Staff Profile




General Profile Information
Staff Name Dr Cecilia O'Kane
Job Title Clinical Senior Lecturer
Location H.S.B Block 10 MBC Site
Room Number 0G.002A
School School of Medicine, Dentistry and Biomedical Sciences
Contact Details
Telephone +44 (0)28 9097 5876
E-mail c.okane@qub.ac.uk
Teaching
Currrently teach on the CF SSC for Medicine: involved in the module design, lecturing and assessment



Research Statement

My areas of research focus largely on the processes that mediate inflammation and repair in inflammatory lung disease. I am particualrly interested in the role of the matrix metalloproteinases (MMPs) in both initiating and perpetuating the process of tissue damage, but also mediating a reparative process allowing recovery. Broad spectrum MMP inhibition has been an unsuccessful therapeutic strategy in a number of inflammatory diseases. We aim to profile the expression of these proteases at different stages of disease and identify which initiate the damage and which regulate the repair process at the given time points. Ultimately the aim of this work is to allow targetted MMP inhibition at specific stages of disease, initially to reduce inflammation, and at later time points to promote normal epithelial repair and inhibit fibrosis.

My clinical specialties are tuberculosis and cystic fibrosis. Both are characterised by chronic infection leading to inflammation and extensive tissue damage. High protease activity has been well-described in tuberculosis, and along with Cliff Taggart and Danny McAuley I am investigating the capacity of anti-proteases to modulate inflammatory damage but also mycobacterial survival. In Cystic Fibrosis we have established models of direct infection of the lung parenchymal and inflammatory cells with typical CF pathogens (in particular Pseudomonas aerugionsa) and are investigating the regulation and effects of MMP secretion in response. We have a further clinical study about to begin examining in vivo exprssion of these proteases and investigating the mechanism that induce airway remodelling or destruction in this disease.

Along with Danny McAuley I work on proteases and inflammatory mediators in acute lung injury (ALI). We have established in vitro models and a human in vivo model of acute lung inflammation and have used these to test potential novel therapuetics in ALI that target inflammation and MMP production (including statins and Keratinocyte Growth Factor), and have progressed these to early clinical trial stage. We have further projects looking at the role of RAGE and Oncostatin M in mediating inflammatory lung disease, and are also investigating the capacity of endogenously produced anti-protease molecules to modulate these responses (particularly SLPI and elafin) in collaboration with Cliff Taggart. We have further collaborations with Birmingham, Edinburgh, UCL, Galway and San Francisco in ALI.  

Finally I have an interest in the process of aberrant tissue remodelling that leads to cutaneous fibrosis. Many of the processes that regulate fibrosis in the lungs are common to other organs. I am currently supervising a clinical fellow  investigating the mechanisms of skin fibrosis in scleroderma.

 





Membership Of Other Societies / Professional Activities


 External Research Collaborations

 

Prof John Simpson (Newcastle University)

MMP activity as a biomarker of ventilator associated pneumonia

 

Prof Andrew Fisher (Newcastle University)

MMPs in the reconditioned human lung 

 

Prof John Laffey (Galway University Hospitals)

Matrix metalloproteinases (MMPs) in ventilator associated lung injury

 

Dr David Thickett (University of Brimingham and University of Warwick)

Epithelial to mesenchymal transition as a mechanism of fibrosis in ALI

Vit D deficiency and outcomes in treatment of tuberculosis

 

Prof Michael Matthay (University of California, San Francisco)

Protective role of KGF and anti-microbial peptides in LPS induced acute lung injury

 

Dr Mark Griffiths (Imperial College London)

Iron-binding molecules and ALI 

 

Prof Chris Denton (University College London)

Role of epithelial to mesenchymal transition in mediating cutaneous fibrosis in scleroderma

 

Prof Danny Altmann (Imperial College London)

Serological immune responses to Burkholderia species in CF patients

 

Invited talks

Invited seminar speaker to VA Medical Centre San Francisco June 2009

 

Review process

Review papers for Thorax, European Respiratory Journal, Critical Care Medicine, American Journal of Physiology: Lung Cellular and Molecular Physiology, Journal of Immunology and Archives of Biochemistry and Biophysics.

Expert reviewer for MRC and National Institute for Health Research (NIHR)

Peer review grants for MRC, British Lung Foundation, local Trust and West Midlands Charitable Funds

 

Contribution to national meetings

Chaired scientific sessions at the annual BTS winter meeting 2009 and 2010 

Organisation/chairing of UKALI meetings bi-annually





Awards And Honours/major Prizes
Winner of British Thoracic Society Young Investigator Award, 2005 



Publications
Chapter(s)
TitleBook TitleYear
Potential Mechanisms by which statins modulate the development of Acute Lung Injury Yearbook of Intensive Care and Emergency Medicine 2007
Matrix metalloproteinases: a potential role in the pathogensis of ARDS Yearbook of Intensive Care and Emergency Medicine 2004
Journal(s)
TitleJournal NameYear
Benefits of statins in the critically ill: promising but not proven. Critical Care Medicine Vol 39(6) (1599-1600)  DOI 2011
Matrix Metalloproteinases in Acute Lung Injury: mediators of injury and drivers of repair. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology Vol epub ahead of print (1599-1600)  DOI 2011
Evolution of the inflammatory and fibroproliferative responses during resolution and repair following ventilator induced lung injury in the rat Anesthesiology Vol in press (in press-in press)  2011
Novel pulmonary biomarkers in the diagnosis of VAP. Thorax Vol 65(3) (190-192)  DOI 2010
A potential role for keratinocyte growth factor and clarithromycin in the treatment of paraquat overdose. QJM : monthly journal of the Association of Physicians Vol epub ahead of print (1-1)  DOI 2010
STAT3, p38 MAP Kinase and NF-{kappa}B Drive Unopposed Monocyte-dependent Fibroblast MMP-1 Secretion in Tuberculosis. American Journal of Respiratory Cell and Molecular Biology Vol 43(4) (465-474)  DOI   2010
A stepwise approach to justify phase III randomized clinical trials and enhance the likelihood of a positive result. Critical Care Medicine Vol 38(10 Suppl) (S523-7-474)  DOI 2010
High MMP-9 activity characterizes pleural tuberculosis correlating with granuloma formation European Respiratory Journal Vol 33(1) (134-141)  DOI   2009
Salbutamol up-regulates matrix metalloproteinase-9 in the alveolar space in the acute respiratory distress syndrome. Critical Care Medicine Vol 37(7) (2242-2249)  DOI 2009
Keratinocyte growth factor in acute lung injury--a work in progress. Critical Care Medicine Vol 37(5) (1813-1814)  DOI 2009
Comment on Intensive Care Medicine Vol 35 (1494-1495)  DOI 2009
Monocyte-dependent oncostatin M and TNFa synergize to stimulate unopposed matrix metalloproteinase-1/3 secretion from human lung fibroblasts in tuberculosis European Journal of Immunology Vol 38(5) (1321-1330)  DOI   2008
Does MMP-12 play a role in human lung fibrosis? American Journal of Respiratory Cell and Molecular Biology Vol 38(2) (247-247)  2008
Synergistic up-regulation of epithelial cell matrix metalloproteinase-9 secretion in tuberculosis. American Journal of Respiratory Cell and Molecular Biology Vol 37(4) (431-437)  2007
Monocyte-dependent fibroblast CXCL8 secretion occurs in tuberculosis and limits survival of mycobacteria within macrophages Journal of Immunology Vol 178(6) (3767-3776)  2007
Mycobacterium tuberculosis up-regulates matrix metalloproteinase-1 secretion from human airway epithelial cells via a p38 MAPK switch Journal of Immunology Vol 175(8) (5333-5340)  2005
Mycobacterium tuberculosis but not vaccine strain specifically up-regulates matrix metalloproteinase-1 American Journal of Respiratory and Critical Care Medicine Vol 172(12) (1596-1604)  2005
The paradox of matrix metalloproteinases in infectious disease Clinical and Experimental Immunology Vol 142(1) (12-20)  2005
Transcriptional mechanisms regulating alveolar epithelial cell-specific CCL5 secretion in pulmonary tuberculosis Journal of Biological Chemistry Vol 279(26) (27199-27210)  2004