New MarMaRa Teams

New pathophysiological mechanisms involved in thrombosis: from the clinic to the laboratory

Pierre Morange's team

Pierre Morange's team explores new pathophysiological avenues linked to hemostasis and venous thrombosis (VT), combining clinical and fundamental research. Thanks to "omics" approaches applied to large cohorts of patients, enriched by biobanks, it has identified new genes associated with VT. These genes, which are not part of the classical coagulation or fibrinolysis cascades, open the way to novel discoveries about the underlying mechanisms.

In the laboratory, the team studies little-explored processes, such as transmembrane proteolysis, in the regulation of hemostasis and thrombosis. Among its flagship projects are the study of the CTL2 protein and its interaction with von Willebrand factor (VWF) in models of inflammation and thrombosis, and the analysis of the protective role of the inflammatory molecule LIGHT in atherosclerosis and its thrombotic complications.

The team is also interested in the proteases that cleave proteins on the cell surface, exploring their regulation and biological impact. For example, it is studying thrombomodulin (TM), an antithrombotic protein, and its cleavage by a specific protease, RHBDL2, in vascular endothelial cells.

This ambitious research is aimed at gaining a better understanding of the mechanisms of thrombotic diseases, and developing new diagnostic tools and innovative therapies for patients.

Stéphane Coulon's team joins our Institute with a research focus on telomeres and chromatin

We are delighted to welcome Stéphane Coulon's team, specialists in telomere maintenance mechanisms, structures essential to genome stability and function. This work is at the crossroads of cancer, aging and rare genetic diseases.

The team's research aims to understand how telomeres, located at the ends of chromosomes, are maintained and protected. Erosion or dysfunction of these structures is associated with processes such as cellular aging, age-related diseases, stem cell biology, as well as the development of certain cancers.

Using yeast models, the team is exploring the mechanisms that regulate telomere length, telomere replication and cellular responses to telomere erosion. Particular attention is paid to the relocation of eroded telomeres to the nuclear pore during replicative senescence, and to the consequences of this phenomenon.

In addition, the team is involved in a consortium identifying the genes responsible for telomere biology disorders, rare genetic diseases caused by premature telomere shortening. This research aims to better understand their role in telomere maintenance.

Finally, the team is contributing to several anticancer programs, notably on the mechanisms of Alternative Lengtheningof Telomeres (ALT) in mesenchymal tumors without ATRX mutations. This work paves the way for new therapeutic approaches against cancer.

These lines of research enrich our institute, strengthening our expertise in key areas of fundamental biology and human health.

The "Evolutionary Genetics, Red Globules, Biotherapy" (GENGLOBE) team joins our institute

Led by Wassim El Nemer, the GENGLOBE team explores the evolutionary and functional aspects of human genetic diversity. It focuses on the study of normal and pathological red blood cells and blood groups, and their role in biotherapy approaches.

Thanks to a multidisciplinary approach and unique access to biological collections and rare blood samples, resulting from their collaboration with the Établissement Français du Sang and clinical teams, the team structures its research around three main axes:

• Human demographic and adaptive history: understanding human evolution through genetic markers.
• Red cell biology and genetic diseases: studying red cell-related mechanisms in normal and pathological contexts.
• Immunogenic polymorphism and implications for biotherapy: analyze blood group variations and their impact on therapeutic strategies.

This work, at the interface between evolutionary genetics and medicine, enriches our institute through its fundamental scope and innovative clinical implications.