We recently determined that hemostatic plugs formed in the microcirculation following vascular injury are composed of discrete regions with variable degrees of platelet activation.  Ongoing studies are investigating how multiple components of the platelet signaling network are integrated to produce this heterogeneous hemostatic plug architecture. To accomplish these goals, we make extensive use of multiple systems for examination of thrombosis in vitro and in vivo, including a spinning disk confocal intravital microscopy system for visualization of thrombosis in the microcirculation of mice.  Intravital microscopy approaches also involve the use of established and novel fluorescent probes for visualizing various aspects of the hemostatic response in vivo, including fluorescently labeled antibodies, fluorescent biochemical activity sensors, and genetically encoded fluorescent indicators.

Platelets express a family of cell adhesion molecules, such as ESAM and JAM-A, that are found at the tight junctions of other cell types (e.g. endothelial cells and epithelial cells).  As platelets do not form classic tight junctions the role of these proteins in platelet biology is rather unclear. They appear to be negative regulators of platelet plug formation in vivo as genetic deletion in mice leads to a mild pro-thrombotic phenotype.  Current studies are investigating the mechanisms by which this family of proteins influences platelet functions, as well as their role in platelet-leukocyte and platelet-endothelial cell crosstalk.