Anja Sieber

Anja Sieber
Charité Universitätsmedizin Berlin | Charité · Institute of Pathology

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40
Publications
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818
Citations

Publications

Publications (40)
Article
Full-text available
Resistance against radio(chemo)therapy-induced cell death is a major determinant of oncological treatment failure and remains a perpetual clinical challenge. The underlying mechanisms are manifold and demand for comprehensive, cancer entity- and subtype-specific examination. In the present study, resistance against radiotherapy was systematically a...
Article
Full-text available
Very high risk neuroblastoma is characterised by increased MAPK signalling, and targeting MAPK signalling is a promising therapeutic strategy. We used a deeply characterised panel of neuroblastoma cell lines and found that the sensitivity to MEK inhibitors varied drastically between these cell lines. By generating quantitative perturbation data and...
Article
Full-text available
In colorectal cancer, oncogenic mutations transform a hierarchically organized and homeostatic epithelium into invasive cancer tissue lacking visible organization. We sought to define transcriptional states of colorectal cancer cells and signals controlling their development by performing single-cell transcriptome analysis of tumors and matched non...
Preprint
Full-text available
Very high risk neuroblastoma is characterised by increased MAPK signalling, and targeting MAPK signalling is a promising therapeutic strategy. We used a deeply characterised panel of neuroblastoma cell lines and found that the sensitivity to MEK inhibitors varied drastically between these cell lines. By generating quantitative perturbation data and...
Preprint
Full-text available
Inhibition of aberrated signaling processes using targeting inhibitors is an important treatment strategy in cancer. However, due to network effects and the rapid onset of resistance, single drug treatments are often ineffective and responses short-lived. The use of multi-drug combinations has the potential to overcome these problems, but to avoid...
Article
In colorectal cancer (CRC), the prevalence of NRAS mutations (5–9%) is inferior to that of KRAS mutations (40–50%). NRAS mutations feature lately during tumour progression and drive resistance to anti-EGFR therapy in KRAS wild-type tumours. To elucidate specific functions of NRAS mutations in CRC, we expressed doxycycline-inducible G12D and Q61K mu...
Preprint
Full-text available
In colorectal cancer, oncogenic mutations transform a hierarchically organized and homeostatic epithelium into invasive cancer tissue lacking visible organization. We sought to identify differences in cellular composition between normal colon and colorectal cancer, and to define signals controlling cancer cell development. We used single cell RNA a...
Article
Full-text available
Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC‐NB1, from a bone marrow metastasis from a patient diagnosed with MYCN‐amplified neuroblastoma and performed whole‐exome s...
Article
Full-text available
HRAS, NRAS, and KRAS isoforms are almost identical proteins that are ubiquitously expressed and activate a common set of effectors. In vivo studies have revealed that they are not biologically redundant; however, the isoform specificity of Ras signaling remains poorly understood. Using a novel panel of isogenic SW48 cell lines endogenously expressi...
Article
Full-text available
Motivation Signal-transduction networks are often aberrated in cancer cells, and new anti-cancer drugs that specifically target oncogenes involved in signaling show great clinical promise. However, the effectiveness of such targeted treatments is often hampered by innate or acquired resistance due to feedbacks, crosstalks or network adaptations in...
Article
Full-text available
Motivation: Intracellular signalling is realised by complex signalling networks which are almost impossible to understand without network models, especially if feedbacks are involved. Modular Response Analysis (MRA) is a convenient modelling method to study signalling networks in various contexts. Results: We developed the software package STASN...
Preprint
Full-text available
New anti-cancer drugs that specifically target oncogenes involved in signalling show great clinical promise. However, the effectiveness of such targeted treatments is often hampered by innate or acquired resistance due to feedbacks, crosstalks or network adaptations in response to drug treatment. Addressing this problem requires an understanding of...
Preprint
Full-text available
Motivation Intracellular signalling is realized by complex signalling networks which are almost impossible to understand without network models, especially if feedbacks are involved. Modular Response Analysis (MRA) is a convenient modelling method to study signalling networks in various contexts. Results We developed a derivative of MRA that is su...
Article
Full-text available
Aberrant cell signaling can cause cancer and other diseases and is a focal point of drug research. A common approach is to infer signaling activity of pathways from gene expression. However, mapping gene expression to pathway components disregards the effect of post-translational modifications, and downstream signatures represent very specific expe...
Article
Full-text available
The RAF-MEK-ERK signalling pathway controls fundamental, often opposing cellular processes such as proliferation and apoptosis. Signal duration has been identified to play a decisive role in these cell fate decisions. However, it remains unclear how the different early and late responding gene expression modules can discriminate short and long sign...
Article
Full-text available
The RAF‐MEK‐ERK signalling pathway controls fundamental, often opposing cellular processes such as proliferation and apoptosis. Signal duration has been identified to play a decisive role in these cell fate decisions. However, it remains unclear how the different early and late responding gene expression modules can discriminate short and long sign...
Article
Genomic features are used as biomarkers of sensitivity to kinase inhibitors used widely to treat human cancer, but effective patient stratification based on these principles remains limited in impact. Insofar as kinase inhibitors interfere with signaling dynamics, and, in turn, signaling dynamics affects inhibitor responses, we investigated associa...
Article
Full-text available
Therapies targeting specific molecular processes, in particular kinases, are major strategies to treat cancer. Genomic features are commonly used as biomarkers for drug sensitivity, but our ability to stratify patients based on these features is still limited. As response to kinase inhibitors is a dynamic process affecting largely signal transducti...
Article
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Impedance-based technologies are advancing methods for measuring proliferation of adherent cell cultures non-invasively and in real time. The analysis of the resulting data has so far been hampered by inappropriate computational methods and the lack of systematic data to evaluate the characteristics of the assay. We used a commercially available sy...
Article
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During early development of female mouse embryos, both X chromosomes are transiently active. X gene dosage is then equalized between the sexes through the process of X chromosome inactivation (XCI). Whether the double dose of X-linked genes in females compared with males leads to sex-specific developmental differences has remained unclear. Using em...
Article
Full-text available
The epidermal growth factor receptor (EGFR) signaling network is activated in most solid tumors, and small-molecule drugs targeting this network are increasingly available. However, often only specific combinations of inhibitors are effective. Therefore, the prediction of potent combinatorial treatments is a major challenge in targeted cancer thera...
Article
Full-text available
Protein levels within signal transduction pathways vary strongly from cell to cell. For example, it has been reported that concentrations of the last kinase within the MAPK signalling module, Erk, varies about four-fold between clonal cells under the same conditions. In the present study, we analysed how signalling pathways can still process inform...

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