Research Interests

How does the vasculature acquire its stereotypical anatomy?
Blood vessels form during embryogenesis, acquiring a reproducible and pervasive anatomy highly conserved among vertebrates. This reproducibility is essential for survival and homeostasis, and ensures that all tissues of the body receive and exchange gases, hormones, metabolic wastes and immunity factors.
Our lab studies the genetic and cellular mechanisms that shape the anatomy of the vasculature. To achieve this, we use the transparent zebrafish as a model system. We use transgenic animals with fluorescent blood vessels to visualize in vivo and in real time the developing endothelium.
Studying the mechanisms that shape the anatomy of the vasculature is important for human health. Congenital conditions affecting the formation of the blood vessels (such as vascular malformations) or acquired conditions affecting vascular function (i.e. stroke) have serious to devastating health consequences. Furthermore, novel molecules with vascular roles are pharmacological targets with therapeutic applications in the treatment of cancer and ischemia.

Specific areas of interest

1. Semaphorin-PlexinD1 signaling

We have shown that that ligands of the Semaphorin (Sema) family are secreted by the somites and serve as repelling guidance cues for navigating intersomitic vessels expressing the endothelial-specific, cell surface receptor PlexinD1. However, the molecular mechanisms by which the PlxnD1 receptor regulates endothelial pathfinding and behavior are not known. We have isolated a variety of proteins that associate with the intracellular part of the PlxnD1 receptor and as such are candidates for mediating its function. We are currently investigating their functional role during vascular patterning.

2. Uncovering novel pathways that regulate vascular patterning

Lack of plxnD1 activity induces defects only in some vessels, suggesting that additional signaling cascades are required to pattern the vasculature. To uncover them, we are mapping and characterizing novel mutants with abnormal vessels.
For instance, the cerebral blood vessels are missing in the mutant no food for thought, while misguided trunk vessels are found in road to perdition animals. By studying these mutants, we will gain insights into how different areas of the body acquire their specific vascular anatomies and why vascular disorders display local-specificity. It is likely that these mutants will serve as models for human diseases such as stroke and vascular malformations.

3. Development of novel transgenic tools for vascular development studies

Our studies, as well as the findings from others suggest that a dynamic molecular landscape of different spatially restricted cues guides the formation of the vascular tree. To aid us in understanding this process, we require both misexpression tools and tissue-specific reporters. We are developing these technologies to complement our Semaphorin-PlexinD1 signaling and mutant characterization studies.