Professor, Department of Physiology & Pathophysiology
Principal Investigator, Institute of Cardiovascular Sciences
A major project in our laboratory is the study of the transcriptional regulation of cardiac extracellular matrix production by the transcription factor scleraxis. Our results have shown the scleraxis is both sufficient and required for matrix synthesis, and suggest that scleraxis may play a causative role in cardiac fibrosis, in which excessive matrix is made. Our preliminary data indicates that the HDAC inhibitor TSA, which has been shown to ameliorate cardiac fibrosis in a number of animal models, reduces scleraxis gene expression, thus providing a potential mechanism to explain the salutary effects of TSA on fibrosis. We are also completing a study of factors that regulate the expression of PGC-1a, which governs mitochondrial biogenesis in cardiomyocytes. Our published work demonstrated that PGC-1a expression is governed by HDACs such as HDAC5, and that hypoxia reduces PGC-1a expression by increasing histone deacetylation of the PGC-1a promoter. Our current preliminary further indicates that this process is dependent upon the recruitment of NFkB to the PGC-1a promoter during hypoxia.
R4008 St Boniface Hospital Research Center