Platelet granule exocytosis – As recently as the late 1990s, the mechanisms by which platelets release their granule contents was a black box. It was understood that platelet agonists stimulate release of bioactive compounds and proteins, and that this ‘platelet release reaction’ was important in the pathophysiology of myocardial infarction and stroke. Yet the machinery responsible for membrane fusion events required for granule exocytosis had not been described. The Flaumenhaft laboratory was the first to demonstrate a functional role for SNARE proteins in platelet granule exocytosis. We and other laboratories subsequently identified the SNARE isoforms required for platelet secretion. We described the signaling cascades that mediate granule secretion and determined how the exocytotic machinery interacts with the cytoskeleton in order coordinate cargo release with the dramatic morphological transformation that occurs during platelet activation. We have worked with mice deficient in specific SNARE isoforms to dissect the role of platelet granule release in thrombus formation, demonstrating roles for VAMP-8 and VAMP-7 in platelet function during thrombus formation.

Platelet granule exocytosis – As recently as the late 1990s, the mechanisms by which platelets release their granule contents was a black box. It was understood that platelet agonists stimulate release of bioactive compounds and proteins, and that this ‘platelet release reaction’ was important in the pathophysiology of myocardial infarction and stroke. Yet the machinery responsible for membrane fusion events required for granule exocytosis had not been described. The Flaumenhaft laboratory was the first to demonstrate a functional role for SNARE proteins in platelet granule exocytosis. We and other laboratories subsequently identified the SNARE isoforms required for platelet secretion. We described the signaling cascades that mediate granule secretion and determined how the exocytotic machinery interacts with the cytoskeleton in order coordinate cargo release with the dramatic morphological transformation that occurs during platelet activation. We have worked with mice deficient in specific SNARE isoforms to dissect the role of platelet granule release in thrombus formation, demonstrating roles for VAMP-8 and VAMP-7 in platelet function during thrombus formation.