Donald R. Menick, Ph.D., is associate director of the Medical Scientist Training Program and professor in the Division of Cardiology within the Department of Medicine at the MUSC College of Medicine. His laboratory investigates the signaling and gene-regulatory pathways involved in heart failure. His research team has demonstrated that protein acetylation, regulated by histone acetyltransferases and histone deacetylases, plays a significant role in modulating gene expression in cardiac pathologies.
Treatment with histone deacetylase inhibitors has been shown to preserve ventricular remodeling and cardiac function in preclinical models of cardiac hypertrophy, myocardial infarction, ischemia-reperfusion injury and heart failure. Dr. Menick’s research has also determined that these inhibitors promote the polarization of inflammatory M1 macrophages into anti-inflammatory M2 macrophages, reducing harmful cardiac remodeling and preserving cardiac function following myocardial infarction.
This research provided the first evidence that the benefits of histone deacetylase inhibition result, in part, from its ability to alter macrophage polarization, a cellular mechanism that was historically underrecognized in cardiac pathologies. Dr. Menick’s work has also identified a mechanism that serves as a model for understanding how histone deacetylases can mediate both the repression and activation of gene expression.
His laboratory has identified an important mechanism through which histone deacetylase inhibitors can repress cardiac gene expression by altering the acetylation state of transcriptional co-activators and co-repressors. The research team has also shown that the acetylation state of specific transcription factors affects their interactions with co-activators and co-repressors. Histone deacetylases may therefore facilitate gene activation through the direct deacetylation of transcription factors, allowing co-activators to be recruited to the promoter.
The overarching goal of Dr. Menick’s research is to translate basic and preclinical discoveries into new therapies for patients with heart disease.