1. A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer.

    Cell 162(1):146 (2015) PMID 26140595

    KRAS is one of the most frequently mutated oncogenes in human cancer. Despite substantial efforts, no clinically applicable strategy has yet been developed to effectively treat KRAS-mutant tumors. Here, we perform a cell-line-based screen and identify strong synergistic interactions between cell...
  2. Label-Free Protein-RNA Interactome Analysis Identifies Khsrp Signaling Downstream of the p38/Mk2 Kinase Complex as a Critical Modulator of Cell Cycle Progression.

    PLoS ONE 10(5):e0125745 (2015) PMID 25993413 PMCID PMC4439058

    Growing evidence suggests a key role for RNA binding proteins (RBPs) in genome stability programs. Additionally, recent developments in RNA sequencing technologies, as well as mass-spectrometry techniques, have greatly expanded our knowledge on protein-RNA interactions. We here use full transcri...
  3. Molecular pathways: exploiting tumor-specific molecular defects in DNA repair pathways for precision cancer therapy.

    Clinical Cancer Research 20(23):5882 (2014) PMID 25451105

    Disabling mutations in genome maintenance and DNA repair pathways are frequently observed in cancer. These DNA repair defects represent genetic aberrations that are specific to cancer cells and not present in healthy tissues. It is thought that these molecular defects produce a "mutator phenotyp...
  4. Molecular pathways: exploiting tumor-specific molecular defects in DNA repair pathways for precision cancer therapy.

    Clinical Cancer Research 20(23):5882 (2014) PMID 25451105

    Disabling mutations in genome maintenance and DNA repair pathways are frequently observed in cancer. These DNA repair defects represent genetic aberrations that are specific to cancer cells and not present in healthy tissues. It is thought that these molecular defects produce a "mutator phenotyp...
  5. Molecular pathways: exploiting tumor-specific molecular defects in DNA repair pathways for precision cancer therapy.

    Clinical Cancer Research 20(23):5882 (2014) PMID 25451105

    Disabling mutations in genome maintenance and DNA repair pathways are frequently observed in cancer. These DNA repair defects represent genetic aberrations that are specific to cancer cells and not present in healthy tissues. It is thought that these molecular defects produce a "mutator phenotyp...
  6. Cancer-specific defects in DNA repair pathways as targets for personalized therapeutic approaches.

    Trends in Genetics 30(8):326 (2014) PMID 25017190

    Defects in DNA repair pathways enable cancer cells to accumulate genomic alterations that contribute to their aggressive phenotype. However, tumors rely on residual DNA repair capacities to survive the damage induced by genotoxic stress. This dichotomy might explain why only isolated DNA repair ...
  7. Cancer-specific defects in DNA repair pathways as targets for personalized therapeutic approaches.

    Trends in Genetics 30(8):326 (2014) PMID 25017190

    Defects in DNA repair pathways enable cancer cells to accumulate genomic alterations that contribute to their aggressive phenotype. However, tumors rely on residual DNA repair capacities to survive the damage induced by genotoxic stress. This dichotomy might explain why only isolated DNA repair ...
  8. A functional cancer genomics screen identifies a druggable synthetic lethal interaction between MSH3 and PRKDC.

    Cancer Discovery 4(5):592 (2014) PMID 24556366

    Here, we use a large-scale cell line-based approach to identify cancer cell-specific mutations that are associated with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) dependence. For this purpose, we profiled the mutational landscape across 1,319 cancer-associated genes of 67 distinct...
  9. A functional cancer genomics screen identifies a druggable synthetic lethal interaction between MSH3 and PRKDC.

    Cancer Discovery 4(5):592 (2014) PMID 24556366

    Here, we use a large-scale cell line-based approach to identify cancer cell-specific mutations that are associated with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) dependence. For this purpose, we profiled the mutational landscape across 1,319 cancer-associated genes of 67 distinct...
  10. Cancer-specific defects in DNA repair pathways as targets for personalized therapeutic approaches

    Trends in Genetics (2014)

    • Tumor cells display entity-specific signatures of DNA repair pathway alterations • HR defects are associated with DSB-PK- and PARP1-dependence ...
  11. Cell-autonomous and non-cell-autonomous mechanisms of transformation by amplified FGFR1 in lung cancer.

    Cancer Discovery 4(2):246 (2014) PMID 24302556

    The 8p12 locus (containing the FGFR1 tyrosine kinase gene) is frequently amplified in squamous cell lung cancer. However, it is currently unknown which of the 8p12-amplified tumors are also sensitive to fibroblast growth factor receptor (FGFR) inhibition. We found that, in contrast with other re...
  12. Cell-autonomous and non-cell-autonomous mechanisms of transformation by amplified FGFR1 in lung cancer.

    Cancer Discovery 4(2):246 (2014) PMID 24302556

    The 8p12 locus (containing the FGFR1 tyrosine kinase gene) is frequently amplified in squamous cell lung cancer. However, it is currently unknown which of the 8p12-amplified tumors are also sensitive to fibroblast growth factor receptor (FGFR) inhibition. We found that, in contrast with other re...
  13. A reversible gene-targeting strategy identifies synthetic lethal interactions between MK2 and p53 in the DNA damage response in vivo.

    Cell Reports 5(4):868 (2013) PMID 24239348 PMCID PMC3962842

    A fundamental limitation in devising new therapeutic strategies for killing cancer cells with DNA damaging agents is the need to identify synthetic lethal interactions between tumor-specific mutations and components of the DNA damage response (DDR) in vivo. The stress-activated p38 mitogen-activ...
  14. Phospho-Ser/Thr-binding domains: navigating the cell cycle and DNA damage response.

    Nature Reviews: Molecular Cell Biology 14(9):563 (2013) PMID 23969844

    Coordinated progression through the cell cycle is a complex challenge for eukaryotic cells. Following genotoxic stress, diverse molecular signals must be integrated to establish checkpoints specific for each cell cycle stage, allowing time for various types of DNA repair. Phospho-Ser/Thr-binding...
  15. Phospho-Ser/Thr-binding domains: navigating the cell cycle and DNA damage response.

    Nature Reviews: Molecular Cell Biology 14(9):563 (2013) PMID 23969844

    Coordinated progression through the cell cycle is a complex challenge for eukaryotic cells. Following genotoxic stress, diverse molecular signals must be integrated to establish checkpoints specific for each cell cycle stage, allowing time for various types of DNA repair. Phospho-Ser/Thr-binding...
  16. Cancer-specific defects in DNA repair pathways as targets for personalized therapeutic approaches

    Trends in Genetics (2013)

    • Tumor cells display entity-specific signatures of DNA repair pathway alterations. • HR defects are associated with DNA-PK- and PARP1-dependence. ...
  17. Cancer-specific defects in DNA repair pathways as targets for personalized therapeutic approaches

    Trends in Genetics (2013)

    • Tumor cells display entity-specific signatures of DNA repair pathway alterations. • HR defects are associated with DNA-PK- and PARP1-dependence. ...
  18. Cancer-specific defects in DNA repair pathways as targets for personalized therapeutic approaches

    Trends in Genetics (2013)

    • Tumor cells display entity-specific signatures of DNA repair pathway alterations. • HR defects are associated with DNA-PK- and PARP1-dependence. ...
  19. The ciliopathy disease protein NPHP9 promotes nuclear delivery and activation of the oncogenic transcriptional regulator TAZ.

    Human Molecular Genetics 21(26):5528 (2012) PMID 23026745

    Nephronophthisis (NPH) is a genetically heterogenous kidney disease and represents the most common genetic cause for end-stage renal disease in children. It is caused by the mutation of genes encoding for the nephrocystin proteins (NPHPs) which localize to primary cilia or centrosomes, classifyi...
  20. The ciliopathy disease protein NPHP9 promotes nuclear delivery and activation of the oncogenic transcriptional regulator TAZ.

    Human Molecular Genetics 21(26):5528 (2012) PMID 23026745

    Nephronophthisis (NPH) is a genetically heterogenous kidney disease and represents the most common genetic cause for end-stage renal disease in children. It is caused by the mutation of genes encoding for the nephrocystin proteins (NPHPs) which localize to primary cilia or centrosomes, classifyi...