James Mcfadyen

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The Dok proteins are a family of adaptor molecules that have a well defined role in regulating cellular migration, immune responses, and tumor progression. Previous studies have demonstrated that Doks-1 to 3 are expressed in platelets and that Dok-2 is tyrosine-phosphorylated downstream of integrin αIIbβ3, raising the possibility that it participates in(More)
PI3KC2α is a broadly expressed lipid kinase with critical functions during embryonic development but poorly defined roles in adult physiology. Here we utilize multiple mouse genetic models to uncover a role for PI3KC2α in regulating the internal membrane reserve structure of megakaryocytes (demarcation membrane system) and platelets (open canalicular(More)
Although the role of platelets as central mediators of hemostasis and thrombosis has been the primary focus of research into platelet biology for more than a century, over the last decade, nonhemostatic functions of platelets have been increasingly defined. As such, a large body of experimental evidence now exists, which places the platelet as a key player(More)
Gut ischemia is common in critically ill patients, promoting thrombosis and inflammation in distant organs. The mechanisms linking hemodynamic changes in the gut to remote organ thrombosis remain ill-defined. We demonstrate that gut ischemia in the mouse induces a distinct pulmonary thrombotic disorder triggered by neutrophil macroaggregates. These(More)
Dear Editor, Profound changes in the haemostatic system occur in patients with thalassaemia major [1]. Although now recognised as a prothrombotic state, based on epidemiological data demonstrating that patients with thalassaemia major and intermedia have a higher than expected incidence of venous thromboembolic disease and arterial thrombosis [1, 2], it was(More)
Novel biomarkers that accurately report the risk of cardiovascular events such as myocardial infarction have long been sought after. This is driven by the need to inform clinical diagnostic pathways and to optimize therapeutic approaches with the ultimate aim of reducing cardiovascular mortality and morbidity. Technical advances in the sensitivity,(More)
The central role of platelets in the formation of the primary haemostatic plug as well as in the development of arterial thrombosis is well defined. In general, the molecular events underpinning these processes are broadly similar. Whilst it has long been known that disturbances in blood flow, changes in platelet reactivity and enhanced coagulation(More)