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December 2012 - present
Humboldt-Universität zu Berlin
- Raf-1 profiling
- Development of a characteristic gene regulatory proﬁle of Raf-1 activation with help of model-based inference strategies.
November 2010 - November 2012
Humboldt-Universität zu Berlin
- Investigations on the optimization of the in vitro culture of Eimeria falciformis
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...
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, as patients regularly relapse with reactivation of the targeted pathways. We identify the nuclear protein SFPQ to be synthetically l...
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...
Oncogenic mutations in KRAS or BRAF are frequent in colorectal cancer and activate the ERK kinase. Here, we find graded ERK phosphorylation correlating with cell differentiation in patient-derived colorectal cancer organoids with and without KRAS mutations. Using reporters, single cell transcriptomics and mass cytometry, we observe cell type-specif...
Der RAF-MEK-ERK-Signalweg steuert grundlegende, oftmals entgegengesetzte zelluläre Prozesse wie die Proliferation und Apoptose von Zellen. Die Dauer des vermittelten Signals wurde als entscheidener Faktor für die Steuerung dieser Prozesse identifiziert. Es ist jedoch nicht eindeutig geklärt, wie die verschiedenen früh und spät reagierenden Genexpre...
Mutations activating the KRAS GTPase or the BRAF kinase are frequent in colorectal cancer. Here, we use inducible transgenic expression of KRASG12V or BRAFV600E in intestinal organoids of mice to investigate oncogenic signal transduction in the mitogen-activated protein kinase (MAPK) cascade with cellular resolution. Using phospho-protein, reporter...
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...
The RAF-MEK-ERK cascade is one of the most studied signaling pathways as it controls many vital cellular programs. There has been an immense amount of effort to determine ERK target proteins that are involved in regulating these programs. Classical biochemical and genetic approaches have identified hundreds of direct ERK substrates, and with the ad...
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...