A5057155809- Cancer-related Molecular Pathways
- DNA Repair Mechanisms
- Microtubule and mitosis dynamics
- Chemical Synthesis and Analysis
- Ubiquitin and proteasome pathways
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Bacterial biofilms and quorum sensing
- Bacterial Genetics and Biotechnology
- RNA Research and Splicing
- Bacteriophages and microbial interactions
- Antibiotic Resistance in Bacteria
Saarland University
2022-2025
Helmholtz Institute for Pharmaceutical Research Saarland
2022-2025
Helmholtz Centre for Infection Research
2022-2025
Medizinische Hochschule Hannover
2023
The RNA-binding protein IGF2BP2/IMP2/VICKZ2/p62 is overexpressed in several tumor entities, promotes tumorigenesis and progression, has been suggested to worsen the disease outcome. aim of this study (I) validate IMP2 as a potential target for colorectal cancer, (II) set up screening assay small-molecule inhibitors IMP2, (III) test biological activity obtained hit compounds. Analyses liver cancer gene expression data showed reduced survival patients with high higher advanced tumors. In vitro...
Chromosomal instability (CIN) drives tumor heterogeneity, complicating cancer therapy. Although Polo-like kinase 1 (PLK1) overexpression induces CIN, direct inhibition of PLK1 has shown limited clinical benefits. We therefore performed a genome-wide synthetic dosage lethality (SDL) screen to identify effective alternative targets and validated over 100 candidates using in vivo vitro secondary CRISPR screens. employed direct-capture Perturb-seq assess the transcriptional consequences...
Small macrocyclic peptides are promising candidates for new anti-infective drugs. To date, such have been poorly studied in the context of anti-virulence targets. Using phage display and a self-designed peptide library, we identified cyclic heptapeptide that can bind carbon storage regulator A (CsrA) from Yersinia pseudotuberculosis displace bound RNA. This disulfide-bridged peptide, showed an IC50 value low micromolar range. Upon further characterization, cyclisation was found to be...
Summary Tumor heterogeneity poses a significant challenge in combating treatment resistance. Despite Polo-like kinase 1 (PLK1) being universally overexpressed cancers and contributing to chromosomal instability (CIN), direct PLK1 inhibition hasn’t yielded clinical progress. To address this, we utilized the synthetic dosage lethality (SDL) approach, targeting PLK1’s genetic interactions for selective killing of tumor cells while mitigating heterogeneity-associated challenges. Employing...
Abstract Polymicrobial infections involving various combinations of microorganisms, such as Escherichia , Pseudomonas or Yersinia can lead to acute and chronic diseases in for example the gastrointestinal respiratory tracts. Our aim is modulate microbial communities by targeting posttranscriptional regulator system called carbon storage A (CsrA) (or also repressor secondary metabolites (RsmA)). In previous studies, we identified easily accessible CsrA binding scaffolds macrocyclic peptides...