Supervisor View Full Details

• physiology and non-communicable disease
• bioengineering/medical devices

• Medicine
• Surgery
• Anaesthetics
• Pathology

• Cardiology
• Cardiac Surgery
• Physiology
• Respiratory Medicine
• Vascular Medicine
• Other

Pathology

Our research investigates the pathogenesis of acute and chronic, non-communicable lung diseases such as COPD, idiopathic pulmonary fibrosis, pulmonary hypertension and ARDS (see sample publications below). We focus on translational research to examine the relevance of basic research discoveries to clinical diseases, using clinical samples and data. We aim to identify new biomarkers and targets that can lead to innovative therapeutic interventions.
Funding: Science Foundation Ireland, Health Research Board and UCD Foundation

Sample recent publications.
Rowan et al. (2016). Hypoxic pulmonary hypertension in chronic lung diseases: novel vasoconstrictor pathways. Lancet Respir Med, 4(3), 225-236.
Murphy et al. (2016). Altered Expression of Bone Morphogenetic Protein Accessory Proteins in Murine and Human Pulmonary Fibrosis. Am J Pathol, 186(3), 600-615.
McCullagh et al. (2015). Elevated plasma CXCL12alpha is associated with a poorer prognosis in pulmonary arterial hypertension. PLoS One, 10(4), e0123709.
Ryan et al. (2014). Pulmonary vascular dysfunction in ARDS. Ann Intensive Care, 4, 28. doi:10.1186/s13613-014-0028-6 s13613-014-0028-6
Adamali et al. (2012). Macrophage migration inhibitory factor enzymatic activity, lung inflammation, and cystic fibrosis. American journal of respiratory and critical care medicine, 186(2), 162-169.
Cahill et al. (2012). Gremlin plays a key role in the pathogenesis of pulmonary hypertension. Circulation, 125(7), 920-930.

Project 1. Mechanisms of remodeling and fibrosis in chronic lung disease.
We have shown that Gremlin1, an endogenously produced antagonist of bone morphogenetic proteins, is selectively increased in hypoxic lungs, and is an important signalling molecule in the development of pulmonary hypertension (Cahill et al 2012, see references above). More recently we have found that several other related bone morphogenetic protein antagonists are altered in hypoxic and fibrotic lung diseases (Murphy et al 2015 and unpublished data) suggesting that these also contribute to fibrosis and remodeling. This project will examine the role of these antagonists in other chronic lung diseases using clinical samples, and determine their relationship to disease severity and progression. The underlying molecular mechanisms will be elucidated in complimentary work using cell culture and murine models. This work will be undertaken in collaboration with Professor Michael Keane (Professor of Medicine St Vincent?s University Hospital) and Dr Aurelie Fabre (Consultant Pathologist, St Vincent?s University Hospital).

Project 2.
Title: Increasing donor lung supply for transplantation using novel ex vivo lung perfusion mechanisms.
Ex vivo lung perfusion (EVLP) has become an important technique to recondition and preserve donor lungs for lung transplantation. Recently, we have discovered a novel physiological phenomenon in the regulation of pulmonary endothelial function that has led to the development of a new artificial perfusate that significantly extends the period for which lungs can be maintained during EVLP and has the potential to improve the supply of donor lungs (patent submitted). This project will elucidate the mechanisms by which this solution protects against pulmonary vascular leak and oedema and extend testing to use in human lungs. It will be undertaken in collaboration with Ms Karen Redmond (Consultant Cardiothoracic Transplant Surgeon, Mater Misericordiae University Hospital) and Dr Aurelie Fabre (Consultant Pathologist).