A5005238604- Colorectal Cancer Treatments and Studies
- Cancer Cells and Metastasis
- Genetic factors in colorectal cancer
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- HER2/EGFR in Cancer Research
- RNA modifications and cancer
- Cancer-related gene regulation
- Advanced Breast Cancer Therapies
- Single-cell and spatial transcriptomics
- Cancer-related Molecular Pathways
- Neuroendocrine Tumor Research Advances
- Monoclonal and Polyclonal Antibodies Research
- Lung Cancer Research Studies
- Digestive system and related health
- Wnt/β-catenin signaling in development and cancer
- Cancer-related molecular mechanisms research
- Cancer Research and Treatments
- Pancreatic and Hepatic Oncology Research
- Melanoma and MAPK Pathways
- DNA Repair Mechanisms
- Cell Image Analysis Techniques
- Molecular Biology Techniques and Applications
- Genomics and Chromatin Dynamics
- Cancer Immunotherapy and Biomarkers
German Cancer Research Center
2018-2024
Heidelberg University
2018-2024
Charité - Universitätsmedizin Berlin
2015-2024
Humboldt-Universität zu Berlin
2020-2024
Freie Universität Berlin
2020-2024
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2019-2024
Orthopädische Universitätsklinik
2023
Max Planck Institute for Molecular Genetics
2007-2014
In-Q-Tel
2012
Max Delbrück Center
2001-2010
Abstract Motivation: DNA enrichment followed by sequencing is a versatile tool in molecular biology, with wide variety of applications including genome-wide analysis epigenetic marks and mechanisms. A common requirement these diverse comparison read coverage between experimental conditions. The amount samples generated for such comparisons ranges from few replicates to hundreds per condition epigenome-wide association studies. Consequently, there an urgent need software that allows fast...
Wound healing of the skin is a crucial regenerative process in adult mammals. We examined wound conditional mutant mice, which c-Met gene that encodes receptor hepatocyte growth factor/scatter factor was mutated epidermis by cre recombinase. c-Met-deficient keratinocytes were unable to contribute reepithelialization wounds. In closure slightly attenuated, but occurred exclusively few (5%) had escaped recombination. This demonstrates selected and amplified residual cells express functional...
Viruses manipulate cellular metabolism and macromolecule recycling processes like autophagy. Dysregulated might lead to excessive inflammatory autoimmune responses as observed in severe long COVID-19 patients. Here we show that SARS-CoV-2 modulates reduces Accordingly, compound-driven induction of autophagy limits propagation. In detail, SARS-CoV-2-infected cells accumulation key metabolites, activation inhibitors (AKT1, SKP2) reduction proteins responsible for initiation (AMPK, TSC2, ULK1),...
Abstract Recent developments in immuno-oncology demonstrate that not only cancer cells, but also the tumor microenvironment can guide precision medicine. A comprehensive and in-depth characterization of is challenging since its cell populations are diverse be important even if scarce. To identify clinically relevant microenvironmental features, we applied single-cell RNA sequencing to ten human lung adenocarcinomas normal control tissues. Our analyses revealed heterogeneous carcinoma...
Abstract Genetic heterogeneity between and within tumours is a major factor determining cancer progression therapy response. Here we examined DNA sequence copy-number in colorectal (CRC) by targeted high-depth sequencing of 100 most frequently altered genes. In 97 samples, with primary matched metastases from 27 patients, observe inter-tumour concordance for coding mutations; contrast, gene copy numbers are highly discordant as validated fluorescent situ hybridization. To further investigate...
Single-cell transcriptional profiling reveals cell heterogeneity and clinically relevant traits in intra-operatively collected patient-derived tissue. So far, single-cell studies have been constrained by the requirement for prospectively fresh or cryopreserved This limitation might be overcome recent technical developments enabling analysis of FFPE
Gene expression profiling of β-catenin, Cripto and Wnt3 mutant mouse embryos has been used to characterise the genetic networks that regulate early embryonic development. We have defined genes whose is regulated by β-catenin during formation anteroposterior axis mesoderm, identified Cripto,which encodes a Nodal co-receptor, as primary target signals both in embryogenesis well colon carcinoma cell lines tissues. also groups Wnt3/β-catenin signalling primitive streak mesoderm formation. Our...
In demyelinating diseases including multiple sclerosis (MS), neural stem cells (NSCs) can replace damaged oligodendrocytes if the local microenvironment supports required differentiation process. Although chitinase-like proteins (CLPs) form part of this microenvironment, their function in process is unknown. Here, we demonstrate that murine Chitinase 3-like-3 (Chi3l3/Ym1), human Chi3L1 and Chit1 induce oligodendrogenesis. mice, Chi3l3 highly expressed subventricular zone, a cell niche adult...
Abstract The human gastric epithelium forms highly organized gland structures with different subtypes of cells. carcinogenic bacterium Helicobacter pylori can attach to cells and subsequently translocate its virulence factor CagA, but the possible host cell tropism H. is currently unknown. Here, we report that preferentially attaches differentiated in pit region units. Single-cell RNA-seq shows organoid-derived monolayers recapitulate region, while organoids capture Using these models, show...
Transcriptional signatures are an indispensible source of correlative information on disease-related molecular alterations a genome-wide level. Numerous candidate genes involved in disease and factors predictive, as well prognostic, value have been deduced from such portraits, e.g. cancer. However, mechanistic insights into the regulatory principles governing global transcriptional changes lagging behind extensive compilations deregulated genes. To identify regulators transcriptome...
Pancreatic neuroendocrine neoplasms (PanNENs) fall into two subclasses: the well-differentiated, low- to high-grade pancreatic tumors (PanNETs), and poorly-differentiated, carcinomas (PanNECs). While recent studies suggest an endocrine descent of PanNETs, origin PanNECs remains unknown.We performed DNA methylation analysis for 57 PanNEN samples found that distinct profiles separated PanNENs major groups, clearly distinguishing from other PanNETs including NETG3. alterations...
Aberrant CpG methylation is a universal epigenetic trait of cancer cell genomes. However, human samples or lines preclude the investigation changes occurring early during tumour development. Here, we have used MeDIP-seq to analyse DNA methylome APCMin adenoma as model for intestinal initiation, and present list more than 13,000 recurring differentially methylated regions (DMRs) characterizing mouse. We show that Polycomb Repressive Complex (PRC) targets are strongly enriched among...
Oncoproteins such as the BRAFV600E kinase endow cancer cells with malignant properties, but they also create unique vulnerabilities. Targeting of BRAFV600E-driven cytoplasmic signaling networks has proved ineffective, patients regularly relapse reactivation targeted pathways. We identify nuclear protein SFPQ to be synthetically lethal in a loss-of-function shRNA screen. depletion decreases proliferation and specifically induces S-phase arrest apoptosis colorectal melanoma cells....
Lung carcinoid tumors, also referred to as pulmonary neuroendocrine tumors or lung carcinoids, are rare neoplasms of the with a more favorable prognosis than other subtypes cancer. Still, some patients suffer from relapsed disease and metastatic spread. Several recent single-cell studies have provided detailed insights into cellular heterogeneity common cancers, such adeno- squamous cell carcinoma. However, characteristics carcinoids on level yet completely unknown. To study composition gene...
Epidemiological data demonstrate that Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) Alpha and Delta are more transmissible, infectious, pathogenic than previous variants. Phenotypic properties VOC remain understudied. Here, we provide an extensive functional study replication cell entry phenotypes assisted by reverse genetics, mutational mapping spike in lentiviral pseudotypes, viral cellular gene expression studies, infectivity stability assays...
Abstract Single‐cell analyses can be confounded by assigning unrelated groups of cells to common developmental trajectories. For instance, cancer and admixed normal epithelial could adopt similar cell states thus complicating their potential. Here, we develop benchmark CCISM (for Cancer Cell Identification using Somatic Mutations) exploit genomic single nucleotide variants for the disambiguation from genomically non‐cancer in single‐cell data. We find that our method others based on gene...