Projects per year
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
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
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Collaborations and top research areas from the last five years
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R1141CEM: The Role of Extracellular Proteasome in the acutely inflamed lung
Taggart, C., McAuley, D., O'Kane, C. & Weldon, S.
02/01/2020 → …
Project: Research
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R6609CEM: Dissecting the molecular pathogenesis of Legionella spp. in human lung models
16/04/2019 → …
Project: Research
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Effect of total cholesterol and statin therapy on mortality in ARDS patients: a secondary analysis of the SAILS and HARP-2 trials
Pienkos, S. M., Moore, A. R., Guan, J., Levitt, J. E., Matthay, M. A., Baron, R. M., Conlon, J., McAuley, D. F., O’Kane, C. M. & Rogers, A. J., 28 Mar 2023, (Early online date) In: Critical Care. 27, 1, 126.Research output: Contribution to journal › Article › peer-review
Open AccessFile6 Downloads (Pure) -
Repair of acute respiratory distress syndrome in COVID-19 by stromal cells (REALIST-COVID Trial): A multicentre, randomised, controlled trial
Gorman, E. A., Rynne, J., Gardiner, H. J., Rostron, A. J., Bannard-Smith, J., Bentley, A. M., Brealey, D., Campbell, C., Curley, G., Clarke, M., Dushianthan, A., Hopkins, P., Jackson, C., Kefela, K., Krasnodembskaya, A., Laffey, J. G., McDowell, C., McFarland, M., McFerran, J., McGuigan, P., & 12 others , 08 May 2023, (Early online date) In: American Journal of Respiratory and Critical Care Medicine.Research output: Contribution to journal › Article › peer-review
Open Access -
Understanding the role of mesenchymal stromal cells in treating Covid-19 acute respiratory distress syndrome
O'Kane, C. M. & Matthay, M. A., Feb 2023, In: American Journal of Respiratory and Critical Care Medicine. 207, 3, p. 231-233Research output: Contribution to journal › Editorial › peer-review
Open AccessFile25 Downloads (Pure) -
Acute respiratory distress syndrome in adults: diagnosis, outcomes, long-term sequelae, and management
Gorman, E. A., O'Kane, C. M. & McAuley, D. F., 01 Oct 2022, In: Lancet (London, England). 400, 10358, p. 1157-1170Research output: Contribution to journal › Article › peer-review
Open AccessFile628 Downloads (Pure) -
Airwaves
Griffiths, M., O'Kane, C. M. & Quint, J. K., Sep 2022, In: Thorax. 77, 9, 1 p., 845.Research output: Contribution to journal › Article
Prizes
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Election to Association of Physicians
O'Kane, Cecilia (Recipient), 01 Feb 2015
Prize: Election to learned society
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Activities
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UK Critical Care Research Forum
Cecilia O'Kane (Organiser), Murali Shyamsundar (Organiser), Bronagh Blackwood (Organiser) & Danny McAuley (Organiser)
07 Jun 2018 → 08 Jun 2018Activity: Participating in or organising an event types › Participation in conference
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Aspirin inhibits neutrophilic inflammation in human models of acute lung injury
Cecilia O'Kane (Invited speaker)
07 Dec 2017Activity: Talk or presentation types › Invited talk
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How to combine research and clinical work?
Cecilia O'Kane (Invited speaker)
19 Oct 2017Activity: Talk or presentation types › Invited talk
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NTM symposium
Cecilia O'Kane (Participant)
31 Mar 2017Activity: Participating in or organising an event types › Participation in conference
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Nicotine & Tobacco Research (Journal)
Cecilia O'Kane (Peer reviewer)
2017 → …Activity: Publication peer-review and editorial work types › Publication peer-review