Prof Ratko Djukanovic
MD, DM
Professor of Medicine, Honorary Consultant Respiratory Physician
Professor Djukanovic’s main interest is in asthma, its underlying pathobiological mechanisms, stratification into clinical phenotypes and endotypes, and unmet management needs. He also has a keen interest in mechanisms and treatments of severe respiratory viral infections.
Professor Djukanovic has conducted pioneer studies applying research bronchoscopy and sputum induction, leading the initial task forces which defined the use of these methods, thereby paving the way for standardised research approaches that enabled in-depth descriptions of the roles of various inflammatory cells and their mediators in asthma. He developed an explant model of asthma, consisting of bronchial biopsies placed into tissue culture, that could be stimulated ex vivo with relevant triggers, applying, as needed, novel agents not yet approved for in vivo use in human volunteers.
Professor Djukanovic has led the discovery of biomarkers using omics technology, establishing, with three colleagues from Amsterdam and Imperial College, London, a €27 million programme for severe asthma (U-BIOPRED), funded by the EU Innovative Medicines Initiative. More recently, Professor Djukanovic led the creation of the European Clinical Research Collaboration for Severe Asthma, SHARP, a collective of 29 European countries, engaging more than 300 severe asthma centres and nearly 16,000 patients.
Landmark publications:
1. Uddin M, Lau LC, Seumois G, Vijayanand P, Staples KJ, Bagmane D, Cornelius V, Dorinsky P, Davies DE, Djukanović R. EGF-induced bronchial epithelial cells drive neutrophil chemotactic and anti-apoptotic activity in asthma. PLoS One. 8(9):e72502 (2013).
2. Seumois G, Chavez L, Gerasimova A, Lienhard M, Omran N, Kalinke L, Vedanayagam M, Ganesan AP, Chawla A, Djukanović R, Ansel KM, Peters B, Rao A, Vijayanand P. Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility. Nat. Immunol. 15(8):777-88 (2014).
3. Djukanović R, Harrison T, … Monk P; INTERCIA Study Group. The effect of inhaled IFN-β on worsening of asthma symptoms caused by viral infections. A randomized trial. Am. J. Respir. Crit. Care Med. 190:145-54 (2014).
4. Adura PT, Reed E, Macintyre J……R, Beegan R, Boxall CB, Xiao C, Kebadze T, Aniscenko J, Cornelius V, Gern JE, Monk PD, Johnston SL, Djukanović R. Experimental rhinovirus 16 infection in moderate asthmatics on inhaled corticosteroids. Eur Respir. J. 43:1186-9 (2014).
5. Hinks TSC, Zhou X, Staples KJ, Dimitrov BD, Manta A, Petrossian T, Lum PY, Smith CG, Ward JA, Howarth PH, Walls AF, Gadola SD, Djukanović R. Innate and adaptive T cells in asthma: relationship to severity and disease mechanisms. J. Allergy Clin. Immunol. 136:323-33. (2015)
6. Nicholas B, Staples KJ……. Djukanović R. A novel lung explant model for the ex vivo study of efficacy and mechanisms of anti-influenza drugs. J. Immunol. 194: 6144-6154 (2015).
7. Staples KJ, Nicholas B, McKendry RT, Spalluto CM, Wallington JC, Bragg CW, Robinson EC, Martin K, Djukanović R, Wilkinson TM. Viral Infection of Human Lung Macrophages Increases PDL1 Expression via IFNβ. PLoS One. 10(3):e0121527 (2015).
8. Cooper GE, Pounce…, Christodoulides M, Djukanovic R, Wilkinson TM, Staples KJ. Viral Inhibition of Bacterial Phagocytosis by Human Macrophages: Redundant Role of CD36. PLoS One. 11(10):e0163889 (2016).
9. Lefaudeux D, De Meulder B,…. Djukanovic R, Auffray C, Chung KF; U-BIOPRED Study Group. U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics. J. Allergy Clin. Immunol. doi: 10.1016/j.jaci.2016.08.048 (2016).
10. Bigler J, Boedigheimer M, … Djukanovic R. A Severe Asthma Disease Signature from Gene Expression Profiling of Peripheral Blood from U-BIOPRED Cohorts. Am. J. Respir. Crit. Care Med. 195(10):1311-20 (2017).
11. Nicholas B, Dudley S,… Djukanovic R. Susceptibility to influenza virus infection of bronchial biopsies in asthma. J. Allergy Clin. Immunol. 140(1):309-12 (2017).
12. Hekking PP, Loza MJ… Djukanovic R, Sterk PJ; U-BIOPRED Study Group. Transcriptomic gene signatures associated with persistent airflow limitation in patients with severe asthma. Eur. Respir. J. 27;50(3) (2017).
13. Hilvering B, Hinks TSC, Stöger L, Marchi E, Salimi M, Shrimanker R, Liu W, Chen W, Luo J, Go S, Powell T, Cane J, Thulborn S, Kurioka A, Leng T, Matthews J, Connolly C, Borg C, Bafadhel M, Willberg CB, Ramasamy A, Djukanović R, Ogg G, Pavord ID, Klenerman P, Xue L. Synergistic activation of pro-inflammatory type-2 CD8(+) T lymphocytes by lipid mediators in severe eosinophilic asthma. Mucosal. Immunol. 143(2):577-590 (2019).
14. Brandsma J, Goss VM, Yang X, Bakke PS, Caruso M, Chanez P, Dahlén SE, Fowler SJ, Horvath I, Krug N, Montuschi P, Sanak M, Sandström T, Shaw DE, Chung KF, Singer F, Fleming LJ, Sousa AR, Pandis I, Bansal AT, Sterk PJ, Djukanović R, Postle AD; U-BIOPRED Study Group. Lipid phenotyping of lung epithelial lining fluid in healthy human volunteers. Metabolomics. 14(10):123. doi: 10.1007/s11306-018-1412-2 (2018)
15. Pavlidis S, Takahashi K, …. Djukanovic R, Fan Chung K; on behalf of the U-BIOPRED Study Group. “T2-high" in severe asthma related to blood eosinophil, exhaled nitric oxide and serum periostin. Eur Respir J. 53(1). doi: 10.1183/13993003.00938-2018 (2019).
16. Shrine N, Portelli MA, Djukanovic R, … Brightling CE, Wain LV, Sayers I. Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study. Lancet Respir. Med. 7(1):20-34 (2019).
17. Schofield JPR, Burg D, … Djukanović R. Stratification of asthma phenotypes by airway proteomic signatures. J Allergy Clin Immunol. 144(1):70-82 (2019).
18. Östling J, van Geest M, … Djukanović R, Vaarala O (joint senior author). IL-17-high asthma with features of a psoriasis immunophenotype. J Allergy Clin Immunol. Nov;144(5):1198-1213 (2019).
19. PHOSP-COVID Collaborative Group. Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study. Lancet Respir Med. 2022 Aug;10(8):761-775.
20. Monk PD, Marsden RJ, … Djukanovic R, Wilkinson TMA; Inhaled Interferon Beta COVID-19 Study Group. Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Respir Med. 2021 Feb;9(2):196-206.
21. Heaney LG, Busby J, Hanratty CE, Djukanovic R, …. Pavord ID; investigators for the MRC Refractory Asthma Stratification Programme. Composite type-2 biomarker strategy versus a symptom-risk-based algorithm to adjust corticosteroid dose in patients with severe asthma: a multicentre, single-blind, parallel group, randomised controlled trial. Lancet Respir Med. 2021 Jan;9(1):57-68.
Major grants:
Current (2021-2024): SHARP (Severe, Heterogeneous, Asthma Research Collaboration, Patient-Centred), €2,250,000. DRAGON (rapid and secuRe AI imaging based diagnosis, stratification, fOllow-up, and preparedness for coronavirus pandemics). Role: co-applicant. Funding: €14,342,642.
Recent: United Kingdom Refractory Asthma Stratification Programme (RASP-UK), £4,836,000. Beyond Allergic Th2 Severe Asthma (BEAT Severe Asthma), £2,680,000. Study of Mechanisms of action of Omalizumab in Severe Asthma (SoMOSA), £3,946,000.
Impact example:
Developing nebulised interferon beta as a treatment for respiratory infections in severe asthma, COPD and COVID-19.
Established large collaborative networks for severe asthma (U-BIOPRED, SHARP Clinical Research Collaboration and ICAN), placing patients at the centre of all decisions with the aim to improve understanding of disease phenotypes and endotypes and identify biomarkers predictive of clinical response to biologics.