• Room 02.018 - CEM

    United Kingdom

Accepting PhD Students

PhD projects

Professor O'Kane is open to wide-ranging PhD applications from candidates with a basic science or clinical background. Her interests include respiratory failure in the critically ill, particularly the Acute Respiratory Distress Syndrome (ARDS), mechanisms if tissue damage and repair in the lung, mycobacterial infection including Tuberculosis and Non-Tuberculous Mycobacterial infection, and novel therapies including biological and cellular therapies to treat infection and inflammation in the lung. Her group works in both wet lab and clinical research, and has a particular focus on human models of the lung environment. Previous research experience is desirable although not essential.

20042020

Research output per year

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Personal profile

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

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Projects

Research Output

Corticosteroids in acute respiratory distress syndrome: a step forward, but more evidence is needed

Reddy, K., O'Kane, C. & McAuley, D., 07 Feb 2020, In : The Lancet Respiratory Medicine. 8, 3, p. 220-222 3 p.

Research output: Contribution to journalComment/debate

1 Citation (Scopus)
  • 6 Citations (Scopus)
    Open Access
    File
  • 8 Downloads (Pure)

    Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration in COVID-19 (REALIST-COVID-19): A structured summary of a study protocol for a randomised, controlled trial

    Gorman, E., Shankar-Hari, M., Hopkins, P., Tunnicliffe, W. S., Perkins, G. D., Silversides, J., McGuigan, P., Jackson, C., Boyle, R., McFerran, J., McDowell, C., Campbell, C., McFarland, M., Smythe, J., Thompson, J., Williams, B., Curley, G., Laffey, J. G., Clarke, M., O'Kane, C. & 1 others, McAuley, D. F., 03 Jun 2020, In : Trials. 21, 1, p. 462

    Research output: Contribution to journalArticle

    Open Access
    File
  • 7 Downloads (Pure)

    Subphenotypes in critical care: translation into clinical practice

    Reddy, K., Sinha, P., O'Kane, C., Gordon, A., Calfee, C. S. & McAuley, D., 01 Jun 2020, In : The Lancet Respiratory Medicine. 8, p. 631 643 p.

    Research output: Contribution to journalArticle

  • 1 Citation (Scopus)

    Prizes

    Election to Association of Physicians

    O'Kane, Cecilia (Recipient), 01 Feb 2015

    Prize: Election to learned society

    FRCPE

    O'Kane, Cecilia (Recipient), Oct 2012

    Prize: Election to learned society

  • Activities

    Clinical Academic Forum

    Aidan Cole (Organiser), , Danny McAuley (Chair), , Emma Cunningham (Organiser), , Richard Turkington (Participant), & Cecilia O'Kane (Participant)

    15 Jan 2019

    Activity: Participating in or organising an event typesParticipation in workshop, seminar, course

    UK Critical Care Research Forum

    Cecilia O'Kane (Organiser), , Murali Shyamsundar (Organiser), , Bronagh Blackwood (Organiser), & Danny McAuley (Organiser)

    07 Jun 201808 Jun 2018

    Activity: Participating in or organising an event typesParticipation in conference

    NTM symposium

    Cecilia O'Kane (Participant)

    31 Mar 2017

    Activity: Participating in or organising an event typesParticipation in conference

    Nicotine & Tobacco Research (Journal)

    Cecilia O'Kane (Peer reviewer)

    2017 → …

    Activity: Publication peer-review and editorial work typesPublication peer-review

    How to combine research and clinical work?

    Cecilia O'Kane (Invited speaker)

    19 Oct 2017

    Activity: Talk or presentation typesInvited talk

    Thesis

    Human Mesenchymal Stromal Cell Regulation of Pulmonary Macrophage Populations in the Acute Respiratory Distress Syndrome

    Author: Morrison, T., 2017

    Supervisor: Krasnodembskaya, A. (Supervisor), Kissenpfennig, A. (Supervisor) & O'Kane, C. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy

    File

    Investigation of the host-mediated proteolytic response to pulmonary Mycobacterium Avium Complex infection

    Author: McFetridge, S., Jul 2020

    Supervisor: O'Kane, C. (Supervisor), McMullan, R. (Supervisor) & Schroeder, G. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy