Tumor Angiogenesis

Title: Understanding the role of hypoxia in the regulation of angiogenesis

Angiogenesis is a fundamental process that leads to the formation of new blood vessels from pre-existing ones. It is a very active mechanism during development, yet it is highly restricted in adult tissues and aberrantly activated in cancer. Hypoxia is one of the main triggers of angiogenesis both in physiology and disease. In response to proangiogenic stimuli like hypoxia, quiescent endothelial cells (ECs) are activated and reprogrammed to two distinct phenotypes: tip ECs and stalk ECs. Tip cells are cell cycle arrested and extend long filopodia to sense and direct the migration of the sprouting vessels towards the proangiogenic stimulus. In contrast, stalk cells are proliferative cells that provide new endothelial cells to the expanding vessels. The role of Hypoxia Inducible Factors (HIF) in reprogramming endothelial cell fate during sprouting angiogenesis has not been fully elucidated. The aim of our research project is to better understand the role of hypoxia in the regulation of the proliferative response of endothelial cells and in the reprogramming of endothelial cell fate during sprouting angiogenesis. For this purpose we use angiogenesis models based on embryoid bodies generated from mouse stem cells. We employ a combination of Cellular and Molecular Biology approaches to understand how the proliferative response of endothelial cells is modulated during vessel formation under hypoxic conditions.