A5060411509- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Cancer-related gene regulation
- Microtubule and mitosis dynamics
- Cancer, Hypoxia, and Metabolism
- MicroRNA in disease regulation
- Protein Degradation and Inhibitors
- Cancer Cells and Metastasis
- Hippo pathway signaling and YAP/TAZ
- Axon Guidance and Neuronal Signaling
- RNA modifications and cancer
- Metabolomics and Mass Spectrometry Studies
- Ubiquitin and proteasome pathways
- 3D Printing in Biomedical Research
- Cell Image Analysis Techniques
- Cancer-related Molecular Pathways
- RNA Research and Splicing
- Cancer, Lipids, and Metabolism
- Developmental Biology and Gene Regulation
- Computational Drug Discovery Methods
- Genomics and Chromatin Dynamics
- Plant Surface Properties and Treatments
- RNA Interference and Gene Delivery
- Endoplasmic Reticulum Stress and Disease
- Peroxisome Proliferator-Activated Receptors
Nuvisan (Germany)
2021-2025
Bayer (Germany)
2014-2024
ETH Zurich
2009-2015
Max Planck Institute for Biophysical Chemistry
2004-2009
École Polytechnique Fédérale de Lausanne
2009
Max Planck Society
2004
University of Göttingen
2000-2002
Cancer cells in poorly vascularized tumor regions need to adapt an unfavorable metabolic microenvironment. As distance from supplying blood vessels increases, oxygen and nutrient concentrations decrease cancer react by stopping cell cycle progression becoming dormant. cytostatic drugs mainly target proliferating cells, dormancy is considered as a major resistance mechanism this class of anti-cancer drugs. Therefore, substances that have the potential enhance cytostatic-based chemotherapy...
Abstract Spheroids are three-dimensional cellular models with widespread basic and translational application across academia industry. However, methodological transparency guidelines for spheroid research have not yet been established. The MISpheroID Consortium developed a crowdsourcing knowledgebase that assembles the experimental parameters of 3,058 published spheroid-related experiments. Interrogation this identified heterogeneity in setup spheroids. Empirical evaluation interlaboratory...
Cul3 (Cullin3)-based E3 ubiquitin ligases recently emerged as critical regulators of mitosis. In this study, we identify two mammalian BTB (Bric-a-brac–Tramtrack–Broad complex)-Kelch proteins, KLHL21 and KLHL22, that interact with are required for efficient chromosome alignment. Interestingly, but not KLHL22 is necessary cytokinesis regulates translocation the chromosomal passenger complex (CPC) from chromosomes to spindle midzone in anaphase, similar previously described BTB-Kelch proteins...
The use of lipid nanoparticles (LNPs) for therapeutic RNA delivery has gained significant interest, particularly highlighted by recent milestones such as the approval Onpattro and two mRNA-based SARS-CoV-2 vaccines. However, despite substantial advancements in this field, our understanding structure internal organization RNA-LNPs -and their relationship to efficacy, both vitro vivo- remains limited. In study, we present a coarse-grained molecular dynamics (MD) approach that allows...
Abstract Multiple myeloma is a plasma cell malignancy characterized by marked heterogeneous genomic instability including frequent genetic alterations in epigenetic enzymes. In particular, the histone methyltransferase Enhancer of Zeste Homolog 2 (EZH2) overexpressed multiple myeloma. EZH2 catalytic component polycomb repressive complex (PRC2), master transcriptional regulator differentiation. catalyzes methylation lysine 27 on H3 and its deregulation cancer has been reported to contribute...
Structural mutants of p53 induce global protein destabilization and misfolding, followed by aggregation. First evidence indicates that can be part condensates aggregation potentially transitions through a condensate-like state. We show states fluorescently labeled structural mutant in the nucleus living cancer cells. furthermore identified small molecule compounds interact with lead to dissolution condensates. The same condensation tagged DNA-binding mutant, indicating differentially alter...
Abstract Owing to lagging or insufficient neo-angiogenesis, hypoxia is a feature of most solid tumors. Hypoxic tumor regions contribute resistance against antiproliferative chemotherapeutics, radiotherapy and immunotherapy. Targeting cells in hypoxic areas therefore an important strategy for cancer treatment. Most approaches targeting focus on the inhibition adaption pathways but only limited number compounds with potential specifically target have been identified. By using spheroids...
Abstract Cancer stem cells (CSCs) are involved in metastasis and resistance development, thus affecting anticancer therapy efficacy. The underlying pathways required for CSC maintenance survival not fully understood only a limited number of treatment strategies to specifically target CSCs have been identified. To identify novel targeting compounds, we here set-up an aldehyde dehydrogenase (ALDH)-based phenotypic screening system that allows automated standardized identification CSCs. By...
Abstract Due to its frequent mutations in multiple lethal cancers, KRAS is one of the most‐studied anticancer targets nowadays. Since discovery druggable allosteric binding site containing a G12C mutation, has been focus attention oncology research. We report here computationally driven approach aimed at identifying novel and selective covalent inhibitors. The workflow involved initial enumeration virtual molecules tailored for site. Tools such as pharmacophore modeling, docking, free‐energy...
The application of three-dimensional (3D) cell cultures such as spheroids and organoids is growing in popularity both academia industry. However, morphology the 3D architecture remains remarkably understudied. Here, we introduce an open-access Spheroid Light Microscopy Image Atlas (SLiMIA) that can serve a training set for studies cultures. We provide images with variety metadata: 9 microscopes, 47 lines, 8 culture media, 4 spheroid formation methods multiple seeding densities; totalling...
Emotions coordinate our behavior and physiological states during survival-salient events pleasurable interactions. Even though we are often consciously aware of current emotional state, such as anger or happiness, the mechanisms giving ...Emotions felt in body, somatosensory feedback has been proposed to trigger conscious experiences. Here reveal maps bodily sensations associated with different emotions using a unique topographical self-report method. In ...
Syndecan (Sdc) is a conserved transmembrane heparan sulfate proteoglycan (HSPG) bearing additional chondroitin (CS) modifications on its extracellular domain. In vertebrates, this domain of Sdc shed and acts as soluble effector cellular communication events, cytoplasmic participates in intracellular signaling needed to maintain epithelial integrity. Drosophila, has been shown be necessary for Slit signaling-dependent axon myotube guidance during CNS development muscle pattern formation. We...
RUVBL1 (RuvB-like1) and RUVBL2 (RuvB-like 2) are integral components of multisubunit protein complexes involved in processes ranging from cellular metabolism, transcription chromatin remodeling to DNA repair. Here, we show that although known form heterodimeric which they stabilize each other, the subunits separate during cytokinesis. In anaphase-to-telophase transition, localizes structures mitotic spindle apparatus, where it partially co-localizes with polo-like kinase 1 (PLK1). The...
Proteolysis triggered by the anaphase-promoting complex (APC) is needed for sister chromatid separation and exit from mitosis. APC a ubiquitin ligase whose activity tightly controlled during cell cycle. To identify factors involved in regulation of APC-mediated proteolysis, Saccharomyces cerevisiae GAL-cDNA library was screened genes overexpression prevented degradation an target protein, mitotic cyclin Clb2. Genes encoding G 1 , S, cyclins were identified, consistent with previous data...
Ubiquitin-dependent proteolysis of specific target proteins is required for several important steps during the cell cycle. Degradation such strictly cycle-regulated and triggered by two large ubiquitin ligases, termed anaphase-promoting complex (APC) Skp1/Cullin/F-box (SCF). Here we show that yeast Ran-binding protein 1 (Yrb1p), a predominantly cytoplasmic implicated in nucleocytoplasmic transport, cycle regulated degradation. Depletion Yrb1p results accumulation unbudded G1cells cells...
Traditionally, small molecule-based drug discovery has mainly focused on proteins as the target. Opening RNA an additional target space for molecules offers possibility to therapeutically modulate disease-driving non-coding targets well mRNA of otherwise undruggable protein targets. MALAT1 is a highly conserved long-noncoding whose overexpression correlates with poor overall patient survival in some cancers. We report here fluorescence in-situ hybridization-based high-content imaging screen...
Abstract YAP1/TAZ have been shown to be aberrantly activated oncogenes in several human solid tumors, resulting enhanced cell proliferation, metastasis and provision of a pro-tumorigenic microenvironment, making targets for novel cancer therapies. Yet, the development effective inhibitors these potent has challenging. In this work, we break new ground direction through identification activity. This study describes target deconvolution small molecule oncogenic activity with anti-tumor vivo. A...