Nigel Mackman,
Distinguished Professor of Medicine,
University of North Carolina at Chapel Hill
Dr. Mackman began his scientific career studying the role of Escherichia coli hemolysin toxin in bacterial pathogenesis. He received a PhD from the University of Leicester. In 1987 he moved to The Scripps Research Institute in California as a postdoctoral fellow to study blood coagulation and rose to the rank of Associate Professor with tenure. In 2007, Dr. Mackman moved to the University of North Carolina at Chapel Hill to become the John C. Parker Distinguished Professor in Medicine. His research has focused on the roles of tissue factor, coagulation proteases, protease activated receptors, extracellular vesicles, thrombosis, inflammation, ischemia-reperfusion injury, cancer, sickle cell disease, obesity, viral infection and atherosclerosis. In 2009 he presented the Sol Sherry Lecture on Thrombosis. He has chaired the Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) Council of the American Heart Association, and in 2010 chaired the Hemostasis Gordon Research Conference. In 2015 he received a Distinguished Scientist Award from the International Society of Thrombosis and Hemostasis. Dr. Mackman has served as an Associate Editor for Thrombosis & Hemostasis and the Journal of Thrombosis and Hemostasis, and is currently an Associate Editor for the Journal of Clinical Investigation and a Senior Associate Editor for ATVB. In 2017 he received an ATVB Distinguished Achievement Award.
Procoagulant Extracellular Vesicles in Hemostasis and Thrombosis
Tuesday, 26 September 2017 at 10:45
Add to Calendar ▼2017-09-26 10:45:002017-09-26 11:45:00Europe/LondonProcoagulant Extracellular Vesicles in Hemostasis and ThrombosisExtracellular Vesicles 2017 in Cripps Court, Magdalene College, Cambridge, UKCripps Court, Magdalene College, Cambridge, UKSELECTBIOenquiries@selectbiosciences.com
The coagulation cascade consists of a series of cofactor/protease complexes (tissue factor (TF)/FVIIa; FVIIIa/FIXa; FVa/FXa) that assemble on membrane surfaces and result in the formation of fibrin. TF is a transmembrane receptor for FVII/FVIIa and the TF/FVIIa complex is the major initiator of the clotting cascade. The clotting cascade plays an essential role in hemostasis but also contributes to pathologic thrombosis. Several coagulation proteases (FIX, FX, FVII and prothrombin) contain a Gla domain that is positively-charged. Normal cells have an asymmetric membrane with negatively-charged phospholipids, such as phosphatidylserine (PS), located on the inner leaflet of the membrane. However, after cell damage PS flips to the outer leaflet of the membrane where it facilitates the binding and assembly of Gla-containing coagulation proteases and activation of coagulation at sites of injury. Extracellular vesicles (EVs) are small vesicles derived from activated or apoptotic cells. There are several types of EVs that can enhance coagulation depending on the presence of exposed PS and TF. For instance, PS-,TF- EVs have the lowest procoagulant activity (PCA) whereas PS+,TF+ EVs have the highest PCA. The majority of EVs in blood are derived from platelets and were originally described as platelet dust. These PS+ and PS-EVs can enhance ongoing coagulation but cannot trigger coagulation. In contrast, EVs derived from activated monocytes and many types of tumors express PS and TF and can activate coagulation. PS+,TF+ EVs have been detected in the blood of patients with experimental endotoxemia, liver injury, cirrhosis, sickle cell disease, influenza A infection and cancer. These EVs likely contribute to thrombosis in these patients. Several prospective studies found that increased levels of TF+ EV precede venous thrombosis in pancreatic cancer patients. These studies suggest that TF+EVs could be used as a biomarker to identify patients at increased risk for venous thrombosis.
Add to Calendar ▼2017-09-26 10:45:002017-09-26 11:45:00Europe/LondonProcoagulant Extracellular Vesicles in Hemostasis and ThrombosisExtracellular Vesicles 2017 in Cripps Court, Magdalene College, Cambridge, UKCripps Court, Magdalene College, Cambridge, UKSELECTBIOenquiries@selectbiosciences.com
