血栓形成是血小板活化和凝血系统激活导致的血液凝固，其启动机制尚不清楚。二硫键异构酶（PDI）家族调控功能性蛋白二硫键的氧化还原，该家族有20个成员。我们近来报道，该家族中的ERp57和PDI参与血栓形成过程，但是其它成员在血栓形成中的作用不清楚。我们最近的研究发现，ERp72调控体内血小板积聚及纤维蛋白形成，且ERp72在血小板活化中比PDI和ERp57发挥更重要的作用，结果提示ERp72通过双重调控血小板活化和凝血系统激活在血栓形成中发挥重要作用。为剖析ERp72在体内血栓形成中调控血小板活化和凝血系统激活的细胞与分子机制，我们将应用ERp72组织特异性基因敲除小鼠模型、活体成像血栓形成模型、血小板聚集、流式细胞术、质谱分析和凝血酶生成等综合手段。本项目旨在明确ERp72在血栓形成中的重要作用和机制，为阐明血栓形成的启动机制提供新的突破性认识，并推动以ERp72为靶点的抗血栓药物的研发。

Thrombosis is an integrated process of platelet activation and coagulation, its mechanism remains elusive. The family of protein disulfide isomerases（PDIs）includes 20 members of thiol isomerases that regulate the activities of functional proteins via redox control of their thiol-disulfide exchange. Recently we have reported that PDI and ERp57 of this family play an important role in thrombosis, however, the roles of other members of PDI family still remain unknown. Our recent preliminary studies suggest that ERp72 plays a more important role than PDI and ERp57 in platelet activation, and it also regulates the platelet accumulation and fibrin deposition in vivo. Thus, ERp72 mediates thrombosis by dual regulation of platelet activation and coagulation. To determine the cellular and molecular mechanisms underlying the role of ERp72 in thrombosis, we will utilize tissue-specific ERp72-deficient mouse model, in vivo thrombosis model, platelet aggregation, flow cytometry, mass spectrometry and thrombin generation assays. Therefore, our studies will not only reveal the novel mechanism for thrombosis, but will also identify new therapeutic target for antithrombotic treatment.