Our group is part of the department of Molecular Cell Biology of Sanquin Research and Landsteiner Laboratory in Amsterdam, the Netherlands. Our institute has a strong collaboration with the Academic Medical Center (AMC) in Amsterdam and the University of Amsterdam (UvA). (www.mcb.sanquin.nl). Within our group, there are projects available for undergraduate students to carry out their internship. Please find the link at the left under "Trainee Projects". If you are interested click on the "Contact" link at the left.
The research in our group focuses on the interaction between the endothelial cell and the leukocyte. We are primarily interested in how leukocytes cross the endothelium, and what the contribution of the endothelium is during this process. This process of extravasation requires integrin-mediated adhesion to endothelial adhesion receptors such as ICAM-1. Upon binding and clustering of ICAM-1, the small GTPases RhoA and Rac1 are activated, which induce endothelial cell shape changes to allow passage of transmigrating leukocytes. In addition, we have demonstrated that another Rho family GTPase, RhoG, is activated after ICAM-1 engagement, controlling the formation of endothelial apical cup structures that surround adhering and transmigrating leukocytes. However, the signalling pathways that are triggered downstream of ICAM-1 leading to the activation of these small GTPases remain largely unclear. Below a schematic overview of the differnet pathways that can occur upon leukocyte adhesion can be found.
The junctional protein VE-cadherin regulates the integrity of the endothelial monolayer. VE-cadherin also controls the passage of leukocytes through the cell-cell junctions. Therefore, our other research line focuses how VE-cadherin mediates leukocyte extravasation in detail.
Our future research is aimed to understanding the endothelial signalling that is induced by adherent leukocytes in detail.
To study our goals, we make use of biochemical pull down assays, to measure GTPase or GEF activity. Also, using magnetic beads, we study the clustering of adhesion molecules such as ICAM-1. and with confocal scanning laser as well as the electron microscope. To study the crossing of leukocytes over endothelial monolayers, we use transmigration under flow assays.Find them in under "Protocols".