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BMP9 & BMP10: two key players in vascular quiescence and rare vascular diseases (in english)


On February 1, 2024

Séminaire de Sabine Bailly (BAL team, Labo BioSanté, INSERM U1292, UGA et CEA Grenoble)

Vascular vessels play key roles in controlling oxygen and nutrient exchange and cellular trafficking between blood and the perfused organs. In adult, endothelial cells are quiescent. This vascular quiescence is regulated by organ-specific signaling pathways which can lead to many pathologies when dysfunctional (diabetes, age-related macular degeneration, ischemia, …). Our team works on of these signal pathways, the BMP (Bone morphogenetic proteins) signalling pathway whose mutations lead to a rare vascular disease called Hemorrhagic Hereditary Telangiectasia (HHT). This disease is due to loss-of-function of two transmembranous receptors ALK1 (activin receptor-like kinase 1) and endoglin. In 2007, our team identified the two high affinity ligands (BMP9 and BMP10) of this orphan signaling complex.  Since then, we have studied their roles using in vitro and in vivo models. We could show that this pathway plays a key role in vascular quiescence and could propose that this disease is due to an activation of vascular remodeling. In 2012, we performed the first clinical trial repurposing an anti-angiogenic drug (bevacizumab, an anti-VEGF antibody) that significantly ameliorated the symptoms of HHT patients which is still the best option for these patients. We have also developed functional tests for these mutant proteins that are now used in several hospitals and that allowed a better understanding of these proteins.

More recently, we have developed bulk and single cell RNAseq as well as phosphoproteomic approaches in control and mutated endothelial cells derived from patients as well as several inducible and tissue-specific knockout mouse models (Alk1, Bmp9 and Bmp10) in order to better understand the molecular mechanisms involved in this signaling pathway and angiogenesis and to propose new therapeutic strategies in HHT.

Sabine Bailly est invitée par Emmanuel Barbier.


On February 1, 2024
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Amphi Kampf

Submitted on January 31, 2024

Updated on January 31, 2024