Specialization
Focus of research
Regulation of microvascular integrity
The integrity of the vascular wall is dependent on proper cell-cell contact between endothelial cells. This cell-cell contact is mediated by VE (Vascular Endothelial)-cadherin (Cadherin-5, CD144), a calcium-dependent homotypic adhesion molecule. The adhesive function of VE-cadherin is regulated in a dynamic fashion by both extracellular stimuli (VEGF, TNF, thrombin, as well as vessel wall stiffness, etc) and intracellular signalling. For the regulation of VE-cadherin, its link to the actin cytoskeleton, via its intracellular domain, is essential.
To increase our molecular insights in these events, our group focuses on the regulation of actin dynamics in the context of endothelial integrity. We are particularly interested in the role and regulation of Rho-like GTPases. We use a range of in vitro approaches including biochemical assays, high resolution imaging and electrical resistance measurements of endothelial monolayers. Recently, we identified several ubiquitin ligases that specifically regulate Rho proteins and, in this way, control endothelial integrity. We have more recently shown that in particular the GTPase RhoB is controlled by synthesis and degradation and behave, when expressed, as a constitutively active GTPase.
This work is now taken further in a collaboration with a computational analysis group from the UvA (PI, prof Hoekstra) to see if we can model in vitro and in silico the diferet meachisms that control GTPase signaling and integrity in human endothelium.
3D microvessels
A related project has been focused on the use of self-organizing 3D microvessels - generated in a commercial 'chip'- to study iPSC-derived endothelial and smooth muscle cells in various contexts.
Academic profile
Lines of research: RhoGTPase regulation and -signalling in endothelial cell-cell adhesion and inflammation has been the major theme of my research over the past 20+ years. As a LSBR-fellow (Landsteiner Foundation) and founder and chair of the department of Molecular Cell Biology at Sanquin Research (2000-2015), I focused on signalling that controls leukocyte-endothelial interactions and transendothelial migration, building a successful and internationally recognized line of research. Since 2015, my work continued AmsterdamUMC focusing on the role of Rho GTPase post-translational
modifications, mainly ubiquitination, in the regulation of vascular endothelial integrity. My group identified the key ubiquitin ligase that controls degradation of the RhoB GTPase and protects VE-cadherin-mediated cell-cell contact and barrier function in quiescent EC. My group collaborates regularly with (clinical) groups on studies of microvascular integrity and –disease. I was appointed full professor at the University of Amsterdam in 2011 and at the Free University (Amsterdam) in 2018. My research is and has been funded by the LSBR, ZonMW and NWO.
Supervision of students, academic and non-academic staff:
Among the undergraduate and graduate students trained in my lab over the years, there are many that have continued their career in science. My lab alumni include recipients of personal grants in various schemes, including ZonMW-Veni, Vidi and Vici, as well as of LSBR- and Dekker fellowships (personal grants, Dutch Heart Foundation).
Several former PhD students have been appointed full professor at Dutch universities. In addition, many former PhD students have continued their career in the (pharmaceutical) industry, within the Netherlands and abroad. My commitment to supporting young researchers is also evident from their position as senior author on publications from my group. This helps them in the competition for personal grants, which is essential in an early career stage.
In addition to the supervision of (clinical and pre-clinical) PhD students and postdocs, I mentor, on average, >5 undergraduate students/year (internships, theses etc.) and teach vascular physiology, cardiovascular disease at Amsterdam UMC, VU, and Amsterdam University College. In addition, I’m involved in specific academic training
programs of bachelor- and master- as well as PhD-students.
Administrative and managerial tasks: (i) PI of research team supervising PhD students, post-docs and junior faculty (1998-present); (ii) Chair of the dept. of Molecular Cell Biology and member of the research board at Sanquin Research (2000-2015); (iii) vice-chair of the dept. of Physiology, Amsterdam UMC (2015-present); (iv) Chair of the Animal Experiments Committee (DEC) of the Academic Medical Centre (2015-2020); (v) scientific director of the Animal Research Centre of the VU Amsterdam (2016-2021); (vi) chair of the examination committee of the Faculty of Medicine, VU Amsterdam (2021-present).
Membership of scientific boards, editorial boards, and committees: I have been member of the Junior Dekker grant selection committee of the Dutch Heart Foundation (2012-2018); I am currently member of selection boards for talent- and tenure track programs within Amsterdam UMC and for international funding committees (ERC Advanced, ANP). Moreover, I’ve been a member of the editorial board for the Amsterdam UMC Research Code on research ethics and integrity. Finally, I have been program leader of the innovation section ‘Microcirculation’ of the Cardiovascular
Research Centre at AmsterdamUMC until summer 2025 and member of the ACS directorate.