Glucose-mediated remodeling of cardiac DNA methylation - Specifically, work in the laboratory has two primary goals: 1) to determine the role of metabolic substrate switching in the hearts of individuals with diabetes or heart failure, and 2) to define the role of cellular glucose delivery on post-translational regulation of mitochondrial enzyme activity and epigenetic regulation of gene expression that together may lead to the development of diabetic cardiomyopathy. The primary goal of the R01-funded research is to determine the role glucose fluctuations in the regulation of DNA methylation in transgenic models of glucose uptake and diabetes models. Other projects in the laboratory include determining the role of the protein post-translational modification O-GlcNAc in regulating cardiac cellular function and define the role that changes in glucose levels have on long-lasting epigenetic regulation of gene expression in a process termed “glycemic memory”. Recent studies include work defining these molecular pathways in human heart failure biopsies to determine etiology specific epigenetic signatures (as published here: https://www.nature.com/articles/s41374-018-0104-x). Finally, we have initial work looking at human samples to define racial differences in epigenetic changes that in turn impact susceptibility to diabetes and heart failure. By determining these molecular signatures of altered protein regulation and DNA structure/regulation we aim to provide critical knowledge to determining future therapeutic interventions for diabetic and heart failure patients.
Keywords - Diabetes, Hypertension, Exercise, Mitochondria, Metabolism, Glucose, Epigenetics, Gene expression, transcription, O-GlcNAc, protein modifications, DNA methylation, Histone modification, GLUT4, PDK2, PDK4
