"Understanding angiogenesis through multispectral genetic mosaics" will feature Dr. Rui Benedito from CNIC in the Department of Cell and Developmental Biology.
Rui Benedito graduated in Microbiology and Genetics and then did his PhD at the University of Lisbon where he became interested in mouse genetics and developmental vascular biology. He then moved to the United Kingdom where he did a Postdoc at the London Research Institute under the supervision of Dr. Ralf Adams. His work in this period focused on understanding the roles of the different Notch ligands and modulators in angiogenesis. Later he moved to the Max Planck Institute for Molecular Biomedicine where he identified several other molecular mechanisms that regulate angiogenesis when VEGF signalling is blocked, which has implications for the design of therapies targeting angiogenesis. After his postdoctoral studies, he started his research group at the National Center for Cardiovascular Research in Spain (CNIC). His group has developed genetic technology of broad interest and is using it to understand the biology of blood vessels at high resolution in different developmental and disease contexts. This knowledge can be later used to develop better strategies to target blood vessels in cancer and cardiovascular disease.
Our lab has been studying how the Notch and VEGF signalling pathways control angiogenesis by using new genetic methods that enable multispectral barcoding of single cells and functional mosaic genetics (ifgMosaics, Cell 2017 and iFlpMosaics, Nature 2021). We have used these methods to understand how endothelial cells (ECs) with different Notch, VEGF, Myc and MAPK signalling levels clonally expand and differentiate over time, and how these molecular mechanisms regulate the formation of endothelial tip, stalk, arterial and venous cells. We found that ECs experiencing very high mitogenic stimulus become arrested during angiogenesis, which limits the effectiveness of pro-angiogenic therapies (NCOMM, 2019). More recently, we found that arterialization requires the timely supression of cell growth, independently of the function of genetic pathways promoting arterial genetic identity (Nature, 2021). We will present data showing the use of multiple functional genetic mosaic systems to understand with high genetic accuracy how cells with different mitogenic and metabolic activities clonally expand and segregate over time to different positions of a growing angiogenic network.
Link for the paper: https://www.nature.com/articles/s41586-020-3018-x