- Cancer Cells and Metastasis
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Cellular Mechanics and Interactions
- Hippo pathway signaling and YAP/TAZ
- Cancer Genomics and Diagnostics
- Cell Adhesion Molecules Research
- Genital Health and Disease
- Single-cell and spatial transcriptomics
- Cancer Mechanisms and Therapy
- Cancer Research and Treatments
- Extracellular vesicles in disease
- Advanced Fluorescence Microscopy Techniques
- 3D Printing in Biomedical Research
- Microtubule and mitosis dynamics
- Nanoplatforms for cancer theranostics
- Cancer, Hypoxia, and Metabolism
- Genetic factors in colorectal cancer
- Glioma Diagnosis and Treatment
- Biomarkers in Disease Mechanisms
- Prostate Cancer Treatment and Research
- Phagocytosis and Immune Regulation
- bioluminescence and chemiluminescence research
- Cell Image Analysis Techniques
- MicroRNA in disease regulation
The Netherlands Cancer Institute
2006-2024
Oncode Institute
2007-2024
University Medical Center Utrecht
2010-2024
Royal Netherlands Academy of Arts and Sciences
2008-2024
Dutch Cancer Society
2018-2024
Roche (Switzerland)
2024
Princess Máxima Center
2024
Amsterdam University Medical Centers
2023
Washington University in St. Louis
2020
Hubrecht Institute for Developmental Biology and Stem Cell Research
2010-2019
Most cancer cells release heterogeneous populations of extracellular vesicles (EVs) containing proteins, lipids, and nucleic acids. In vitro experiments showed that EV uptake can lead to transfer functional mRNA altered cellular behavior. However, similar in vivo remain challenging because take up EVs cannot be discriminated from non-EV-receiving cells. Here, we used the Cre-LoxP system directly identify tumor vivo. We show released by malignant are taken less located within same distant...
Invadopodia are matrix-degrading membrane protrusions in invasive carcinoma cells. The mechanisms regulating invadopodium assembly and maturation not understood. We have dissected the stages of show that invadopodia use cortactin phosphorylation as a master switch during these processes. In particular, was found to regulate cofilin Arp2/3 complex–dependent actin polymerization. Cortactin directly binds inhibits its severing activity. is required release this inhibition so can sever filaments...
Exosomes are small endosome-derived extracellular vesicles implicated in cell–cell communication and secreted by living cells when multivesicular bodies (MVBs) fuse with the plasma membrane (PM). Current techniques to study exosome physiology based on isolation procedures after secretion, precluding direct dynamic insight into mechanics of biogenesis regulation their release. In this study, we propose real-time visualization MVB–PM fusion overcome these limitations. We designed...
Epithelial-mesenchymal transition (EMT) is a transient, reversible process of cell de-differentiation where cancer cells transit between various stages an EMT continuum, including epithelial, partial EMT, and mesenchymal states. We have employed Tamoxifen-inducible dual recombinase lineage tracing systems combined with live imaging 5-cell RNA sequencing to track undergoing or full in the MMTV-PyMT mouse model metastatic breast cancer. In primary tumors, infrequently undergo mostly epithelial...
Significance Stem cells crucially depend on their complex microenvironment, also called niche. The niche is defined as an anatomic site, consisting of specialized cells. These anchor stem and provide the with physical protection essential growth maintenance signals. In murine small intestinal crypts, Paneth constitute important part cellular for Lgr5 + which they are intermingled. molecules such Wnt3, EGF, Notch ligands to maintain cell. There exists no typical cell in colon. Here, we show...
Colorectal cancer stem cells (CSCs) express Lgr5 and display extensive cell-like multipotency self-renewal are thought to seed metastatic disease. Here, we used a mouse model of colorectal (CRC) human tumor xenografts investigate the cell origin metastases. We found that most disseminated CRC in circulation were Lgr5− formed distant metastases which Lgr5+ CSCs appeared. This plasticity occurred independently stemness-inducing microenvironmental factors was indispensable for outgrowth, but...
Recent work has demonstrated that following the clearance of infection a stable population memory T cells remains present in peripheral organs and contributes to control secondary infections. However, little is known about how tissue-resident behave situ they encounter newly infected target cells. Here we demonstrate antigen-specific CD8 + remain skin herpes simplex virus show steady-state crawling behavior between keratinocytes. Spatially explicit simulations migration these indicate...
Significance Metastasis is the main cause of cancer death, but underlying mechanisms are largely unknown. Here, we developed an orthotopic organoid transplantation approach and used engineered human colon tumor organoids to study contribution common CRC mutations metastasis. Using this approach, show that combination oncogenic in Wnt, EGFR, P53, TGF-β signaling pathways facilitates efficient cell migration These allow growth independent stem niche factors, enabling cells grow at foreign...
Next-generation biosensors enable in vivo monitoring of ERK activity and detection RhoA small cellular extensions.
Abstract Extracellular vesicles (EVs) form an endogenous transport system for intercellular transfer of biological cargo, including RNA, that plays a pivotal role in physiological and pathological processes. Unfortunately, whereas effects EV-mediated RNA are abundantly studied, regulatory pathways mechanisms remain poorly defined due to lack suitable readout systems. Here, we describe highly-sensitive CRISPR-Cas9-based reporter allows direct functional study small non-coding molecules at...
Lamellipodial protrusion and directional migration of carcinoma cells towards chemoattractants, such as epidermal growth factor (EGF), depend upon the spatial temporal regulation actin cytoskeleton by actin-binding proteins (ABPs). It is generally hypothesized that activity many ABPs are temporally spatially regulated PIP2; however, this mainly based on in vitro–binding structural studies, vivo evidence lacking. Here, we provide first data directly visualize cofilin PIP2 living cells. We...
An abdominal imaging window allows in vivo visualization of dynamic cellular processes, including liver metastasis and islet cell transplantation.