Research in the Vondriska Laboratory is focused on understanding the epigenomic basis of heart failure. In the basic science realm, one of the most important questions in biology is how the same genome encodes the function of the hundreds of cells in a human being. We are trying to answer this question by studying the structure and regulation of chromatin. In recent years, we have carried out the first chromatin conformation capture experiments in the heart, determining the endogenous organization of the genome in cardiac myocytes. With this blueprint, we are now answering the following questions: How do transcription neighborhoods form? What is the role of inter-chromosomal interactions and other nuclear features in genomic architecture? How do features of local accessibility relate to local and global architecture?
In the translational realm, we are examining the role of chromatin structural reorganization in heart failure. To this end, we are determining the structural features required for disease-associated gene expression and investigating how global chromatin accessibility is altered during cardiovascular disease. These studies are targeted to identify diagnostic features of the epigenome that indicate the progression or reversion of disease and to develop strategies to remodel chromatin therapeutically.