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Menick, Donald
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overview
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My laboratory is focused on the analysis of signaling and gene regulatory pathways, which play a role in cardiac failure. Recently, others and we have demonstrated that protein acetylation, regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), plays a significant role in modulating gene expression in cardiac pathologies. Importantly, treatment with HDAC inhibitors preserves ventricular remodeling and cardiac function in models of cardiac hypertrophy, myocardial infarction (MI) and heart failure. We have demonstrated that the acetylation state of specific transcription factors affects their interaction with co-activators and co-repressors. Therefore, HDACs can facilitate gene activation via the direct deacetylation of transcription factors allowing for recruitment of co-activators to the promoter. We utilize both isolated adult cardiac myocytes as well as animal models of hypertrophy, MI and heart failure to determine the signals that regulate HDACs and HATs and how the resulting changes in protein acetylation modulate cardiomyocyte and ventricular function. Our goal is to translate our basic and pre-clinical discoveries into important new therapies for patients with heart disease.
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Menick, Donald