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Professor Ratko Djukanovic MD, DM, FRCP

Professor of Medicine, Director of the Southampton NIHR Respiratory Biomedical Research Unit,Director of the NIHR Southampton Centre for Biomedical Research

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Professor Ratko Djukanovic is Professor of Medicine within Medicine at the University of Southampton.

Professor Djukanovic was appointed Professor of Respiratory Medicine at the University of Southampton in 2004 and promoted to Professor of Medicine in 2011. He has held several senior positions at the University of Southampton, including Directorship of the Division of Infection, Inflammation and Immunity and he oversaw the merger of this Division with the Division of Clinical Neurosciences, forming the new Clinical and Experimental Sciences department. 

Professor Djukanovic is the Director of the National Institute for Health Research Respiratory Biomedical Research Unit (NIHR RBRU) (www.uhs.nhs.uk/nihr-bru) and Director of the Southampton Centre for Biomedical Research (SCBR) (www.clinicalresearchinsouthampton.uhs.nhs.uk. He is also Chairman of the Steering Committee of the UK Translational Research Partnership in Inflammatory Respiratory Diseases supported by NIHR (http://www.nocri.nihr.ac.uk/resources/resources).

The Southampton NIHR RBRU unit was one of three Respiratory BRUs founded in 2008, receiving £6.55 million to support a programme of translational research in major respiratory diseases across the life-course. Together with additional funds from the Department of Health, the University Hospital Southampton NHS Foundation Trust and the University of Southampton enabled the creation of the SCBR, comprising 4,000 m2 of clinical and laboratory space dedicated to multidisciplinary translational research activities. The SCBR was opened by the Secretary of State for Health and the Chief Medical Officer, Professor Dame Sally Davies in March 2011.

Professor Djukanovic leads the Inflammatory Cell Biology Group, comprising both clinical and non-clinical scientists, including postgraduate students. The group focuses on the role of inflammatory cells (T cells, dendritic cells, macrophages and neutrophils) in asthma and chronic obstructive pulmonary disease (COPD). His team uses (bronchial and parenchymal) lung explant models to investigate inflammatory and remodelling mechanisms caused by allergens and viruses and applies these in proof of concept studies of novel drugs. Professor Djukanovic also heads the severe asthma biomarker discovery programme in Southampton using proteomic and lipidomic methods, largely funded by the U-BIOPRED (UnbiasedBIOmarkers for the Prediction of REspiratoryDisease Outcomes), a €22 million programme funded by the EU Innovative Medicine Initiative (IMI)(http://www.ubiopred.european-lung-foundation.org/). Together with colleagues from the University of Amsterdam (Professor Peter Sterk) and Imperial College London (Professors Fan Chung and Ian Adcock), Professor Djukanovic is co-founder of U-BIOPRED.

Professor Djukanovic is an Honorary Consultant in Respiratory Medicine at the Southampton University Hospitals NHS Trust.

Potential students, post-doctoral scientists or clinician scientists who are interested in joining his group are encouraged to contact Professor Djukanovic.

Degree Qualifications

DM, University of Belgrade, 1978
Specialist in Internal Medicine, University of Belgrade, 1985
MSc Immunology, University of Belgrade, 1986
DM, University of Southampton, 1994

Appointments held

Assistant Professor of Internal Medicine, Medical Faculty, University of Belgrade, 1988

Research Fellow, School of Medicine, University of Southampton, 1988-1991

Visiting Registrar, Southampton General Hospital, Southampton, 1991-1992

Senior Clinical Research Fellow, School of Medicine, University of Southampton, 1992-1997

Senior Lecturer in Medicine, School of Medicine, University of Southampton, 1997-2004

Professor of Respiratory Medicine, School of Medicine, University of Southampton, 2004-present

Director of Allergy and Inflammation Research, Deputy Director, Division of Infection, Inflammation and Immunity, School of Medicine, University of Southampton, 2005-2007

Director - Division of Infection Inflammation and Immunity, 2007- 2010

Head of Infection, Inflammation and Immunity, Faculty of Medicine, University of Southampton, 2010-2011

Professor of Medicine, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, 2011-present

Director of the NIHR Southampton Respiratory Biomedical Research Unit, 2008-present

Director of the Southampton Centre for Biomedical Research, 2011-present

Research interests

Central to the research undertaken in Professor Djukanovic’s group is the use of tissue and cells obtained from the airways of volunteer patients with chronic airways disease by fibreoptic bronchoscopy (with bronchial biopsy, bronchoalveolar lavage (BAL)), resection of lung tissue during routine thoracic surgery and sputum induced by inhaled hypertonic saline.

Regulation of immune responses in allergic asthma

Allergic asthma is a common chronic inflammatory disease the prevalence of which has risen markedly since the 60s. T lymphocytes are believed to be the central orchestrating cells in asthma and traditionally this disease has been seen as being driven by effector T cells that secrete Th2-type cytokines. The research in Professor Djukanovic’s group focuses on elucidating the relative role of other T cells, including Th1 and Th17 cells, and the balance of these against regulatory T cells. Although invariant natural killer (NKT) cells, another subset of T cells, were initially proposed to be the dominant source of Th2 cytokines in severe asthma, the Inflammatory Cell Biology group’s own research has shown this not to be the case (Vijaynand et al. N Engl J Med 2007; 356; 1410-1422 . Projects funded by Asthma UK and the Marie Curie FP7 programme have focused on the role of alternatively activated macrophages and natural as well as adaptive (induced) regulatory T cells using functional assays (cell culture), flow cytometric analysis of activation markers and quantifying gene expression by polymerase chain reaction (PCR).

Elucidation of inflammatory mechanisms in the airways induced by allergen and infectious agents

The Inflammatory Cell Biology Group has optimised the use of the “Southampton Explant Model”. The model consists of endobronchial biopsies stimulated with relevant triggers (allergen, respiratory viruses (e.g. influenza) that are known to enhance airways inflammation, thereby increasing bronchial hyper-responsiveness (a cardinal feature of asthma) and, consequently, clinical symptoms. This model has been used successfully to provide proof of concept for new targets and pre-clinical efficacy of novel anti-inflammatory drugs before their safety has been established. Using this approach, the group has shown an important role for co-stimulation between effector Th2 T cells and antigen-presenting cells bearing CD28 and B7.1 or B7.2, respectively, in the generation of Th2 cytokines and T cell chemo-attractant activity. Further studies have shown that CTLA-4 fusion protein, CCR4 inhibitors and PI3Kinase inhibitors are effective at inhibiting pro-inflammatory responses in the lung explants. Such studies are providing the pharmaceutical industry with information that assists decisions about proceeding into first in man studies with candidate drugs.

Biomarkers of chronic airways diseases

The group has a large programme to identify of biomarkers of airways disease. It was the first to apply an unbiased, proteomics approach based on 2-D gel electrophoresis and mass spectrometry of differentially expressed protein spots in gels to demonstrate that the concentrations of lipocalin and apolipoprotein are reduced in COPD and that this correlates with reduced lung function measurements. This programme, funded by an NIH grant (RO1-HL 72356-01), is now being pursued using, multiple reaction monitoring (MRM) a non-gel based method to elucidate further the role of these biomarkers. The biomarker research has since then extended into a programme aiming better to phenotype asthma through the UBIOPRED programme (http://www.ubiopred.european-lung-foundation.org/) funded by the Innovative Medicines Initiative (IMI) scheme. The aim of UBIOPRED is to identify biomarker profiles comprised of various types of high-dimensional clinical, pathological (from blood, sputum, bronchial biopsies) and imaging data, using an innovative systems biology approach to cluster biomarkers into distinct phenotype handprints. This stratified medicine approach aims to enable significantly better prediction of therapeutic efficacy than single or even clustered biomarkers of one data type and to identify novel targets.

 

IFNß as a novel treatment for exacerbations of asthma caused by the common cold

Research led by Professor Donna Davies reported in 2005 (Wark P. et al. J Exp Med 2005;201:937-47), demonstrated in their epithelial culture model of viral infection a deficiency of the bronchial epithelium to produce an adequate innate immune responses to rhinoviruses, thereby allowing the common cold virus to spread. Her group further showed that the addition of exogenous IFNß corrected this deficiency. Taking this observation further in collaboration with the Southampton University spin-out company, Synairgen (http://www.synairgen.com/), Professor Djukanovic led a proof of concept, multi-centre, randomised controlled phase 2 clinical trial to investigate whether nebulised IFNß, delivered as soon as asthma patients develop an upper respiratory tract viral infection, is able to prevent spread of infection to the lower airways and thus prevent or ameliorate asthma exacerbations. This trial showed beneficial effects in severe asthmatics, the very group of patients who are at risk of exacerbations when infected with respiratory viruses.

Research into efficacy and mechanisms of action of new asthma drugs

Professor Djukanovic has a long-standing interest in improving understanding of how established and new drugs for chronic airways diseases work. His pioneer studies have elucidated some of the actions of inhaled (Djukanovic R, Wilson JW, Britten KM, Wilson SJ, Walls AF, Roche WR, Howarth PH, Holgate ST. Effect of an inhaled corticosteroid on airway inflammation and symptoms in asthma. Am Rev Respir Dis 1992; 145:669-74) and oral (The effect of treatment with oral corticosteroids on asthma symptoms and airway inflammation. Djukanović R, Homeyard S, Gratziou C, Madden J, Walls A, Montefort S, Peroni D, Polosa R, Holgate S, Howarth P. Am J Respir Crit Care Med. 1997 Mar;155(3):826-32) corticosteroids, drugs that are the mainstay of asthma management, and the new biologics, inclduing anti-IgE monoclonal antibody, omalizumab (Corne J, Djukanovic R, Thomas L, Warner J, Botta L, Grandordy B, Gygax D, Heusser C, Patalano F, Richardson W, Kilchher E, Staehelin T, Davis F, Gordon W, Sung L, Liou R, Wang G, Chang T-W, Holgate ST. The effect of intravenous administration of a chimaeric anti-IgE antibody on serum IgE levels in atopic subjects - efficacy, safety and pharmacokinetics. J Clin Invest 1997; 99:879-887another reference: Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma. Djukanović R, Wilson SJ, Kraft M, Jarjour NN, Steel M, Chung KF, Bao W, Fowler-Taylor A, Matthews J, Busse WW, Holgate ST, Fahy JV. Am J Respir Crit Care Med. 2004 Sep 15;170(6):583-93.) and anti-IL-5 monoclonal antibody, mepolizumab (Leckie MJ, ten Brinke A, Khan J, Diamant Z, O Connor BJ, Walls CM, Mathur AK, Cowley HC, Chung KF, Djukanovic R, Hansel TT, Holgate ST, Sterk PJ, Barnes PJ. Effects of an interleukin 5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000; 356: 2144-2148). Professor Djukanovic is using his expertise in drug development as Chairman of the NIHR Translational Research Partnership (TRP) (http://www.nocri.nihr.ac.uk/resources/resources), comprising nine UK centres of excellence, selected to work together based on a unique breadth of expertise and proven ability to deliver in experimental medicine and translational research.

http://www.uhs.nhs.uk/ContactUs/Directoryofconsultants/Consultants-by-service/Respiratory-consultants/DjukanovicProfessorRatko.aspx

http://www.uhs.nhs.uk/ClinicalResearchinSouthampton/Our-people/Respiratory-research-people/Prof-ratko-Djukanovic,-director-of-the-NIHR-Southampton-Respiratory-Biomedical-Research-Unit.aspx

 

Department(s)

Clinical and Experimental Sciences

Affiliate Department(s)

Respiratory and allergy Research group

Research project(s)

BREATHE (Breathing Retraining for Asthma Trial of Home Exercise)

Although effective medicinal treatment exists for asthma, many people continue to have distressing symptoms and impaired quality of life. People with asthma have expressed interest in non-drug asthma treatments, particularly in breathing exercises. Several recent studies have shown benefits from a short course of breathing exercises taught by a respiratory physiotherapist for people with asthma who remained symptomatic despite usual treatment. We believe that many NHS patients could potentially benefit from these exercises, but unfortunately, there is currently not enough access to suitable trained physiotherapists able to provide such a service. We propose to provide the same breathing training programme that we have previously shown to be effective when taught 'face-to-face' by a physiotherapist in the form of a DVD, or internet download. Patients will use this in their own home at times convenient to them, in addition to their standard treatment (e.g. with inhalers). We will find out whether this type of instruction is better than the 'usual care' that is currently provided, and whether it is as good as the 'face to face' physiotherapist instruction (which is more expensive and less convenient for patients).

Postgraduate student supervision

Current students

Ben Nicholas

Kamran Tariq

Dominic Burg

Joost Brandsma

 

Local responsibilities

Faculty of Medicine

Member of the Faculty Leadership Team

National responsibilities
  • Chairman of the Steering Committee of the Translational Research Partnership for Respiratory Medicine, 2011-present
  • 1942 Club, 2006-present
  • Association of Physicians member, 2007-present
  • British Thoracic Society: Council member and member of the Training and Education Committee, 2007-2010
  • Member of the National Asthma Campaign (NAC) Task Force - Therapy Working Group, 1999-2001

  • Member of the British Thoracic Society (BTS) Research Committee, 1999-2001

International responsibilities
  • Head of the Clinical Allergy and Immunology Assembly of the European Respiratory Society (ERS), member of the ERS Executive Committee and the Scientific/Programme Committee, 2002-2005
  • American Thoracic Society, member of the programme committee of the Allergy, Immunology and Inflammation Assembly, 2002-2005
  • Assistant Editor of Respiratory Research, 2000-2002
  • Associate Editor of the European Respiratory Topic (a journal of the European Respiratory Society), 1998-2002
  • Associate Editor of the European Respiratory Journal, 2001-2008
  • Member of the Editorial Board of the American Journal of Respiratory and Critical Care Medicine, 2007-2010
  • Member of the International Advisory Board of the European Respiratory Journal, 2008–present
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Articles

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Letters/Editorials

Lecturer for the BM5

Supervisor for both first and final year students

Professor Ratko Djukanovic
Phone: +44 (0)23 8120 4195 Email: R.Djukanovic@soton.ac.uk Personal Assistant: rbru@soton.ac.uk +44 (0)23 8120 4195

Room Number: SGH/LF/MP810


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