Cecilia O'Kane
    View graph of relations

    Research Statement

    My research focuses understanding the pathophysiological mechanisms driving alveolar inflammation and injury in ARDS (acute respiratory distress syndrome), a devastating illness causing respiratory failure in the critically ill, and exploring new therapeutic interventions in clinically relevant human models, through to clinical trials.
    My group’s model systems include in vitro primary human cell work, ex vivo lung tissue slice culture, ex vivo whole lung perfusion (EVLP) models and modelling alveolar inflammation in healthy volunteers by LPS inhalation. These model systems provide proof of concept of mechanisms driving inflammation, injury and repair in human lung tissue and support the progression to clinical trials. Data from these model systems have led to clinical trials of statins, KGF and aspirin in patients with ARDS.
    Recently we have been expanding the EVLP model system from LPS injury to include mechanical and bacterial injuries, to increase clinical relevance.
    Current major projects include:
    - the REALIST trial, a Wellcome Trust HICF-funded trial of umbilical cord-derived mesenchymal stromal cells in patients with moderate-severe ARDS, aiming to begin recruitment to the phase 1 study in autumn 2018. This study will test the safety and efficacy of novel MSCs in reducing inflammation and promoting repair in ARDS. A detailed mechanistic study will run alongside the clinical trial, allowing us to gain invaluable insight into mechanisms of action of MSCs in critically ill patients. This study involves collaboration with Prof Michael Matthay (UCSF), Prof John Laffey (NUIG), NHSBT UK, and an industrial partner (Orbsen).
    - stratification studies in ARDS. Our biobanks of clinical samples from our patients with ARDS are an important resource allowing us not only to understand mechanisms of efficacy of an intervention in clinical trials but also allowing the characterisation of patient subgroups within ARDS. A secondary analysis of the HARP-2 study showed that patients who both were inotrope dependent and had higher systemic markers of inflammation (as evidenced by high sTNFR1 plus IL-6) at time of recruitment to the clinical trial, had reduced mortality when treated with simvastatin than those treated with placebo. This work in collaboration with Carolyn Calfee, a clinician scientist, and Kevin Delucchi, a biostatistician, at UCSF, has led to an important new programme trying to develop a point of care assay to allow stratification of patients into hyperinflammatory or non-hyperinflammatory phenotypes, which may have different treatment responses to clinical trial interventions. A recent successful Innovate UK application with Randox Laboratories will pilot the development of this assay and validate its use to stratify patients at time of recruitment.

    Additional external collaborations include diagnostic biomarkers for ventilator associated pneumonia (John Simpson, Newcastle), proteases in ARDS (David Thickett, Birmingham), PCLS -precision cut lung slices – and EVLP to model ARDS (Mark Griffiths, London).

    Clinically I work in the field of mycobacterial lung infection. The non-tuberculous mycobacteria (NTM) are an increasingly common clinical problem, driving lung tissue destruction and debility. Antibiotic regimens are highly unsatisfactory, with both poor tolerability and poor bacterial clearance. Mechanisms of virulence and host response differ from TB, but are poorly understood. My group is currently establishing models of infection, along with Dr Gunnar Schroeder, Dr anna Krasnodembskaya and Dr Beckie Ingram to investigate these, and test new antimicrobial strategies.

    Teaching

    Currrently teach on the CF SSC for Medicine: involved in the module design, lecturing and assessment

    Frequent Journals

    • Thorax

      ISSNs: 0040-6376, 1468-3296

      BMJ Publishing Group

      Scopus rating (2017): CiteScore 4.1 SJR 3.381 SNIP 2.215

      Journal

    • American Journal of Respiratory and Critical Care Medicine

      ISSNs: 1073-449X

      Additional searchable ISSN (Electronic): 1535-4970

      American Thoracic Society

      Scopus rating (2017): CiteScore 5.1 SJR 5.942 SNIP 2.998

      Journal

    • European Respiratory Journal

      ISSNs: 0903-1936

      Additional searchable ISSN (Electronic): 1399-3003

      EUROPEAN RESPIRATORY SOC JOURNALS LTD

      Scopus rating (2017): CiteScore 5.16 SJR 3.788 SNIP 2.396

      Journal

    • Critical Care Medicine

      ISSNs: 0090-3493

      Lippincott Williams and Wilkins

      Scopus rating (2017): CiteScore 3.24 SJR 3.116 SNIP 2.161

      Journal

    • Trials

      ISSNs: 1745-6215

      BioMed Central

      Scopus rating (2017): CiteScore 2.17 SJR 1.291 SNIP 0.819

      Journal

    View all »

    Contribution to conference papers, events and activities

    ID: 48772