Adding new branches to the vascular tree: organ-specific angiogenesis
| Dates: | 6 May 2014 |
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| Times: | 13:00 - 14:00 |
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| What is it: | Seminar |
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| Organiser: | Faculty of Life Sciences |
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| Who is it for: | University staff |
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| Speaker: | Ralf Adams |
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This seminar is part of the Tissue Systems seminar series. Abstract: Angiogenesis is the main process mediating the expansion of the blood vessel network during development, tissue regeneration or in pathological conditions such as cancer. The formation of new endothelial sprouts, a key step in the angiogenic growth program, involves the selection of endothelial tip cells, which are highly motile, extend numerous filopodia, and lead new sprouts. Key aspects of angiogenesis, such as endothelial proliferation and tip cell formation, are positively modulated by vascular endothelial growth factor (VEGF), whereas Notch and the ligand Dll4 are important negative regulators. Our work has identified the Notch ligand Jagged1 as a potent pro-angiogenic regulator with the opposite role as Dll4. We also found that blocking of Notch activity enables strong angiogenic growth even in mutant animals lacking endothelial VEGF receptor-2 expression, which could be relevant for resistance to anti-VEGF therapies. Ephrin-B2, a ligand for Eph family receptor tyrosine kinases, controls endothelial cell motility by modulating VEGF receptor endocytosis and the activation of downstream signal transduction cascades. Moreover, we found that the spatial pattern of VEGF endocytosis in growing vessels is controlled by the clathrin-associated sorting protein Dab2, the cell polarity protein PAR-3 and ephrin-B2, which cooperate to promote efficient expansion of the vascular network. Our recent work focuses on organ-dependent differences in vessel growth, the regulation of tissue patterning by blood vessel-derived signals, and the formation of endothelial cell-associated microenvironments.
Speaker
Ralf Adams
Organisation: Max Planck Institute for Molecular Biomedicine
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Lecture Theatre
Michael Smith Building
Manchester
