Caused by mutations in the FBN1 gene (fibrillin-1), Marfan Syndrome (MFS) is multi-system disorder also affecting the cardiovascular system. Recent data suggest that cardiomyopathy may be a primary manifestation. In this proposal, we aim to analyze human models of MFS by coupling human induced pluripotent stem cells (hiPSC), with CRISPR gene editing, differentiation, detailed cardiomyocyte phenotyping and mechanistic interrogation.