1. B-cell-specific conditional expression of Myd88p.L252P leads to the development of diffuse large B-cell lymphoma in mice.

    Blood 127(22):2732 (2016) PMID 27048211 PMCID PMC4891954

    The adaptor protein MYD88 is critical for relaying activation of Toll-like receptor signaling to NF-κB activation. MYD88 mutations, particularly the p.L265P mutation, have been described in numerous distinct B-cell malignancies, including diffuse large B-cell lymphoma (DLBCL). Twenty-nine percen...
  2. Concepts of Chronic Lymphocytic Leukemia Pathogenesis: DNA Damage Response and Tumor Microenvironment.

    Oncology research and treatment 39(1-2):9 (2016) PMID 26889681

    Pathogenesis of chronic lymphocytic leukemia (CLL) is characterized by specific genetic aberrations and alterations of cellular signaling pathways. In particular, a disturbed DNA damage response (DDR) and an activated B-cell receptor signaling pathway play a major role in promoting CLL cell surv...
  3. 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...
  4. Editorial: Cancer-Associated Defects in the DNA Damage Response: Drivers for Malignant Transformation and Potential Therapeutic Targets.

    Frontiers in Genetics 6:355 (2015) PMID 26734064 PMCID PMC4686599

  5. 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...
  6. 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...
  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. 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...
  10. 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...
  11. 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...
  12. 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...
  13. AATF/Che-1 acts as a phosphorylation-dependent molecular modulator to repress p53-driven apoptosis.

    EMBO Journal 31(20):3961 (2012) PMID 22909821 PMCID PMC3474921

    Following genotoxic stress, cells activate a complex signalling network to arrest the cell cycle and initiate DNA repair or apoptosis. The tumour suppressor p53 lies at the heart of this DNA damage response. However, it remains incompletely understood, which signalling molecules dictate the choi...
  14. The p53 network: cellular and systemic DNA damage responses in aging and cancer.

    Trends in Genetics 28(3):128 (2012) PMID 22265392 PMCID PMC4120491

    Genome instability contributes to cancer development and accelerates age-related pathologies as evidenced by a variety of congenital cancer susceptibility and progeroid syndromes that are caused by defects in genome maintenance mechanisms. DNA damage response (DDR) pathways that are mediated thr...
  15. Posttranscriptional regulation of gene expression-adding another layer of complexity to the DNA damage response.

    Frontiers in Genetics 3:159 (2012) PMID 22936947 PMCID PMC3427493

    In response to DNA damage, cells activate a complex, kinase-based signaling network to arrest the cell cycle and allow time for DNA repair, or, if the extend of damage is beyond repair capacity, induce apoptosis. This signaling network, which is collectively referred to as the DNA damage respons...
  16. The BAR domain protein PICK1 regulates cell recognition and morphogenesis by interacting with Neph proteins.

    Molecular and Cellular Biology 31(16):3241 (2011) PMID 21690291 PMCID PMC3147803

    Neph proteins are evolutionarily conserved membrane proteins of the immunoglobulin superfamily that control the formation of specific intercellular contacts. Cell recognition through these proteins is essential in diverse cellular contexts such as patterning of the compound eye in Drosophila mel...
  17. NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway.

    Journal of Cell Biology 193(4):633 (2011) PMID 21555462 PMCID PMC3166863

    The conserved Hippo signaling pathway regulates organ size in Drosophila melanogaster and mammals and has an essential role in tumor suppression and the control of cell proliferation. Recent studies identified activators of Hippo signaling, but antagonists of the pathway have remained largely el...
  18. Is post-transcriptional stabilization, splicing and translation of selective mRNAs a key to the DNA damage response?

    Cell Cycle 10(1):23 (2011) PMID 21173571 PMCID PMC3048069

    In response to DNA damage, cells activate a complex, kinase-based signaling network that consist of two components--a rapid phosphorylation-driven signaling cascade that results in immediate inhibition of Cdk/cyclin complexes to arrest the cell cycle along with recruitment of repair machinery to...
  19. DNA damage activates a spatially distinct late cytoplasmic cell-cycle checkpoint network controlled by MK2-mediated RNA stabilization.

    Molecular Cell 40(1):34 (2010) PMID 20932473 PMCID PMC3030122

    Following genotoxic stress, cells activate a complex kinase-based signaling network to arrest the cell cycle and initiate DNA repair. p53-defective tumor cells rewire their checkpoint response and become dependent on the p38/MK2 pathway for survival after DNA damage, despite a functional ATR-Chk...
  20. A mitotic phosphorylation feedback network connects Cdk1, Plk1, 53BP1, and Chk2 to inactivate the G(2)/M DNA damage checkpoint.

    PLoS Biology 8(1):e1000287 (2010) PMID 20126263 PMCID PMC2811157

    DNA damage checkpoints arrest cell cycle progression to facilitate DNA repair. The ability to survive genotoxic insults depends not only on the initiation of cell cycle checkpoints but also on checkpoint maintenance. While activation of DNA damage checkpoints has been studied extensively, molecu...