Our team entitled “Signaling and pathophysiology of heart failure” associates clinicians and researchers sharing a common scientific background and interest in understanding the molecular and cellular mechanisms involved in Heart Failure (HF). The final objective is to identify relevant targets to prevent or reverse HF.

We have identified new signaling pathways involved in cardiac hypertrophy and failure. These signaling events involve the cAMP-binding proteins Epac and Carabin that couple membrane receptors to pathological cardiac remodeling. It also involves the metabolism of catecholamines by monoamine oxidase-A (MAO-A) as a source of reactive oxygen species (ROS) in HF and cardiac aging.

Our goal now is to dissect the signaling pathways of Epac/Carabin/MAO-A in order to understand how these proteins influence cell fate. We will analyze their target genes and epigenetic mark during cardiac remodeling. Our efforts also aim at better understanding the importance of MAO-A/ROS axis in the development of HF associated with aging.

Our approach is multidisciplinary: we are seeking pharmacological modulators of these therapeutic targets (in silico screening and HTS) and develop mouse lines and gene therapy vectors to identify their role in the myocardium. Our methodologies combine cell culture, cell imaging, biochemical assays, mass spectrometry, molecular biology (RNA Seq, ChIP-Seq, ..) and experimental models of heart failure.