Gene regulation in Cardiovascular Remodelling and Inflammation

Much of our work of the group leaded by Dr. Juan Miguel Redondo centers on the regulation of calcineurin (CN) signaling in angiogenesis and inflammation. In recent years, we have characterized the mechanisms and sequences involved in the interactions of CN with NFAT and other substrates and with immunosuppressive drugs, and we have characterized how specific CN targeting modulates inflammatory responses. More recently, we have studied mediators in vascular and cardiac remodeling related to Angiotensin II and CN pathways. We are currently elucidating the mechanisms that mediate this remodeling and have generated conditional mice deficient for CN and Rcan1 isoforms in the endothelial, vascular smooth muscle, and cardiomyocyte compartments. We have already identified genes regulated by CN in different mouse models of cardiac hypertrophy (CH), and are characterizing their roles in CH using conditional cardiac CN and Rcan1mice. Another major area of interest is the mechanisms that mediate aortic diseases such as familial forms of thoracic aortic aneurysm and dissection (TAAD), including Marfan syndrome. We have identified a number of mediators that play a major role in the pathogenesis of these  diseases, and we are now characterizing the underlying mechanisms.