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    United Kingdom

Accepting PhD Students

20042019
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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

Fingerprint Dive into the research topics where Cecilia O'Kane is active. These topic labels come from the works of this person. Together they form a unique fingerprint.

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Adult Respiratory Distress Syndrome Medicine & Life Sciences
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Network Recent external collaboration on country level. Dive into details by clicking on the dots.

Projects 2010 2019

Research Output 2004 2019

Development and Validation of Parsimonious Algorithms to Classify ARDS Phenotypes: Secondary Analyses of Randomised Controlled Trials

Sinha, P., Delucchi, K. L., McAuley, D., O'Kane, C., Matthay, M. & Calfee, C. S., 01 Aug 2019, (Accepted) In : The Lancet Respiratory Medicine.

Research output: Contribution to journalArticle

Randomized Controlled Trials
Phenotype
Logistic Models
Bicarbonates
Protein C
2 Citations (Scopus)
Open Access
File
Acidosis
Stem cells
Mesenchymal Stromal Cells
Repair
Lung
4 Citations (Scopus)

IL4Rα Signaling Abrogates Hypoxic Neutrophil Survival and Limits Acute Lung Injury Responses In Vivo

Harris, A. J., Mirchandani, A. S., Lynch, R. W., Delaney, L., Small, D., Coelho, P., Watts, E. R., Sadiku, P., Griffith, D., Dickinson, R. S., Clark, E., Willson, J. A., Morrison, T., Mazzone, M., Carmeliet, P., Ghesquiere, B., O'Kane, C., McAuley, D., Jenkins, S. J., Whyte, M. K. B. & 1 othersWalmsley, S. R., 08 Mar 2019, In : American Journal of Respiratory and Critical Care Medicine.

Research output: Contribution to journalArticle

Acute Lung Injury
Neutrophils
Interleukin-4
Adult Respiratory Distress Syndrome
Interleukin-13

Randomised controlled trial and process evaluation of biomarker-guided antibiotic stewardship in suspected ventilator-associated pneumonia

Hellyer, T. P., McAuley, D., Walsh, T. S., Anderson, N. H., Conway Morris, A., Singh, S., Dark, P., Roy, A. I., Perkins, G. D., McMullan, R., Emerson, L., Blackwood, B., Wright, S. E., Kefala, K., O'Kane, C., Baudouin, S. V., Paterson, R. W., Rostron, A. J., Agus, A., Bannard-Smith, J. & 19 othersRobin, N., Welters, I., Bassford, C., Yates, B., Spencer, C., Laha, S., Hulme, J., Bonner, S., Linnett, V. C., Sonksen, J., van den Broeck, T., Boschman, G., Keenan, J., Scott, J., Allen, A. J., Phair, G., Parker, J., Bowett, S. A. & Simpson, A. J., 01 Aug 2019, (Accepted) In : The Lancet Respiratory Medicine.

Research output: Contribution to journalArticle

Prizes

Election to Association of Physicians

Cecilia O'Kane (Recipient), 01 Feb 2015

Prize: Election to learned society

FRCPE

Cecilia O'Kane (Recipient), Oct 2012

Prize: Election to learned society

Edinburgh
Physicians
Elections

Activities 2008 2018

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

Aspirin inhibits neutrophilic inflammation in human models of acute lung injury

Cecilia O'Kane (Invited speaker)
07 Dec 2017

Activity: Talk or presentation typesInvited talk

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

NTM symposium

Cecilia O'Kane (Participant)
31 Mar 2017

Activity: Participating in or organising an event typesParticipation in conference

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

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