A major research topic of the group aims at understanding the cell biological principles that ensure intactness of blood vessels and that control leukocyte extravasation and vascular permeability in various pathological settings (Vestweber, 2015). Endothelial cells form the inner layer of the blood vessel wall and control when and where cellular and soluble components of the blood enter tissue. The junctions between endothelial cells are the central exit sites, which are opened either by inflammatory stimuli or directly by leukocytes that become captured to the luminal endothelial surface. We have shown recently that phosphorylation of certain tyrosine residues of VE-cadherin control this process in vivo(Wessel et al., 2014). Interestingly, different tyrosine residues were addressed by the induction of vascular permeability and the exit of leukocytes. This highlights the central role of VE-cadherin for each process in vivo and reveals that the stability of endothelial junctions and the function of VE-cadherin are differently affected by these two different patho-physiological processes.
Despite the central role of VE-cadherin for the integrity of the blood vessel wall, we found recently that induced gene-inactivation of VE-cadherin disrupted endothelial junctions only in some (heart, lung) but not in all organs (skin, brain)(Frye et al., 2015). In addition, this study revealed that the endothelial specific receptor type tyrosine phosphatase VE-PTP regulates endothelial junctions in vivo by regulating VE-cadherin adhesive function as well as by balancing the tyrosine kinase activity of Tie-2. The strong supportive effect of Tie-2 on junction stability makes the VE-PTP/Tie-2 complex a valuable target for therapeutic treatment of vascular leakiness(Shen et al., 2014).
In additional projects, we have analyzed how endothelial junctions control blood vessel development (Bentley et al., 2014), how platelets ensure blood vessel integrity during inflammation (Hillgruber et al., 2015) and how the activation of leukocytes and their integrins is controlled in the context of leukocyte recruitment into tissues (Artz et al., 2016) (Goswami et al., 2017).
- Sheikh, B.N., Guhathakurta, S., Tsang, T.H., Schwabenland, M., Renschler, G., Herquel, B., Bhardwaj, V., Holz, H., Stehle, T., Bondareva, O., Aizarani, N., Mossad, O., Kretz, O., Reichardt, W., Chatterjee, A., Braun, L.J., Thevenon, J., Sartelet, H., Blank, T., Grün, D., von Elverfeldt, D., Huber,T.B., Vestweber, D., Avilov, S., Prinz, M., Buescher, J.M. and Akhtar, A. (2020). Neural metabolic imbalance induced by MOF dysfunction triggers pericyte activation and breakdown of vasculature. Nat Cell Biol. / Online ahead of print.
- Braun, L.J., Stegmeyer, R., Schäfer, K., Volkery, S., Currie, S.M., Kempe, B., Nottebaum, A.F. and Vestweber,D. (2020).Platelets docking to VWF prevent leaks during leukocyte extravasation by stimulating Tie-2. Blood / Online ahead of print.
- Smith, R.O., Ninchoji, T., Gordon, E., André, H., Dejana, E., Vestweber, D., Kvanta, A. and Claesson-Welsh, L. (2020). Vascular permeability in retinopathy is regulated by VEGFR2 Y949 signaling to VE-cadherin. Elife / Apr 21;9:e54056.
- Owen-Woods, C., Joulia, R., Barkaway, A., Rolas, L., Ma, B., Nottebaum, A.F., Arkill, K.P., Stein, M., Girbl, T., Golding, M., Bates, D.O., Vestweber, D., Voisin, M.B. and Nourshargh, S. J. (2020). Local microvascular leakage promotes trafficking of activated neutrophils to remote organs. Clin Invest. /1;130/, 2301-2318.
- Samus, M., Li, Y.T., Sorokin, L., Rottner, K. and Vestweber, D. (2020). Actin-Binding Protein Cortactin Promotes Pathogenesis of Experimental Autoimmune Encephalomyelitis by Supporting Leukocyte Infiltration into the Central Nervous System. J Neurosci. / 12;40 / 1389-1404.
- Duong, C.N., Nottebaum, A.F., Butz, S., Volkery, S., Zeuschner, D., Stehling, M. and Vestweber, D. (2020). Interference With ESAM (Endothelial Cell-Selective Adhesion Molecule) Plus Vascular Endothelial-Cadherin Causes Immediate Lethality and Lung-Specific Blood Coagulation. Arterioscler Thromb Vasc Biol. /40(2) / 378-393.
- Thomson, B.R., Carota, I.A., Souma, T., Soman, S., Vestweber, D. and Quaggin, S.E. (2019). Targeting the vascular-specific phosphatase PTPRB protects against retinal ganglion cell loss in a pre-clinical model of glaucoma. Elife / 17;8 / e48474.
- Li, Y.T., Goswami, D., Follmer, M., Artz, A., Pacheco-Blanco, M. and Vestweber, D. (2019). Blood flow guides sequential support of neutrophil arrest and diapedesis by PILR-β1 and PILR-α. Elife / 6;8 / e47642.
- Braun, L.J., Zinnhardt, M., Vockel, M., Drexler, H.C., Peters, K. and Vestweber, D. (2019). VE-PTP inhibition stabilizes endothelial junctions by activating FGD5. EMBO Rep. /20(7) / e47046.