The role of c-myc in cardiac hypertrophy and heart failure. (360G-Wellcome-086797_Z_08_A)

The aim of this project is to clarify the role of c-myc in heart failure by achieving the following objectives; 1. Detailed examination of the expression of c-myc human heart failure 2. ChiP-seq analysis of c-myc bound DNA loci in control and end stage dilated human cardiomyopathic hearts 3. Examination of c-myc expression in animal models of fibrosis and . heart failure in association with analysis of angiogenesis, apoptosis, extra-cellular matrix remodelling and DNA damage 4. Assessment of DNA damage, protection or susceptibility to fibrosis and dilatation in a cmyc expression and induction in a myocyte specific inducible transgenic c-myc overexpressing mouse model The expected beneficial outcomes of this project are i) clarity on the expression and level at which expression of c-myc is regulated through the dynamic process of heart failure, ii) identification of genomic localization of c-myc and the mechanisms by which c-myc regulates cardiac gene expression and iii) the role of c-myc in the regulation or deregulation of features of heart failure including DNA damage and fibrosis. These outcomes will allow for future work to examine how mechanisms in c-myc-related pathways may be targeted for novel heart failure therapy, and to improve the basic understanding of molecular biology of both heart failure and c-myc-DNA interactions.