UCD School of Biomolecular & Biomedical Science

To date, my group has focused on the investigation of cyclooxygenase expression and prostaglandin generation in vascular disease in vivo. Key aims have been to localise COX isoforms in atherosclerotic plaque and to examine the effect of COX-1 and COX-2 inhibitors on prostaglandin production in vascular disease. This has been achieved in different clinical models, which include a rat model of cerebral infarction, a rat model of intimal hyperplasia, human vascular disease and the apoE mouse model of atherosclerosis. In addition, we have generated two novel double knockout models of atherosclerosis which we use to examine the effect of COX-1 and COX-2 gene deletion on atherosclerosis development. Currently, we are using intravital microscopy to investigate platelet and leukocyte adhesion in the vascular wall of our experimental models. We are now further elucidating the mechanism(s) by which COX-1 is pro-atherogenic in this model with particular emphasis on platelet activity. Furthermore, we are investigating the effect of COX-2 on gene expression in cardiac tissue where the underlying objective is to generate a cardiac specific COX-2 transgenic model.

In addition, we have investigated if it is possible to reverse pre-established atherosclerosis. This is an important concept in the area of vascular biology as there are currently no available treatments which reverse this process. Our research has focused on PPARg agonists, in particular on dietary conjugated linoleic acid (CLA), in the regression of pre-established atherosclerosis. We have shown dietary administration of CLA reverses lesion formation in the apoE model and this has been extended to elucidate the mechanism by which CLA mediated this process in particular by focusing on target genes in the macrophage cell and investigating altered phenotype of macrophages in vitro. Furthermore, we are investigating if it is possible for a damaged blood vessel to revert to its normal physiology with CLA administration in particular by examining endothelial regeneration and platelet function in our experimental models. A major objective of the research group is to identify if there is an endogenous anti-atherosclerotic pathway which is associated with a decreased risk and/or which triggers the regression of atherosclerosis in vivo. Recently we have identified genes which provide evidence of a potential "anti-atherogenic pathway" regulated by CLA in the macrophage cell. These include genes associated with monocyte migration, monocyte to macrophage differentiation and inflammation. We are now employing a trascriptomics and proteomics in vivo to further characterise this pathway.

Prof Aldons Jake Lusis,
Dept. Human Genetics, UCLA, CA, USA

Prof Meinrad Gawaz
Eberhard Karls Universitat Tubingen, Germany

Ms. Mary Barry,
Consultant Vascular Surgeon, SVUH, Diblin

Prof. Matthew Griffin,
Professor of Transplant Medicine, NUIG, Galway 

Dr. Angela Duffy (2002) ¿ Title of Thesis: ¿Mechanisms of cyclooxygenase expression and generation of prostaglandins in vascular disease.¿

Dr. Sinead Toomey (2004) ¿ Title of Thesis:  ¿Pharmacological and Nutraceutical compounds in the treatment of atherosclerosis.¿

Dr. Sarah McClelland (2007) - Title of Thesis: ¿Modulation of Atherosclerosis: Investigation of targeted gene deletion and fatty acid intervention"