Matrix Metalloproteinases in Angiogenesis and Inflammation

The vasculature optimally delivers nutrients and oxygen to the organism by adaptation of endothelial cells to context-dependent needs resulting in a high degree of vascular heterogeneity. However, the mechanisms that govern capillary remodelling in homeostasis or upon injury in different tissues are not well characterized. Our group is focused on the contribution of members of the membrane-type matrix metalloproteinases (MT-MMPs) to this process by playing both proteolytic and non-proteolytic actions on the cellular and peri-cellular milieus. Our recent data point indeed to distinct cellular distribution and context-dependent functions of MT-MMPs in the vasculature and underscore the in vivo heterogeneity of vascular responses to injury highlighting the need for tissue-tailored strategies to target selected molecular to improve tissue repair. We are offering two Master positions to:

1) elucidate new players in blood flow-regulated shaping of vascular networks in health and disease;

 2) characterize the regulation of the innate immune response and its cross-talk with the vasculature in disease.

We are using high- and super-resolution microscopy, 3D image analysis, proteomics, bioinformatics, protein modelling, lentiviral strategies and genetic mouse models to pursue these goals. We finally intend to apply this knowledge to develop novel angiotherapies aimed at improving capillary perfusion and tissue performance and enhancing innate immune responses in several pathophysiological contexts.