Our laboratory is interested in understanding mechanisms of inflammation focusing both on the molecular basis of neutrophil recruitment, activation and function in autoimmune mediated diseases, and the endothelial dependent pathways regulating vascular permeability to macromolecules. In addition to our interest in leukocyte biology, our research has a strong vascular biology focus. Vascular permeability permits the passage of small molecules required for maintaining tissue fluid homeostasis. An increase in permeability is a hallmark of inflammation, and hyperpermeability and loss of endothelial barrier function is associated with many diseases from acute respiratory distress syndrome to diabetes and cancer. We study mechanisms of cAMP dependent regulation of endothelial cell junction remodeling, a dynamic process that controls vascular integrity, permeability and cell migration. We aim to determine how cAMP induced activation of Epac1, a cAMP responsive guanine exchange factor for Rap GTPases markedly increases basal endothelial barrier function and counteracts leakage induced by permeability inducing agents. In particular, we focus on delineating the role of Epac1, Rap GTPases, A-kinase anchoring protein-9 (AKAP9) and microtubule dynamics in this process.