Endothelial cells (ECs), which line the inner surfaces of blood and lymphatic vessels, play a crucial role in maintaining tissue health, guiding organ formation during embryonic development, supporting tissue regeneration, and mediating responses to pathological conditions. Recent advances in single-cell technologies have revolutionized our understanding of EC heterogeneity. Nevertheless, the ways in which vessels communicate with their surrounding microenvironments across different tissues, vessel types, and pathophysiological states remain largely underexplored.

Over the past few years, my lab has used the zebrafish (ZF) model to investigate the molecular and cellular mechanisms controlling blood and lymphatic vessel formation, as well as the instructive role the vasculature plays during organogenesis. Our studies have uncovered unexpected developmental origins for lymphatic endothelial cells, challenged traditional models of lymphangiogenesis, and identified the molecular cues that drive organ-specific vascular networks in the liver, pancreas, and intestine. We have also revealed novel mechanisms of vascular plasticity, including blood vessel formation through lymphatic-to-blood endothelial transdifferentiation in the regenerating fin.

EC heterogeneity is highly relevant not only to organ growth and regeneration but also to vascular malformations and malfunctions of the cardiovascular system. It is within this context that we have established zebrafish models of vascular malformations. Leveraging the optical transparency, genetic accessibility, and suitability of zebrafish for high-throughput drug screening, we utilize this system to investigate disease mechanisms in vivo and to identify candidate therapeutic compounds. Finally, ECs represent the main component of stem cell niches, supporting their maintenance, expansion, and controlling their differentiation.

By defining the principles that govern endothelial specialization and plasticity, our research bridges the gap between fundamental vascular biology and translational applications, aiming to inform strategies for repairing and reprogramming vascular networks in disease.