Team 2


Thrombosis platelets and vascular diseases





Team members

New pathophysiologic pathways involved in thrombosis; from bedside to the bench

Pierre Morange

This topic aims to identify new pathophysiologic pathways involved in hemostasis and venous thrombosis (VT). We are using omic strategies in large patient cohorts. These cohorts are implemented with biobanks allowing the analysis of plasmatic and genetic markers. A pangenomic study allowed us to identify new genes associated with VT, genes that do not belong to the classical coagulation/fibrinolytic cascades, thus opening new paths to the discovery of new pathophysiologic pathways. Other omic approaches are ongoing in national and international networks.

Concerning the fundamental level, we are characterizing the newly discovered pathways and we are focusing our research on the role of unexplored transmembrane proteolysis in the regulation of hemostasis and thrombosis.

We are studying the CTL2 protein (choline transporter like protein-2) and its interaction with von Willebrand factor (VWF) in dynamic conditions but also using animal model of inflammation and thrombosis. This project is supported by a young researcher ANR grant. In parallel we have identified a protective role of the inflammatory molecule LIGHT (TNFSF14) during atherosclerosis and in the associated thrombotic complications. We are currently trying to decipher the molecular mechanisms involved by studying the role of LIGHT on the thrombogenicity of the atherosclerotic plaque and platelet reactivity.

We are interested in the proteases responsible for the cleavage of cell surface proteins. We are looking at different aspects of their regulation (synthesis, cellular trafficking, maturation, activation, membrane organization…) and also at the impact of their regulation on the cleavage of their substrate. We are also looking at the biologic and pathophysiologic consequences of these regulations. Thrombomodulin (TM) is a transmembrane protein, expressed at the vascular endothelial cell surface, that has antithrombotic properties. TM has been identified as a substrate of the intramembrane serine protease Rhomboid-like 2 (RHBDL2). We are studying the regulation of TM cleavage by RHBDL2 in the vascular endothelium and the consequences of this cleavage.

This work represents a unique opportunity to understand new mechanisms involved in thrombotic disorders in order to improve the diagnosis tools and therapies for patients suffering from TV.