A5062595582- Cancer Genomics and Diagnostics
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Chromosomal and Genetic Variations
- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- Artificial Intelligence in Healthcare
- Cancer-related Molecular Pathways
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Genomic variations and chromosomal abnormalities
- Single-cell and spatial transcriptomics
- Molecular Biology Techniques and Applications
- Polyamine Metabolism and Applications
- 14-3-3 protein interactions
- Healthcare Systems and Public Health
- Genomics and Phylogenetic Studies
- Wnt/β-catenin signaling in development and cancer
- Genetic factors in colorectal cancer
- Fungal and yeast genetics research
- Cellular transport and secretion
- Prenatal Screening and Diagnostics
- Bioinformatics and Genomic Networks
- Amino Acid Enzymes and Metabolism
BioMed X Institute
2019-2024
Merck (Germany)
2023
European Molecular Biology Laboratory
2015-2022
European Molecular Biology Laboratory
2016-2021
DKFZ-ZMBH Alliance
2010-2014
Heidelberg University
2010-2014
Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma genes have not been defined and screening guidelines for genetic counselling testing paediatric patients are available. We aimed to assess define these provide evidence future guidelines.
A remarkable observation emerging from recent cancer genome analyses is the identification of chromothripsis as a one-off genomic catastrophe, resulting in massive somatic DNA structural rearrangements (SRs). Largely due to lack suitable model systems, mechanistic basis has remained elusive. We developed an integrative method termed "complex alterations after selection and transformation (CAST)," enabling efficient vitro generation complex including chromothripsis, using cell perturbations...
Chromosome instability (CIN) is associated with poor survival and therapeutic outcome in a number of malignancies. Despite this correlation, CIN can also lead to growth disadvantages. Here, we show that simultaneous overexpression the mitotic checkpoint protein Mad2 Kras(G12D) or Her2 mammary glands adult mice results overactivation delay tumor onset. Time-lapse imaging organotypic cultures pathologic analysis prior establishment reveals error-prone mitosis, arrest, cell death. Nonetheless,...
Chromosome loss that results in monosomy is detrimental to viability, yet it frequently observed cancers. How cancers survive with unknown. Using p53-deficient monosomic cell lines, we find chromosome impairs proliferation and genomic stability. Transcriptome proteome analysis demonstrates reduced expression of genes encoded on the monosomes, which partially compensated some cases. Monosomy also induces global changes gene expression. Pathway enrichment reveals involved ribosome biogenesis...
Patterns of gene expression in tumors can arise as a consequence or result genomic instability, characterized by the accumulation somatic copy number alterations (SCNAs) and point mutations (PMs). Expression signatures have been widely used markers for both SCNAs PMs could be thought to associate with distinct given their different formation mechanisms. Here we test this notion systematically investigating SCNA, PM, transcriptome data from 2660 cancer patients representing 11 tumor types....
Abstract Double-strand breaks (DSBs) are the most toxic type of DNA lesions. Cells repair these lesions using either end protection- or resection-coupled mechanisms. To study DSB choice, we present C olor A ssay T racing- R epair (CAT-R) to simultaneously quantify via protection and resection pathways. CAT-R introduces DSBs CRISPR/Cas9 in a tandem fluorescent reporter, whose distinguishes small insertions/deletions from large deletions. We demonstrate applications chemical genetic screens....
Congenital gliobastoma multiforme (GBM) is rare and little known about the molecular defects underlying initiation progression of this tumor type. We present a case congenital GBM analyzed by conventional cytogenetics, fluorescence in situ hybridization, array comparative genomic hybridization next generation sequencing. On cytogenetic analysis we detected reciprocal translocation t(6;12)(q21;q24.3). By sequencing, was shown to form fusion between 5' region ZCCHC8 3' ROS1. RT-PCR analyses...
TP53 deficiency is the most common alteration in cancer; however, this alone typically insufficient to drive tumorigenesis. To identify genes promoting tumorigenesis combination with deficiency, we perform genome-wide CRISPR-Cas9 knockout screens coupled proliferation and transformation assays isogenic cell lines. Loss of several known tumor suppressors enhances cellular transformation. neddylation pathway promotes uncontrolled exclusively TP53-deficient cells. Combined loss CUL3 activates...
The occurrence and formation of genomic structural variants (SVs) is known to be influenced by the 3D chromatin architecture, but extent magnitude have been challenging study. Here, we apply Hi-C study organization before after induction chromothripsis in human cells. We use manually assemble derivative chromosomes following massive complex rearrangements, which allows us sources SV their consequences on gene regulation. observe an action–reaction interplay whereby architecture directly...
High-risk human papillomavirus (hrHPV) types induce immortalization of primary epithelial cells. Previously we demonstrated that foreskin keratinocytes (HFKs) is HPV type dependent, as reflected by the presence or absence a crisis period before reaching immortality. This study determined how capacity ten hrHPV relates to DNA damage induction and overall genomic instability in HFKs.Twenty five cell cultures obtained transduction (i.e. HPV16/18/31/33/35/45/51/59/66/70 E6E7) two three HFK...
Synthetic lethality describes a genetic interaction between two perturbations, leading to cell death, whereas neither event alone has significant effect on viability. This concept can be exploited specifically target tumor cells. CRISPR viability screens have been widely employed identify cancer vulnerabilities. However, an approach systematically infer interactions from is missing.Here we describe PAn-canceR Inferred lethalities (PARIS), machine learning PARIS predicts synthetic lethal (SL)...
Abstract Chromosome loss that results in monosomy is detrimental to viability, yet, it frequently observed cancers. How cancers survive with unknown. Using p53 deficient monosomic cell lines, we found chromosome impairs proliferation and genomic stability. Transcriptome proteome analysis revealed a partial compensation of the gene dosage changes mitigates effects loss. Monosomy triggers global expression differ from trisomy. We show ribosome biogenesis translation were commonly downregulated...
// Francesca R. Dejure 1 , Joachim Butzer Ralph K. Lindemann 2 and Balca Mardin BioMed X Institute (GmbH), Heidelberg, Germany Translational Innovation Platform Oncology, Merck KGaA, Darmstadt, Correspondence to: Mardin, email: mardin@bio.mx Keywords: SLC6A14; metabolic stress; transcriptional regulation; methionine; AMPK Received: May 09, 2020     Accepted: September 10, Published: December 01, 2020 Copyright: © et al. This is an open access article distributed...
To ensure genomic integrity, living organisms have evolved diverse molecular processes for sensing and repairing damaged DNA. If improperly repaired, DNA damage can give rise to different types of mutations, an important class which are structural variants (SVs). In spite their importance phenotypic variation genome evolution, potential contributors SV formation in Saccharomyces cerevisiae (budding yeast), a highly tractable model organism, not fully recognized. Here, we developed applied...
Abstract An important goal in cancer research is to identify driver genes and mutations. Reasoning that such mutations often alter enzymatic functions, we investigated the role of enzyme families. Using pan-cancer genomic data established mutation catalogues, found an unexpectedly high rate helicases, making helicases most frequently mutated family cancer. Based on both functional perturbation screens analyses, provide evidence cancers with converge increased instability faulty DNA repair....
Abstract The occurrence and formation of genomic structural variants (SV) is known to be influenced by the 3D chromatin architecture, but extent magnitude has been challenging study. Here, we apply Hi-C study organization before after induction chromothripsis in human cells. We use manually assemble derivative chromosomes following massive complex rearrangements, which allowed us sources SV their consequences on gene regulation. observe an action-reaction interplay whereby architecture...