A5043339503- CRISPR and Genetic Engineering
- Neuroblastoma Research and Treatments
- Advanced Breast Cancer Therapies
- Genetics, Bioinformatics, and Biomedical Research
- Cancer therapeutics and mechanisms
- Epigenetics and DNA Methylation
- Science, Research, and Medicine
- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
- RNA Interference and Gene Delivery
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Genomics and Phylogenetic Studies
- Spectroscopy and Chemometric Analyses
- Cancer Diagnosis and Treatment
- Medical Imaging and Pathology Studies
- Computational Drug Discovery Methods
- Spectroscopy Techniques in Biomedical and Chemical Research
- Lung Cancer Treatments and Mutations
- Single-cell and spatial transcriptomics
- Multiple and Secondary Primary Cancers
- Medical and Biological Ozone Research
- Microtubule and mitosis dynamics
- Renal cell carcinoma treatment
- Pancreatic and Hepatic Oncology Research
Max Delbrück Center
2022-2024
Charité - Universitätsmedizin Berlin
2023-2024
Comprehensive Cancer Center Erlangen
2024
Humboldt-Universität zu Berlin
2023
Freie Universität Berlin
2023
Friedrich-Alexander-Universität Erlangen-Nürnberg
2023
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2022
University of York
2020
Heidelberg University
2017-2020
University Hospital Heidelberg
2020
Abstract Extrachromosomal DNAs (ecDNAs) are common in cancer, but many questions about their origin, structural dynamics and impact on intratumor heterogeneity still unresolved. Here we describe single-cell extrachromosomal circular DNA transcriptome sequencing (scEC&T-seq), a method for parallel of full-length mRNA from single cells. By applying scEC&T-seq to cancer cells, intercellular differences ecDNA content while investigating transcriptional impact. Oncogene-containing ecDNAs...
Abstract Genomic instability arising from defective responses to DNA damage 1 or mitotic chromosomal imbalances 2 can lead the sequestration of in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark ageing and diseases associated with genomic instability, catalogue genetic players that regulate generation remains be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases ( n = 71) decreases 74) formation,...
The chromosomal theory of inheritance dictates that genes on the same chromosome segregate together while different chromosomes assort independently
DNA amplifications in cancer do not only harbor oncogenes. We sought to determine whether passenger coamplifications could create collateral therapeutic vulnerabilities. Through an analysis of >3,000 genomes followed by the interrogation CRISPR-Cas9 loss-of-function screens across >700 cell lines, we determined that are accompanied distinct dependency profiles. In a proof-of-principle study, demonstrate coamplification bona fide gene DEAD-Box Helicase 1 (DDX1) creates increased on mTOR...
Circular extrachromosomal DNA (ecDNA) is a form of oncogene amplification found across cancer types and associated with poor outcome in patients. ecDNA can be structurally complex contain rearranged sequences derived from multiple chromosome locations. As the structure impact regulation may indicate mechanisms its formation, disentangling it at high resolution sequencing data essential. Even though methods have been developed to identify reconstruct genome sequencing, remains challenging...
We introduce an advanced and flexible spectral focusing coherent anti-Stokes Raman scattering (CARS) microspectroscopy scheme based on the independent control of pump, Stokes, probe frequencies offered by a pulse shaper. Adjusting instantaneous bandwidth 10 fs pulses in focus microscope to different linewidths assures high resolution signal intensities from CH-bond fingerprint region. Experimental results are confirmed simulations CARS generation process. By delaying probe, increased...
Abstract Neuroblastoma is characterised by extensive inter- and intra-tumour genetic heterogeneity varying clinical outcomes. One possible driver for this are extrachromosomal DNAs (ecDNA), which segregate independently to the daughter cells during cell division can lead rapid amplification of oncogenes. While ecDNA-mediated oncogene has been shown be associated with poor prognosis in many cancer entities, effects ecDNA copy number on intermediate phenotypes still poorly understood. Here, we...
Abstract Circular extrachromosomal DNA (ecDNA) is a form of oncogene amplification found across cancer types and associated with poor outcome in patients. EcDNA can be structurally complex contain rearranged sequences derived from multiple chromosome locations. As the structure ecDNA impact regulation may indicate mechanisms its formation, disentangling it at high resolution sequencing data essential. Even though methods have been developed to identify reconstruct genome sequencing, remains...
Eslicarbazepine acetate (ESL) is a dibenzazepine anticonvulsant approved as adjunctive treatment for partial-onset epileptic seizures. Following first pass hydrolysis of ESL, S-licarbazepine (S-Lic) represents around 95% circulating active metabolites. S-Lic the main enantiomer responsible activity and this proposed to be through blockade voltage-gated Na+ channels (VGSCs). ESL both have voltage-dependent inhibitory effect on current in N1E-115 neuroblastoma cells expressing neuronal VGSC...
Abstract The small-molecule inhibitor of ataxia telangiectasia and Rad3-related protein (ATR), elimusertib, is currently being tested clinically in various cancer entities adults children. Its preclinical antitumor activity pediatric malignancies, however, largely unknown. We here assessed the elimusertib 38 cell lines 32 patient-derived xenograft (PDX) models derived from common solid tumor entities. Detailed vitro vivo molecular characterization treated enabled evaluation response...
ABSTRACT The chromosomal theory of inheritance has dominated human genetics, including cancer genetics. Genes on the same chromosome segregate together while genes different chromosomes assort independently, providing a fundamental tenet Mendelian inheritance. Extrachromosomal DNA (ecDNA) is frequent event in that drives oncogene amplification, dysregulated gene expression and intratumoral heterogeneity, through random segregation during cell division. Distinct ecDNA sequences, herein termed...
<p>Overview of the systematic approach to identify collateral lethal dependencies associated with passenger gene coamplifications in cancers.</p>
<p>Overview of the systematic approach to identify collateral lethal dependencies associated with passenger gene coamplifications in cancers.</p>