Regulation of vascular permeability and leukocyte extravasation in inflammation: mechanisms and heterogeneity in different organs

Principal investigator: Dietmar Vestweber
Project number: CRC 1450 B03
Project term: 01/2021–12/2024

It has recently emerged that the molecular mechanisms and requirements which control the integrity of the endothelial barrier vary significantly between different organs. This project will analyse how VE-cadherin regulates vascular permeability of the endothelium in different tissues (1, 2).

We will focus on the role of posttranslational modifications of certain residues for which we have or will generate and analyse point mutated knock-in mice (3). In a second part, it will be investigated whether the preferential use of the leukocyte diapedesis route through endothelium (trans-junctional versus transcellular) varies in different organs and which molecular mechanisms influence this choice (4). This will be analysed with the help of knock-in mice where due to directly fusing VE-cadherin with ɑ-catenin the trans-junctional pathway is blocked (5, 6).

Publications

The names of the principal investigators in our network have been bolded. Publications released prior to 2021, when funding for our network commenced, represent previous project-related work.