Professor, Department of Physiology and Pathophysiology
Professor, Department of Pharmacology & Therapeutics
Institute of Cardiovascular Sciences
Canada Research Chair in Molecular Cardiology in Tier I
Director, Research Development
I am interested in understanding the epigenetic regulation of cell survival and cell death signaling pathways in the heart. We have ongoing investigations directed toward understanding how epigenetic regulation of gene transcription by histone modifications influence cell survival and cell death signaling pathways by apoptosis, necrosis and autophagy respectively. We have focused our attention the NF-kB signaling pathway and regulation by the class I and class II HDACs. We have established that HDAC1/2 are recruited to the Bcl-2 protein gene promoter Bnip3 in a manner contingent upon NF-kB DNA binding. The NF-kB-HDAC complex negatively regulates Bnip3 gene transcription and suppresses cell death of cardiac myocytes under basal conditions. Interestingly, this inhibitory complex between NF-kB and HDAC1 is disrupted under hypoxic conditions concordant with the activation of p300 dependent of Bnip3 and transcription and cell death. Our work has established that HDAC modifications of p65 NF-kB serves as a molecular switch for regulating Bnip3 and cell death in cardiac cells under normal and hypoxic conditions. Ongoing studies in the laboratory are directed toward understanding the epigenetic regulation of caloric restriction and autophagy/mitophagy signaling by the sirtuins sirt-1/3 proteins on key transcription factors including FOXO and others and how these transcriptional events influence mitochondrial quality control event involving mitochondrial fission and fusion. We are interested in understanding whether mitochondrial clearance and cell death are commonly regulated by acetylation/deacetylation can be regulated during disease conditions such as myocardial infarction as a means to modulate cell death.
R3016 St Boniface Albrechtsen Research Centre