A5016671863- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- Ocular Oncology and Treatments
- Retinal Development and Disorders
- CRISPR and Genetic Engineering
- Prenatal Screening and Diagnostics
- Pluripotent Stem Cells Research
- Neuroblastoma Research and Treatments
- Cancer-related Molecular Pathways
- interferon and immune responses
- Molecular Biology Techniques and Applications
- Microtubule and mitosis dynamics
- COVID-19 Clinical Research Studies
- Metabolism and Genetic Disorders
- Cancer Genomics and Diagnostics
- Gene expression and cancer classification
- Mitochondrial Function and Pathology
- SARS-CoV-2 and COVID-19 Research
- Single-cell and spatial transcriptomics
- Genomics and Rare Diseases
- Wnt/β-catenin signaling in development and cancer
- Retinal Diseases and Treatments
- Genomics and Chromatin Dynamics
- Cancer Immunotherapy and Biomarkers
- SARS-CoV-2 detection and testing
Leibniz Institute DSMZ – German Collection of Microorganisms and Cell Cultures
2020-2025
Technische Universität Braunschweig
2024
University of Duisburg-Essen
2013-2022
Essen University Hospital
2014-2018
Heinrich Heine University Düsseldorf
2011
Vienna Biocenter
2009
CeMM Research Center for Molecular Medicine
2008-2009
Austrian Academy of Sciences
2008-2009
Continuous cell lines are important and commonly used in vitro models breast cancer (BC) research. Selection of the appropriate model line is crucial requires consideration their molecular characteristics. To characterize BC depth, we profiled a panel 29 authenticated publicly available by mRNA-sequencing, mutation analysis, immunoblotting. Gene expression profiles separated two major clusters that represent basal-like (mainly triple-negative BC) luminal subtypes, respectively. HER2-positive...
Abstract Genomic imprinting is an epigenetic phenomenon resulting in parent-of-origin-specific gene expression that regulated by a differentially methylated region. Gene mutations or failures the process lead to development of disorders, such as Angelman syndrome. The symptoms syndrome are caused absence functional UBE3A protein neurons brain. To create human neuronal model for syndrome, we reprogrammed dermal fibroblasts patient carrying defined three-base pair deletion into induced...
Genomic imprinting is an epigenetic process that results in parental-specific gene expression. Advances understanding the mechanism regulates imprinted expression mammals have largely depended on generating targeted manipulations embryonic stem (ES) cells are analysed vivo mice. However, genomic consists of distinct developmental steps, some which occur post-implantation embryos, indicating they could be studied vitro ES cells. The mouse Igf2r shows only stages, when repression paternal...
The SARS-CoV-2 pandemic is a major global threat that sparked research efforts. Pre-clinical and biochemical studies firstly rely on cell culture experiments where the importance of choosing an appropriate model often underestimated. We here present bottom-up approach to identify suitable permissive cancer lines for drug screening virus research. Human were screened cellular entry factors ACE2 TMPRSS2 based RNA-seq data Cancer Cell Line Encyclopedia (CCLE). However, experimentally testing...
Retinoblastoma are childhood eye tumors arising from retinal precursor cells. Two distinct retinoblastoma subtypes with different clinical behavior have been described based on gene expression and methylation profiling. Using consensus clustering of DNA analysis 61 retinoblastomas, we identify a MYCN-driven cluster subtype 2 retinoblastomas characterized by hypomethylation high genes involved in protein synthesis. Subtype outside the mesodermal development, including NKX2-5. Knockdown MYCN...
In retinoblastoma research tumor-derived cell lines remain an important model to investigate tumorigenesis and new therapy options, due limited tumor material lack of adequate animal models. A panel 10 was characterized with respect mutation, methylation expression RB1 MYCN. These established represent the most frequent types inactivation together MYCN amplification status, three classes can be distinguished: RB1mut/MYCNnonA, RB1mut/MYCNA RB1wt/MYCNA. identified in five lines, whereby two...
<ns4:p>Human and animal cell lines serve as model systems in a wide range of life sciences such cancer infection research or drug screening. Reproducible data are highly dependent on authenticated, contaminant-free lines, no better delivered than by the official certified biorepositories. Offering web portal to high-throughput information these will facilitate working with comparing references otherwise dispersed at different sources.</ns4:p><ns4:p> </ns4:p><ns4:p> We here provide...
Retinoblastoma is a tumor of the eye in children under age five caused by biallelic inactivation RB1 suppressor gene maturing retinal cells. Cancer models are essential for understanding development and preclinical research. Because complex organization human retina, such were challenging to develop retinoblastoma. Here, we present an organoid model based on differentiation embryonic stem cells into neural retina after CRISPR/Cas9 mutagenesis. Wildtype heterozygous mutant organoids...
<ns3:p>Human and animal cell lines serve as model systems in a wide range of life sciences such cancer infection research or drug screening. Reproducible data are highly dependent on authenticated, contaminant-free lines, no better delivered than by the official certified biorepositories. Offering web portal to high-throughput information these will facilitate working with comparing references otherwise dispersed at different sources.</ns3:p><ns3:p> </ns3:p><ns3:p> We here provide...
Two isogenic hiPSC lines, ZIPi013-B and ZIPi013-E, were generated by reprogramming fetal dermal fibroblasts with episomal vectors. Previously, the same reprogrammed multiple times in a study comparing other methods. As consequence, genomes have been sequenced times. Both new cell lines offer opportunity to basic stem biology model human disease. They can be applied as reference for creating clones bearing disease mutations on well-characterized genomic background, both demonstrated excellent...
Abstract Structures resembling whole organs, called organoids, are generated using pluripotent stem cells and 3D culturing methods. This relies on the ability of to self‐reorganize after dissociation. In combination with certain supplemented factors, differentiation can be directed toward formation several organ‐like structures. Here, a protocol for generation retinal organoids containing all seven cell types is described. does not depend Matrigel, by keeping single independent at times,...
Retinoblastoma is the most common malignant cancer of eye in children. Although metastatic retinoblastoma rare, cure rates for this advanced disease remain below 50%. High-level polo-like kinase 1 expression retinoblastomas has previously been shown to be correlated with adverse outcome parameters. Polo-like a serine/threonine involved cell cycle regulation at G2/M transition. inhibition demonstrated have anti-tumour effects preclinical models several paediatric tumours. Here, we assessed...
Angelman syndrome (AS) is a neurodevelopmental disorder with leading symptoms of happy demeanor, intellectual disability, ataxia and seizures. AS can be caused by genetic epigenetic aberrations, resulting in the absence functional UBE3A protein brain. an imprinted gene, which is, neurons brain, expressed exclusively from maternal chromosome 15. The generated iPSC line was derived skin fibroblasts patient AS, who, due to imprinting defect, lacked DNA methylation at 15 center, controls...
The human RB1 gene is imprinted due to integration of the PPP1R26P1 pseudogene into intron 2. harbors gametic differentially methylated region gene, CpG85, which in female germ line. paternally unmethylated CpG85 acts as promoter for alternative transcript 2B RB1, interferes with expression full-length cis. In mice, not present Rb1 and imprinted. Assuming that mechanisms responsible genomic imprinting are conserved, we investigated if mouse can be induced by transferring Rb1. We generated...
The human retinoblastoma gene (RB1) is imprinted; the mouse Rb1 not. Imprinted expression of RB1 due to differential methylation a CpG island (CpG85), which located in pseudogene PPP1R26P1 intron 2 RB1. CpG85 serves as promoter for an alternative transcript, expressed from unmethylated paternal allele only and thought suppress full-length transcript cis. contains another (CpG42), biallelically methylated. To determine influence on expression, we generated vitro murine embryonic stem cell...
Retinoblastoma is a childhood cancer of the retina caused by biallelic inactivation tumor suppressor gene RB1. In heritable retinoblastoma, one allele inherited in mutant form via parental germ cells. To study molecular mechanisms two sublines H1 hESCs were generated, carrying knock-out RB1 heterozygous or homozygous state. Exon 3 was targeted and modified nucleotide deletions using CRISPR/Cas9 nuclease system. Based on nearby single polymorphism, modification could be assigned to allele.
Inactivation of the tumor suppressor gene RB1 is causal for development retinoblastoma, a neural retina arising in children under age five. In addition, secondary mutations are found many other types. To investigate retinoblastoma formation vitro, stem cells with inactivated can be differentiated into retina. enable such studies, two sublines hESC line H9 carrying exon 3 heterozygous or homozygous state were generated and characterized. Homozygous mutation led to loss protein expression....