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Microvascular Development and Vascular Permeability
Our laboratory studies how growing blood vessels integrate into their host organs without disrupting the organisation and function of other cell types. To achieve this goal, we combine reverse genetics and tissue culture models to define the precise role of signalling pathways implicated in vascular growth and patterning, with particular emphasis on the isoforms of the main vascular growth factor VEGF and their receptors. In complementary approaches, we investigate the role of VEGF signalling in developing neurons and vascular pathologies of the nervous system.
Key research activities
VEGF is essential for angiogenesis in development and
neoangiogenesis in ischemic pathologies. In adults, it additionally regulates
vascular permeability. Our previous research revealed that the differential
matrix affinity of VEGF isoforms promotes the formation of chemotactic
gradients that guide sprouting vessels to sites of VEGF expression. Current research
in the lab seeks to define the signalling pathways that distinguish angiogenic
from permeability signalling pathways to open up new avenues for targeted
receptor NRP1 binds both class 3 semaphorins and the VEGF164 isoform of VEGF.
We previously reported that semaphorin signalling through NRP1 is dispensable
for vascular development, but that VEGF164 signalling through NRP1 regulates neuronal
migration, survival and commissural axon guidance and cooperates with neural
semaphorin signalling to orchestrate the formation of specific neuronal
systems. Current research seeks to define the signalling pathways that convey
VEGF164/NRP1 signals in neurons and their progenitors.
We previously showed that VEGF-mediated vessel sprouting synergises with macrophage-promoted sprout fusion to build precisely patterned vessel networks. Current research in the lab seeks to elucidate the molecular mechanisms of macrophage-endothelial cell interactions and the contribution of myeloid cell populations to neoangiogenesis and VEGF-mediated vascular permeability.