Izhak Kehat, MD PhD
Assistant Professor of Cardiology
MD, 1997 - Technion, Israel
PhD, 2005 - Technion, Israel
Investigating the epigenetics of cardiac hypertrophy and heart failure
Heart failure is caused by various disorders that reduce the efficiency of the heart muscle by damage or work overload. Work overload provokes the heart to enlarge through hypertrophic growth of cardiomyocytes (heart cells), resulting in further deterioration and eventually death. Our goal is to identify the epigenetic molecular mechanisms responsible for cardiac hypertrophy during heart failure and to translate what we learn into state-of-the-art therapies that could eventually reduce deaths due to heart disease. We focus mainly on genome organization and epigenetic modifications, trying to understand the global mechanisms that control gene expression in the heart. We employ advanced genetic approaches to map the organization of the genome in heart cells and understand how epigenetics, genome organization, signalling, and changes in gene expression result in heart cell growth and heart failure. For more information, see my Lab webpage: http://kehatlab.net.technion.ac.il/
Abend A and Kehat I. 2015. Histone deacetylases as therapeutic targets--from cancer to cardiac disease. Pharmacol Ther. 147, 55-62.
Kehat I. 2012. Novel strategies for the treatment of heart failure. Rambam Maimonides Med J. 3(2), e0011.
Kehat I, Accornero F, Aronow BJ, and Molkentin JD. 2011. Modulation of chromatin position and gene expression by HDAC4 through interaction with nucleoporins. J Cell Biol. 193, 21-9.
Kehat I, Davis J, Tiburcy M, Accornero F, Saba-El-Leil MK, Maillet M, York AJ, Lorenz JN, Zimmermann WH, Meloche S, and Molkentin JD. 2011. Extracellular Signal-Regulated Kinases 1 and 2 Regulate the Balance Between Eccentric and Concentric Cardiac Growth. Circ Res. 108, 176-83.
Kehat I and Molkentin JD. Molecular pathways underlying cardiac remodeling during pathophysiologic stimulation. 2010. Circulation. 122, 2727-35.
Different types of work overload induce different types of growth patterns of the heart and the heart cells.
Pressure overload results in increased heart cell width, while volume overload results in increased heart cell length (as illustrated in the centre). We are using advanced genetic approaches to map the genome organization and gene expression changes that control these events. In the figure a circular map of chromosome 5 is shown with a heat map of gene expression in the heart. Genes that are upregulated in hypertrophy are highlighted by red triangles. We are exploring the spatial and functional interactions of these genomic loci.