A5065277867- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Single-cell and spatial transcriptomics
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Monoclonal and Polyclonal Antibodies Research
- Ubiquitin and proteasome pathways
- CAR-T cell therapy research
- HER2/EGFR in Cancer Research
- Genomics and Chromatin Dynamics
- Immunotherapy and Immune Responses
- Advanced Fluorescence Microscopy Techniques
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced biosensing and bioanalysis techniques
- Biofuel production and bioconversion
- Cellular transport and secretion
- Plant-Microbe Interactions and Immunity
- Fungal and yeast genetics research
- Lung Cancer Treatments and Mutations
- Polysaccharides and Plant Cell Walls
- Glycosylation and Glycoproteins Research
- Click Chemistry and Applications
- RNA Research and Splicing
- Endoplasmic Reticulum Stress and Disease
Merus (Netherlands)
2021
Radboud Institute for Molecular Life Sciences
2016-2019
Radboud University Nijmegen
2016-2019
Radboud University Medical Center
2016-2019
University Medical Center Utrecht
2010-2018
Utrecht University
2012
Cancer Genomics Centre
2012
Heidelberg University
2010
University Hospital Heidelberg
2010
Environmental stimuli often lead to heterogeneous cellular responses and transcriptional output. We developed single-cell RNA Immunodetection (RAID) allow combined analysis of the transcriptome intracellular (phospho-)proteins from fixed single cells. RAID successfully recapitulated differentiation-state changes at protein mRNA level in human keratinocytes. Furthermore, we show that differentiated keratinocytes retain high phosphorylated FAK levels, a feature associated with stem cells, also...
Pectins are diverse and very complex biomolecules their structure depends on the plant species tissue. It was previously shown that derivatives of pectic polymers oligosaccharides from pectins have positive effects human health. To obtain specific oligosaccharides, highly defined enzymatic mixes required. Filamentous fungi specialized in cell wall degradation some produce a broad range pectinases. They may therefore shed light enzyme needed for partial hydrolysis. The growth profiles 12 four...
Immuno-PCR combines specific antibody-based protein detection with the sensitivity of PCR-based quantification through use antibody-DNA conjugates. The production such conjugates depends on availability quick and efficient conjugation strategies for two biomolecules. Here, we present an approach to produce cleavable conjugates, employing fast kinetics inverse electron-demand Diels-Alder reaction between tetrazine trans-cyclooctene (TCO). Our strategy consists three steps. First, antibodies...
Significance Wnt/β-catenin signaling is crucial for adult homeostasis and stem cell maintenance, its dysregulation strongly associated to cancer. Upon Wnt binding, receptors assemble into large complexes called signalosomes that provide a platform interactions with downstream effector proteins. The assembly regulation of these remains largely elusive. Here, we use internally tagged ligands as tool isolate analyze the composition endogenous receptor complexes. We identify positive regulator...
Wnt/β-catenin signalling controls development and adult tissue homeostasis causes cancer when inappropriately activated. In unstimulated cells, an Axin1-centred multi-protein complex phosphorylates the transcriptional co-activator β-catenin, marking it for degradation. Wnt antagonizes β-catenin proteolysis, leading to its accumulation target gene expression. How stimulation alters size distribution, composition activity of endogenous Axin1 complexes remains poorly understood. Here, we...
Differentiated cells are epigenetically stable, but can be reprogrammed to pluripotency by expression of the OSKM transcription factors. Despite significant effort, relatively little is known about cellular requirements for reprogramming and how they affect properties induced pluripotent stem cells. We have performed high-content screening with small interfering RNAs targeting 300 chromatin-associated factors extracted colony-level quantitative features. This revealed five morphological...
Abstract Cell-based small molecule screening is an effective strategy leading to new medicines. Scientists in the pharmaceutical industry as well academia have made tremendous progress developing both large-scale and smaller-scale assays. However, accessible universal technology for measuring large numbers of molecular cellular phenotypes many samples parallel not available. Here we present immuno-detection by sequencing (ID-seq) that combines antibody-based protein detection DNA-sequencing...
SCF(βTrCP) is the ubiquitin ligase for a wide variety of substrates and functions in many cellular processes. βTrCP, substrate binding factor SCF complex, has two isoforms, produced from different genes, several splice variants. Despite certain level redundancy, knock-out studies show phenotypes indicating preferential isoforms. However, until now functional differences between βTrCP1 2 were not studied at endogenous protein level. We generated isoform-specific antibodies against βTrCP to...
Abstract Cell-based small molecule screening is an effective strategy leading to new medicines. Scientists in the pharmaceutical industry as well academia have made tremendous progress developing both large-scale and smaller-scale assays. However, accessible universal technology for measuring large numbers of molecular cellular phenotypes many samples parallel not available. Here, we present Immuno-Detection by sequencing (ID-seq) that combines antibody-based protein detection DNA-sequencing...
Abstract Environmental stimuli often lead to heterogeneous cellular responses and transcriptional output. We developed single-cell RNA Immunodetection (RAID) allow combined analysis the transcriptome intracellular (phospho-)proteins from fixed single cells. RAID successfully recapitulated differentiation-state changes at protein mRNA level in human keratinocytes. Furthermore, we show that differentiated keratinocytes retain high phosphorylated FAK levels, a feature associated with stem...
Abstract HER2-driven cancers require phosphatidylinositide-3 kinase (PI3K)/Akt signaling through HER3 to promote tumor growth and survival. The HER2/HER3 complex is most active in the presence of heregulin (HRG) upregulation HRG one key resistance mechanisms after TKI treatment. Zenocutuzumab an bispecific antibody that specifically potently blocks HRG-driven heterodimeric complex. has demonstrated clinical activity patients with advanced cancer where pathway [Ref].Zenocutuzumab was...
Abstract Neuregulin 1 (NRG1) fusion proteins are oncogenic drivers in multiple cancer types, including non-small cell lung cancer, pancreas adenocarcinoma, and other solid tumors. NRG1 bind to HER3 signal through HER2/HER3 heterodimers, leading transformation. Zenocutuzumab is an humanized IgG1 bispecific antibody that specifically potently blocks fusion-driven signaling of the heterodimeric complex. binds via its anti-HER2 monovalent Fab arm domain I HER2. Docking zenocutuzumab this...
Abstract Degradation of cytosolic β-catenin by the APC/Axin1 Destruction Complex represents key regulated step Wnt pathway. It is incompletely understood how Axin1 complex exerts its Wnt-regulated function. We have now examined compositional change endogenous in HEK293T cells upon signaling. Our results demonstrate that not only phosphorylation, but also ubiquitination and proteasomal degradation occur within complex. In disagreement with current views, we find neither a disassembly complex,...
SUMMARY Differentiated cells are epigenetically stable, but can be reprogrammed to pluripotency by expression of the OSKM transcription factors. Despite significant effort, relatively little is known about cellular requirements for reprogramming and how they affect properties induced pluripotent stem (iPSC). We have performed high-content screening with siRNAs targeting 300 chromatin-associated used colony features, such as size shape, well strength homogeneity marker gene define five...