Lu Wang Email & Phone Number

Thesis topic: The role of thiol isomerase ERp57 and ERp72 in thrombosis and platelet activation and the underlying mechanism.In this study, we found both ERp57 and ERp72 are important in platelet activation and thrombosis. For ERp57, we used platelet specific-ERp57 knock out mice and found 1) platelet-derived ERp57 regulates platelets accumulation in a integrin IIb3-dependent manner in FeCl3-induced mesenteric arteriole thrombosis model; 2) ERp57 regulates integrin IIb3 activation and IIb3-mediated platelet function; 3)ERp57 directly interacts with platelet surface IIb3 integrin during activation of the receptor; 4) using ERp57 mutant protein, we found the C-terminal CGHC motif of ERp57 is critical for platelet aggregation; 5) using sulfhydryl labeling and Western blotting, we found ERp57 catalyzes disulfides reduction in IIb3 molecule.For ERp72, using anti-ERp72 antibody, we found 1)ERp72 regulates platelet activation, thrombosis and hemostasis; 2)the second and third CGHC active motifs are important in platelet aggregation; 3) ERp72 binds to IIb3 and catalyzes disulfides reduction in IIb3. 4)ERp72 and ERp57 act seperately in platelet aggregation may catalyze different reactions in aIIbb3. Finally, we found some cysteines in aIIbb3 are important during platelet activation by using sulfhydryl labeling and mass spectrometry,