin of Asthma.
Fig1 ADAM33

Department(s)

Clinical and Experimental Sciences

Affiliate Department(s)

Respiratory and allergy Research group

Postgraduate students supervision

2007 Gemma Campbell Harding* (MRes)
2007 Shelley Davis* (MRes)
2010 Antonio Noto* (PhD)
2010-2014 Elizabeth R. Davies (PhD) as a main supervisor
2011-2017 Nick Udell (PhD) as co-supervisor with Philipp Thurner, Faculty of Engineering & the Environment).
2013-2017 Romana Mikes (PhD) as co-supervisor with Michael Studnicka, Paracelsus Private Medical School Salzburg, Austria
2014-2018 Joanne F C Kelly (Integrated PhD) as a main supervisor
2016-2020 Marieke Wandel (PhD) as main supervisor

Faculty of Medicine

Member of the Allergy & Respiratory Research Board, 2011 – 

University of Southampton

Member of Senate, 2013 – 2016 

University Hospital Southampton NHS Foundation Trust

Honorary Consultant Physician in Difficult Airways Disease Clinic, 2009 –

Lead of Young Asthma Patient Clinic (Transitional Asthma Service), 2009 –

Member of the University Hospital Southampton NHS Foundation Trust Asthma Allergy and Clinical Immunology (AACI) Consultant team, 2011 –

Member of interview panel for Academic Clinical Fellowship (ACF) posts at Wessex Deanery, 2015 – 

NIHR Southampton Biomedical Research Centre (SBRC)

Member of NIHR SBRC Respiratory & Critical Care management board, 2017 –

Lead of NIHR SBRC Respiratory Clinical Studies Forum (CSF), 2017 – 

National and International responsibilities

Visiting Scientist and Scholar, Cincinnati Children’s Hospital Medical Center, College of Medicine, University of Cincinnati, US, 2010 –

Privatdozent’ (PD, Priv. Doz.) for Pneumology at the Paracelsus Medical University (PMU) in Salzburg Austria, 2014 –

Member of European Cooperation in Science and Technology (COST) Action BM1201, Developmental Origins of Chronic Lung Disease, 2011 –

Trustee/Director of Medical Research Foundation (MRF), London, UK, 2020 –

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Articles

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Conferences

Letter/Editorial

Patent

Postgraduate Students

MD thesis examiner

Integrated PhD

MRes project supervisor and examiner
IPhD main supervisor

Bachelor of Medicine (BM) Programme 5

Tutor and marker of assignments in Cardiopulmonary Systems Course:  Year 1 students
Marker of assignments: Year 3 students.
Project supervisor: Year 4 students in depth & intercalated BSc.

BM5/BM (EU)

Coordinator of Scientific Basis of Medicine (SBOM) for Respiratory Medicine: Year 3 students.

Nuffield Science School and Colleges Bursaries

Project supervisor

British Science Association: Creativity in Science and Technology (CREST)

Mentor

 

Research Projects

2003 – 2006    The Role of ADAM33, a Novel Asthma Susceptibility Gene, in Embryonic Lung Development, British Lung Foundation Project Grant. £ 107,000

2006               ADAM33 in COPD, Roger Brooke Charitable Trust Grant. £ 109,000

2006                ADAM33 in lung development. Roger Brooke Charitable Trust Personal Fellowship. £ 45,000 

2010 – 2014    ADAM33 Gene Environment Interactions in Developing Lungs and their Involvement in the Early Origin of Asthma. MRC Clinician Scientist Fellowship. G0802804; £1,035,126 

2012    Novel oligonucleotides and conjugates for asthma research and therapy. Institute for Life Sciences, University of Southampton, EPSRC Bridging the Gap Grant (collaboration with Jonathan K Watts, Department of Chemistry, UoS). £9,658 

2014    The role of ADAM33 in pre- and perinatal airway remodelling and the early life development of asthma.  Stephen T Holgate PhD studentship, Allergy & Inflammation Research (AAIR) Charity, UK. £106,200 

2016 – 2019    The impact of pre- and perinatal ADAM33 induced airway remodeling on sensitivity to environmental challenges and the early life development of asthma. Medical Research Foundation (MRF)/Asthma UK Research Grant (Asthma UK Video), MRFAUK-2015-322. £ 291,756 

2018 – 2019    The role of EGFR inhibition in Corticosteroid-Resistant Neutrophilic Airway Inflammation Caused by IL-13. Asthma, Allergy & Inflammation Research (AAIR) Charity, UK Grant. £10,975 

2018 – 2021    The impact of the asthma gene, ADAM33, on innate immunity and susceptibility to allergic airways inflammation. BMA Foundation for Medical Research: Jon Moulton Asthma Research grant (BMA Video), UK: £64,300 

2019 – 2020    Prevention and treatment of allergic asthma in vivo using ADAM33 silencing oligonucleotides. MRC Confidence in Concept grant, University of Southampton, UK: £42,378 

2019 – 2022    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. BMA Foundation for Medical Research: The James Trust for research into asthma, UK: £64,954 

2019 – 2022    Optimizing ADAM33-targeted ASOs for clinical development for asthma and COPD. UMass Bridge funding with collaborator Jonathan Watts from RNA Therapeutics Institute, University of Massachusetts, USA: $ 188,000

Clinical studies

2019 –             Investigation of the influence of the Maternal Environment in Pregnancy (MEP) on the unborn child and the development of lung disease such as asthma inearly life.  REC reference: 19/LO/0175, Protocol number: RHM O&G 0268, IRAS project ID: 256458 Principal Investigator: HM Haitchi, Co-investigators: M Coleman, J Forbes, B Van Rijn 

2015 –             Wessex AsTHma CoHort of difficult asthma (WATCH) A Longitudinal Cohort Study to Facilitate Better Understanding and Management of Difficult Asthma Encountered in Clinical Practice. REC reference: 14/WM/1226, Protocol number: RHM MED 1216 Principal Investigator: RJ Kurukulaaratchy, PH Howarth, Co-investigators: P Dennison, T Wilkinson, HM Haitchi, R Djukanovic, A Chauhan.

Dr Hans Michael Haitchi
Faculty of Medicine, University of Southampton, Level F, South Block, MP810, Tremona Road, Southampton SO16 6YD, UK.

Room Number: SGH/LF101/MP810

Telephone:(023) 8120 8410
Email:H.M.Haitchi@soton.ac.uk

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