The calcium-calcineurin-NFAT (CN-NFAT) pathway regulates development of the immune, vascular and nervous systems, heart valve morphogenesis, and pancreatic beta-cell function, and is implicated in many related pathological processes. We study the regulation and function of CN-NFAT signaling in lymphocyte activation, angiogenesis and cardiac hypertrophy. Much of our work relates to molecular interactions of the phosphatase calcineurin with NFAT transcription factors and other substrates and regulators. This work has identified sequence motifs important for these interactions and sheds light on the mechanism of immunosuppressive drugs.

Our work on angiogenesis addresses the regulation of NFAT in endothelial cells by VEGF and the profile and actions of prostanoids released by activated endothelium. We use retinopathy of prematurity (ROP) as a model of the mechanisms of neovessel formation in ischemic retinopathies, and are using lentiviral vectors to identify potential therapeutic targets. We are also analyzing the gene expression program triggered by angiotensin II (Ang-II) in cardiomyocytes and vascular smooth muscle and the role of CN-NFAT signaling in these processes. Likewise we are dissecting signaling pathways involved in abdominal aortic aneurysim (AAA) triggered by infusion of Ang-II in ApoE-/- mice.

A separate area of interest, directed by Dr. E. Cano, relates to the inflammatory reaction initiated by stroke. Cerebral ischemia triggers local production of inflammatory mediators, of which glial cells are an efficient source. This production sustains immune-inflammatory signaling if not halted by endogenous or exogenous anti-inflammatory agents. We are interested in the signaling pathways that contribute to lesion expansion, or conversely have a role in lesion containment and repair of the injured brain. In this context, we have been studying the role of calciumdependent pathways in astroglial cells.