A5072849388- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Angiogenesis and VEGF in Cancer
- Hippo pathway signaling and YAP/TAZ
- Protease and Inhibitor Mechanisms
- 3D Printing in Biomedical Research
- Caveolin-1 and cellular processes
- Retinal Diseases and Treatments
- COVID-19 Clinical Research Studies
- Wnt/β-catenin signaling in development and cancer
- Glaucoma and retinal disorders
- SARS-CoV-2 and COVID-19 Research
- Microtubule and mitosis dynamics
- Long-Term Effects of COVID-19
- Immune cells in cancer
- Vascular Malformations and Hemangiomas
- Heat shock proteins research
- Retinopathy of Prematurity Studies
- Axon Guidance and Neuronal Signaling
- Cell death mechanisms and regulation
- Immune Response and Inflammation
- Cancer Cells and Metastasis
- Vascular Malformations Diagnosis and Treatment
- thermodynamics and calorimetric analyses
The University of Queensland
2018-2024
Sanquin
2016-2021
University of Amsterdam
2016-2021
Centre for Advanced Microscopy
2021
Amsterdam UMC Location University of Amsterdam
2016-2018
Thrombotic and microvascular complications are frequently seen in deceased COVID-19 patients. However, whether this is caused by direct viral infection of the endothelium or inflammation-induced endothelial activation remains highly contentious.Here, we use patient autopsy samples, primary human cells an vitro model pulmonary epithelial-endothelial cell barrier.We show that express very low levels SARS-CoV-2 receptor ACE2 protease TMPRSS2, which blocks their capacity for productive...
Abstract During immune surveillance and inflammation, leukocytes exit the vasculature through transient openings in endothelium without causing plasma leakage. However, exact mechanisms behind this intriguing phenomenon are still unknown. Here we report that maintenance of endothelial barrier integrity during leukocyte diapedesis requires local RhoA cycling. Endothelial depletion vitro or Rho inhibition vivo provokes neutrophil-induced vascular leakage manifests physical movement neutrophils...
Vascular endothelial (VE)-cadherin in adherens junctions is an essential component of the vascular barrier, critical for tissue homeostasis and implicated diseases such as cancer retinopathies. Inhibitors Src cytoplasmic tyrosine kinase have been applied to suppress VE-cadherin phosphorylation prevent excessive leakage, edema high interstitial pressure. Here we show that Src-related Yes kinase, rather than Src, localized at cell (EC) where it becomes activated a flow-dependent manner....
Endothelial YAP/TAZ (YAP is also known as YAP1, and TAZ WWTR1) signaling crucial for sprouting angiogenesis vascular homeostasis. However, the underlying molecular mechanisms that explain how control vasculature remain unclear. This study reveals focal adhesion protein deleted-in-liver-cancer 1 (DLC1) a direct transcriptional target of activated YAP/TAZ-TEAD complex. We find substrate stiffening VEGF stimuli promote expression DLC1 in endothelial cells. In turn, levels are YAP dependent,...
Upon inflammation, leukocytes rapidly transmigrate across the endothelium to enter inflamed tissue. Evidence accumulates that use preferred exit sites, alhough it is not yet clear how these hotspots in are defined and they recognized by leukocyte. Using lattice light sheet microscopy, we discovered prefer endothelial membrane protrusions at cell junctions for transmigration. Phenotypically, junctional present an asymmetric manner, meaning one shows protrusion adjacent does not. Consequently,...
Leukocytes follow the well-defined steps of rolling, spreading, and crawling prior to diapedesis through endothelial cells (ECs). We found increased expression DLC-1 in stiffness-associated diseases like atherosclerosis pulmonary arterial hypertension. Depletion ECs cultured on stiff substrates drastically reduced cell stiffness mimicked leukocyte transmigration kinetics observed for soft substrates. Mechanistic studies revealed that DLC-1-depleted or failed recruit actin-adaptor proteins...
Endothelial cell adhesion is implicated in blood vessel sprout formation, yet how controls angiogenesis, and whether it occurs via rapid remodeling of adherens junctions or focal assembly, both, remains poorly understood. Furthermore, endothelial controlled particular tissues under different conditions unexplored. Here, we have identified an unexpected role for spatiotemporal c-Src activity sprouting angiogenesis the retina, which contrast to dominant focus on maintenance vascular integrity....
Endothelial cells lining the blood vessel wall communicate intricately with surrounding extracellular matrix, translating mechanical cues into biochemical signals. Moreover, vessels require capability to enzymatically degrade matrix them, facilitate vascular expansion. c-Src plays a key role in growth, its loss endothelium reducing sprouting and focal adhesion signalling. Here, we show that constitutive activation of endothelial results rapid expansion, operating independently growth factor...
ABSTRACT Objectives Thrombotic and microvascular complications are frequently seen in deceased COVID-19 patients. However, whether this is caused by direct viral infection of the endothelium or inflammation-induced endothelial activation remains highly contentious. Methods Here, we use patient autopsy samples, primary human cells an vitro model pulmonary epithelial-endothelial cell barrier to show that express very low levels SARS-CoV-2 receptor ACE2 protease TMPRSS2. Results Accordingly,...
An inflammatory response requires leukocytes to migrate from the circulation across vascular lining into tissue clear invading pathogen. Whereas a lot of attention is focused on how make their way through endothelial monolayer, it less underneath endothelium before they enter tissue. Upon finalization diapedesis step, reside in subendothelial space and encounter focal adhesions. Using TIRF microscopy, we show that neutrophils navigate around these Neutrophils recognize adhesions as physical...
Active remodeling of the actin cytoskeleton in endothelial cells is necessary for allowing leukocytes to cross barrier during process transendothelial migration (TEM). Involvement RhoGTPases regulate organization inevitable, and we recently reported on local function RhoA limiting vascular leakage leukocyte TEM. As a follow-up investigated here possible involvement two other closely-related GTPases; RhoB RhoC, regulating TEM maintenance. Physiological flow experiments showed no substantial...
SUMMARY Adherens junctions allow cell contact to inhibit epithelial migration. But a long-standing puzzle is how locomotion downregulated when E-cadherin adhesions form at surfaces perpendicular, but not those parallel, the direction of We now show that this arises from coupling between and retrograde cortical flows leader cells in migrating epithelia. At interfaces perpendicular motion, such are antiparallel, which generates tensile signal induces actin-binding domain α-catenin promote...
Abstract Introduction Vascular retinopathy, characterised by abnormal blood vessel growth in the retina, frequently results vision impairment or loss. Neovascular tufts, a distinctive pathological feature of this condition, are highly leaky structures, exacerbating secondary complications. Despite their clinical significance, mechanisms underlying tuft development not fully elucidated, posing challenges for effective management and treatment vascular retinopathy. In study, we investigate...
Abstract Upon inflammation, leukocytes rapidly transmigrate across the endothelium to enter inflamed tissue. Evidence accumulates that use preferred exit sites, though it is not yet clear how these hotspots in are defined and they recognized by leukocyte. Using lattice light sheet microscopy, we discovered prefer endothelial membrane protrusions at cell junctions for transmigration. Phenotypically, junctional present an asymmetric manner, meaning one shows protrusion adjacent does not....
Abstract Endothelial cells lining the blood vessel wall communicate intricately with surrounding extracellular matrix, translating mechanical cues into biochemical signals. Moreover, vessels require capability to enzymatically degrade matrix them, facilitate vascular expansion. c-Src plays a key role in growth, its loss endothelium reducing sprouting and focal adhesion signalling. Here, we show that constitutive activation of endothelial results rapid expansion, operating independently...
Adherens junctions (AJs) are multi-protein adhesion structures that couple contractile actomyosin networks of epithelial cells within a tissue. Here, we present an cell spreading assay on E-cadherin-coated glass or polydimethylsiloxane (PDMS) substrates for detailed microscopy-based analysis cadherin adhesions. We describe steps preparation coverslips and PDMS gels, E-cadherin coating, spreading. Epithelial can be seeded surfaces, thereby mimicking AJ formation in X-Y dimension, making it...