A5048207756- Cellular Mechanics and Interactions
- Force Microscopy Techniques and Applications
- Cell Adhesion Molecules Research
- Lipid Membrane Structure and Behavior
- Advanced Fluorescence Microscopy Techniques
- Cancer Immunotherapy and Biomarkers
- Analytical Chemistry and Sensors
- Cancer, Lipids, and Metabolism
- Retinal Development and Disorders
- Phosphodiesterase function and regulation
- Cancer, Hypoxia, and Metabolism
- Receptor Mechanisms and Signaling
- Lipid metabolism and biosynthesis
- RNA modifications and cancer
- Cell Image Analysis Techniques
- Caveolin-1 and cellular processes
- Ovarian cancer diagnosis and treatment
- Luminescence and Fluorescent Materials
- Cancer Cells and Metastasis
- Mitochondrial Function and Pathology
- Photoreceptor and optogenetics research
- Signaling Pathways in Disease
- ATP Synthase and ATPases Research
- Skin and Cellular Biology Research
- Advanced Electron Microscopy Techniques and Applications
The Netherlands Cancer Institute
2019-2025
Oncode Institute
2021-2025
Dutch Cancer Society
2021-2024
Leiden University
2012-2022
Huygens Institute for History and Culture of the Netherlands
2015-2022
Czech Academy of Sciences, Institute of Physics
2015
University of Twente
2014
The combination of micropillar array technology to measure cellular traction forces with super-resolution imaging allowed us obtain force maps and simultaneously zoom in on individual focal adhesions single-molecule accuracy. We achieved a detection precision 500 pN mean localization 30 nm. Key the achievement was two-step etching process that provided an integrated spacer next permitted stable reproducible observation cells micropillars within short working distance high-magnification, high...
Red-to-blue triplet–triplet annihilation upconversion was obtained in giant unilamellar vesicles.
Aggregation of α-synuclein has been linked to both familial and sporadic Parkinson's disease. Recent studies suggest that aggregates may spread from cell raise questions about the propagation neurodegeneration. While continuous progress made characterizing in vitro, there is a lack information regarding structure these species inside cells. Here, we use confocal fluorescence microscopy combination with direct stochastic optical reconstruction microscopy, dSTORM, investigate uptake when added...
While immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, their efficacy in high-grade serous ovarian (HGSOC) remains limited. Some patients, however, achieve lasting responses, emphasizing the need to understand how tumor microenvironment and molecular characteristics influence ICI response. The phase 2 Neo-Pembro study (NCT03126812) included 33 untreated stage IV HGSOC who were scheduled for 6 cycles of carboplatin-paclitaxel interval cytoreductive surgery....
Tetraspanin CD151 has been suggested to regulate cell adhesion through its association with laminin-binding integrins α3β1 and α6β4; however, precise function in keratinocyte remains elusive. In this study, we investigated the role of formation maintenance laminin-associated adhesions. We show that CD151, binding integrin α3β1, plays a critical stabilization an structure distinct molecular composition hemidesmosomes tetraspanin features. These hybrid cell-matrix adhesions, which are formed...
Homologous recombination (HR) is a DNA repair process that requires homologous sequence for the of double-stranded breaks. The search homology rate limiting step HR, but dynamics in vivo are currently poorly understood. This largely due to lack tools visualize action living human cells. Here, we show RAD51 and MND1, two proteins operating search, become visible long filamentous structures several hours after break formation. Using GFP-MND1 can these filaments cells find they highly dynamic,...
Fluorescence Lifetime Imaging (FLIM) is an intrinsically quantitative method to screen for protein-protein interactions and frequently used record the outcome of signal transduction events. With new highly sensitive photon efficient FLIM instrumentation, technique also becomes attractive screen, with high temporal resolution, fast changes in Förster Resonance Energy Transfer (FRET), such as those occurring upon activation cell signaling. The second messenger cyclic adenosine monophosphate...
In cell-matrix adhesions, integrin receptors and associated proteins provide a dynamic coupling of the extracellular matrix (ECM) to cytoskeleton. This allows bidirectional transmission forces between ECM cytoskeleton, which tunes intracellular signaling cascades that control survival, proliferation, differentiation, motility. The quantitative relationships recruitment distinct adhesion local cellular traction are not known. Here, we applied super-resolution microscopy adhesions formed on...
In estrogen-receptor-positive, HER2-negative (ER+HER2-) breast cancer, higher levels of tumor infiltrating lymphocytes (TILs) are often associated with a poor prognosis and this phenomenon is still poorly understood. Fibroblasts represent one the most frequent cells in cancer harbor immunomodulatory capabilities. Here, we evaluate molecular clinical impact spatial patterns TILs fibroblast ER+HER2- cancer. We used deep neural network to locate identify tumor, TILs, fibroblasts on hematoxylin...
Single-molecule imaging of proteins in a 2D environment like membranes has been frequently used to extract diffusive properties multiple fractions receptors. In 3D the apparent however change with observation time due movements molecules out depth-of-field microscope. Here we developed mathematical framework that allowed us correct for fraction size limited detection volume single-molecule imaging. We applied our findings on mobility activated glucocorticoid receptors cell nucleus, and found...
<h3>Background</h3> An increasing body of evidence suggests that in addition to the type, density, and state immune cells tumor microenvironment (TME), also their proximity cancer influences immunotherapy outcome. For example, favorable responses checkpoint inhibitors melanoma are associated with higher densities CD8<sup>+</sup> tumor-infiltrating lymphocytes (TIL) within 20 μm distance cells. This notion is line understanding upon specific antigen recognition, cytotoxic T physically engage...
Abstract This abstract is being presented as a short talk in the scientific program. A full printed Proffered Abstracts section (PR009) of Conference Program/Proceedings. Citation Format: Tim Arnoldus, Alex van Vliet, Adriaan F.H. de Groot, Niek Blomberg, Onno B. Bleijerveld, Susan E. Hal-van Veen, Anita Grootemaat, Rolf Harkes, Nicole N. der Wel, Maarten Altelaar, Martin Giera, Daniel S. Peeper. Cytidine diphosphate diacylglycerol synthase 2 synthetic lethal target mesenchymal cancers...
Abstract Synthetic lethal interactions (SLIs) can provide a therapeutic index, as illustrated by PARP inhibition of BRCA-deficient cancers. This clinical success, and other examples, have spurred efforts to identify additional cancer-associated SLIs. Whereas SLIs based on genomic alterations in cancer been identified, we set out explore the SLI space function differential RNA expression profiles normal tissue, covering all ∼3.4e8 gene pairs. In our bioinformatic pipeline, synthetic lethality...
Window studies are gaining traction to assess (molecular) changes in short timeframes. Decreased tumor cell positivity for the proliferation marker Ki67 is often used as a proxy treatment response. Immunohistochemistry (IHC)-based on tissue from neo-adjuvant trials was previously reported be predictive long-term response endocrine therapy breast cancer postmenopausal women, but none of these enrolled premenopausal women. Nonetheless, being this subpopulation. We compared pathologist assessed...
ABSTRACT In cell matrix adhesions, integrin receptors and associated proteins provide a dynamic coupling of the extracellular (ECM) to cytoskeleton. This allows bidirectional transmission forces between ECM cytoskeleton, which tunes intracellular signaling cascades that control survival, proliferation, differentiation, motility. The quantitative relationships recruitment distinct adhesion local cellular traction are not known. Here, we applied superresolution microscopy adhesions formed on...