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Ralf H. Adams

Max-Planck-Institute, Münster

Wednesday, October 23, 15:10 - 15:35

Molecular regulation of angiogenic blood vessel growth

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.

Biography

Ralf H. Adams did his Ph. D training at the Max Planck Institute for Brain Research before he joined the laboratory of Rüdiger Klein at EMBL in 1996. In 2000, he started his own research group at the Cancer Research UK London Research Institute. Since he has moved as Director to the Max Planck Institute for Molecular Biomedicine and Professor the University of Münster in 2008, Ralf Adams and his group have continued to provide insight into key processes controlling developmental blood vessel growth and, in particular, its regulation by Notch, VEGF and Eph/ephrin signaling.

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