My research is primarily focused on investigations of tissue remodelling that occur during the development and progression of diseases, such as, hypertension, heart failure and viral infections (Hepatitis C and HIV). The purpose is to better understanding how regulation of matrix metalloproteinases contribute to these diseases and to identify the various modulatory mechanisms that influence outcome through signalling crosstalk.
In our cardiovascular programme, we have established some understanding of remodelling consequences following exposure of b–agonists, by identifying a unique mechanistic pathway responsible for altering MMP activity. This has important implications for the development of new pharmacological targets, as we continue to uncover the involvement of novel proteins linked to the pathogenesis of cardiovascular disease. In a complementary program of investigations, where we have identified decreases in matrix metalloproteinase activity in Hepatitis C-infected patients following treatment with pegylated interferon and ribavirin. Interestingly, this effect appears to be mediated by immune cells rather than cell types directly associated with liver fibrosis. Findings from this line of enquiry have important implications towards understanding “off-target” adverse effects experienced by patients receiving HIV and Hepatitis C therapy. Knowledge of these molecular factors and their involvement in the normal physiology and pathophysiology of disease will impact on the rational design of improved therapeutic strategies. By using an integrated translational approach, it is envisaged that these studies will pinpoint mechanisms contributing to tissue remodelling, and provide a basis for novel therapeutic strategies to limit adverse tissue remodelling.
Matrix metalloproteinase activity in a cross section of aorta
For further information about Professor Paul Spiers please view his CV Profile
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