MTZ®-MPI-Award 2024 to Jonas Stewen

In our bodies, blood vessels undergo significant changes during development to ensure that oxygen and nutrients reach every tissue. This intricate process involves the careful formation of arteries and veins, which need to develop distinct networks. Hence, understanding how cells decide whether to become part of an artery or a vein is crucial for our health. In his doctoral research, Jonas Stewen explored the molecular mechanisms guiding these decisions, focusing on the interplay between two key molecules: EphB4 and ephrin-B2.

EphB4 is a receptor protein primarily found in veins, while ephrin-B2 is a ligand protein dominant in arteries. However, both molecules can be present in endothelial tip cells, which lead the expansion of the vascular system. In his work, Jonas Stewen discovered that EphB4 and ephrin-B2 regulate each other: when ephrin-B2 levels are high and EphB4 levels are low, tip cells switch to the arterial fate and develop into arteries.

Moreover, the work discovered that the interaction between EphB4 and ephrin-B2 impacts key signaling pathways, including the Notch and VEGF pathways, both of which are known to influence the development of arteries. “When ephrin-B2 is upregulated due to the loss of EphB4, it enhances the activity of these pathways, pushing the cells toward an arterial identity,” Stewen says. This interplay not only affects how the cells behave but also shapes the overall structure of the vascular system.

The implications of these findings are profound. Disrupting the balance between EphB4 and ephrin-B2 can lead to vascular malformations, such as arteriovenous crossings, where arteries improperly overlap with veins. This condition is associated with various health issues, including increased risk of stroke. The research suggests that a better understanding of these molecular mechanisms could lead to new treatments for vascular malformations and related diseases.