A5028257499- Cancer Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Advanced Electron Microscopy Techniques and Applications
- Cellular transport and secretion
- Ubiquitin and proteasome pathways
- Extracellular vesicles in disease
- Advanced biosensing and bioanalysis techniques
- Cell Adhesion Molecules Research
- Photosynthetic Processes and Mechanisms
- Advanced Fluorescence Microscopy Techniques
- RNA Research and Splicing
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Ferroptosis and cancer prognosis
- Antimicrobial Peptides and Activities
- Immune Response and Inflammation
- Bacteriophages and microbial interactions
- Pancreatic function and diabetes
- Natural product bioactivities and synthesis
- Inflammatory mediators and NSAID effects
- Cardiomyopathy and Myosin Studies
- Muscle Physiology and Disorders
Leiden University Medical Center
2015-2025
Leiden University
2024
Electron (Ukraine)
2015
The Netherlands Cancer Institute
2001-2011
Instituto Nacional de Metrologia, Qualidade e Tecnologia
2011
Tokyo Medical and Dental University
2007
Netherlands Heart Institute
2007
Harvard University
2007
University of Sheffield
2007
University of Cologne
2007
Extracellular matrix proteins, such as laminins, and endothelial cells are known to influence cardiomyocyte performance; however, the underlying molecular mechanisms remain poorly understood.We used a forward genetic screen in zebrafish identify novel genes required for myocardial function were able lost-contact (loc) mutant, which encodes nonsense mutation integrin-linked kinase (ilk) gene. This loc/ilk mutant is associated with severe defect cardiomyocytes that leads dysfunction....
Noninvasive imaging of differences between the molecular properties cancer and normal tissue has potential to enhance detection tumors. Because overexpression endogenous transferrin receptor (TfR) been qualitatively described for various cancers is presumably due malignant transformation cells, TfR may represent a suitable target application technologies increase smaller In work reported here, investigation into biology this using electron microscopy demonstrated that iron oxide particles...
Loss of pancreatic islet β-cell mass and dysfunction are central in the development type 2 diabetes (T2DM). We recently showed that mature human insulin-containing β-cells can convert into glucagon-containing α-cells ex vivo. This loss identity was characterized by presence transcription factors (Nkx6.1, Pdx1) glucagon+ cells. Here, we investigated whether also occurs vivo, it is related to (pre)diabetes humans nonhuman primates. observed an eight times increased frequency insulin+ cells...
Abstract Purpose: Therapies directed to specific molecular targets are still unmet for patients with triple-negative breast cancer (TNBC). Deubiquitinases (DUB) emerging drug targets. The identification of highly active DUBs in TNBC may lead novel therapies. Experimental Design: Using DUB activity probes, we profiled global activities 52 cell lines and patients' tumor tissues. To validate our findings vivo, employed both zebrafish murine xenograft models. Cellular mechanisms were elucidated...
Whether coat proteins play a widespread role in endocytic recycling remains unclear. We find that ACAP1, GTPase-activating protein (GAP) for ADP-ribosylation factor (ARF) 6, is part of novel clathrin complex regulated by ARF6 two key physiological settings, stimulation-dependent integrin critical cell migration and insulin-stimulated glucose transporter type 4 (Glut4), which required homeostasis. These findings not only advance basic understanding an early mechanistic step but also shed...
Abstract The endosomal system is a highly dynamic multifunctional organelle, whose complexity regulated in part by reversible ubiquitylation. Despite the wide-ranging influence of ubiquitin processes, relatively few enzymes utilizing have been described to control endosome integrity and function. Here we reveal deubiquitylating enzyme (DUB) ubiquitin-specific protease 32 (USP32) as powerful player this context. Loss USP32 inhibits late (LE) transport recycling LE cargos, resulting dispersion...
Synthetic antimicrobial and antibiofilm peptide (SAAP-148) commits significant activities against resistant (AMR) planktonic bacteria biofilms. However, SAAP-148 is limited by its low selectivity index, i.e., ratio between cytotoxicity activity, as well bioavailability at infection sites. We hypothesized that formulation of in PLGA nanoparticles (SAAP-148 NPs) improves the index due to sustained local release peptide. The aim this study was investigate physical functional characteristics NPs...
<title>Abstract</title> Disease-associated RNA binding protein (RBP) aggregation is a hallmark of several age-related neurodegenerative diseases. How insoluble RBP aggregates leads to cellular dysfunction poorly understood. Here, we investigated the molecular mechanisms affected by PABPN1 aggregates. are nuclear, but regulates nuclear export mRNA. To explore consequences aggregates, performed sequencing and proteomic studies in subcellular fractions an inducible human muscle cell model....
<title>Abstract</title> The accumulation of intracellular protein aggregates is a hallmark aging. In hereditary adult-onset neuromuscular diseases (NMDs), these are not only characteristic but also pathogenic, marking age-related disorders. transition from age-associated non-pathogenic to disease-driving pathogenic remains poorly understood. Poly(A) binding nuclear 1 (PABPN1) forms in post-mitotic aged cells. However, short trinucleotide expansion PABPN1 leads muscle dysfunction...
This unit describes subcellular localization of proteins/antigens using high-resolution cryo-immunogold electron microscopy, which allows study topological biochemistry at the ultrastructural level. is most sensitive procedure for immunodetection antigens on ultrathin sections prepared from chemically fixed cells or tissues, because aldehyde fixation only denaturation step. The omission harsh organic solvents (such as those used plastic embedding) ensures better preservation protein...
The correlative light-electron microscopy is reported showing the labels in their ultrastructural context.
Proteotoxic stress causes profound endoplasmic reticulum (ER) membrane remodeling into a perinuclear quality control compartment (ERQC) for the degradation of misfolded proteins. Subsequent return to homeostasis involves clearance ERQC by endolysosomes. However, factors that ER integrity and dynamics remain unclear. Here, we identify vimentin intermediate filaments as anchors We show engage ER-embedded RING finger protein 26 (RNF26) at C-terminus its domain. This restricts RNF26 subdomains...
Summary We have recently reported electron tomographic studies of sections obtained from chemically fixed E. coli cells overproducing the 60‐kDa chemotaxis receptor Tsr. Membrane extracts these prepared in presence Tween‐80 display hexagonally close‐packed microcrystalline assemblies Tsr, with a repeating unit large enough to accommodate six Tsr molecules arranged as trimers dimers. Here, we report direct visualization clusters (i) vitrified cell suspensions by rapid plunge‐freezing, and...
Abstract Many drug delivery systems end up in the lysosome because they are built from covalent or kinetically inert supramolecular bonds. To reach other organelles, nanoparticles hence need to either be made a labile interaction that allows re‐assembly of inside cell following endocytic uptake, or, taken by mechanism short‐circuits classical endocytosis pathway. In this work, intracellular fate nanorods self‐assemble via Pt…Pt cyclometalated platinum(II) compounds, is studied. These...
Electron tomography is a powerful method for determining the three-dimensional structures of large macromolecular assemblies, such as cells, organelles, and multiprotein complexes, when crystallographic averaging methods are not applicable. Here we used electron tomographic imaging to determine molecular architecture Escherichia coli cells engineered overproduce bacterial chemotaxis receptor Tsr. Tomograms constructed from fixed, cryosectioned revealed that overproduction Tsr led formation...