- Vanesa Lafarga
- Matilde Murga
- Elena Fueyo
- Gema López
- Jorge Mota
- Belén Navarro
- Anabel Sáez
- Laura Sánchez
- Oleksandra Sirozh
- Pablo Valledor
- Marta Elena Antón
- Alicia González
- Sara Rodrigo
In the Genomic Instability Group, our main goal is to understand the molecular mechanisms underlying cancer and other age-related diseases, and then use this knowledge for the development of new therapies. To this end, we combine molecular and cellular biology approaches with chemical and genetic screens that allow us to identify cancer cell vulnerabilities and new druggable targets. In parallel, we develop mouse models of disease, which we can later use as platforms for testing new treatments. With all these tools, in recent years, we have made exciting discoveries in several areas, from basic to translational research. We have contributed to the understanding of fundamental aspects of DNA replication, unveiled new mechanisms of resistance to cancer therapies, and developed anticancer drugs that are now in clinical development. Ultimately, our objective is to translate our findings into better treatments for human disease. During 2020 we made significant advances in several areas related to cancer ontogeny and therapy. For instance, we revealed a tumour suppressor role for the RNA-binding protein EWSR1 and made significant advances in the development of chemical inhibitors of the histone methyltransferase SETD8.
- (2021). Long noncoding RNA NIHCOLE promotes ligation efficiency of DNA double-strand breaks in hepatocellular carcinoma.. Cancer Res (in press). CNIO Publication.
- (2021). Widespread displacement of DNA- and RNA-binding factors underlies toxicity of arginine-rich cell-penetrating peptides. EMBO J 40, e99692. CNIO Publication.
- (2021). USP7 limits CDK1 activity throughout the cell cycle. EMBO J 40, e99692. CNIO Publication.
- (2021). A chemical screen for modulators of mRNA translation identifies a distinct mechanism of toxicity for sphingosine kinase inhibitors. PLoS Biol 19, e3001263. CNIO Publication.
- (2020). PDS5 proteins are required for proper cohesin dynamics and participate in replication fork protection. J Biol Chem 295, 146-157. CNIO Publication. Open Access
- (2020). Supraphysiological protection from replication stress does not extend mammalian lifespan.. Aging (Albany NY) 12, 5612-5624. CNIO Publication.
- (2020). GRK2-Dependent HuR Phosphorylation Regulates HIF1a Activation Under Hypoxia or Adrenergic Stress. Cancers 12, E1216. CNIO Publication. Open Access
- (2020). Mislocalization of SMN from the I-band and M-band in human skeletal myofibers in spinal muscular atrophy associates with primary structural alterations of the sarcomere.. Cell Tissue Res 381, 461-478. CNIO Publication.
- (2020). ATR expands embryonic stem cell fate potential in response to replication stress. Elife 12, e54756. CNIO Publication. Open Access
- (2019). A Chemical Screen Identifies Compounds Capable of Selecting for Haploidy in Mammalian Cells.. Cell Reports 28, 597-604. CNIO Publication. Open Access
- (2019). A Chemical Screen Identifies Compounds Limiting the Toxicity of C9ORF72 Dipeptide Repeats. Cell Chem Biol 26, 235-243. CNIO Publication.
- (2019). BRCA1 Haploinsufficiency Is Masked by RNF168-Mediated Chromatin Ubiquitylation. Mol Cell 73, 1267-1281. CNIO Publication.
- (2019). TIAR marks nuclear G2/M transition granules and restricts CDK1 activity under replication stress. EMBO Rep 20, e46224. CNIO Publication.
- (2019). Nucleolin reorganization and nucleolar stress in purkinje cells of mutant PCD mice. Neurobiol Dis 127, 312-322. CNIO Publication.
- (2019). TIAR controls mitotic entry, maintains genome stability and retains CDK1 in checkpoint bodies.. EMBO Rep 20, pii: e46224. CNIO Publication.
- (2018). USP7 couples DNA replication termination to mitotic entry. bioRxiv (in press). CNIO Publication.
- (2018). DNA and RNA binding mediate the toxicity of arginine-rich peptides encoded by C9ORF72 GGGGCC repeats. bioRxiv (in press). CNIO Publication.
- (2018). Targeting ATR in cancer. Nat Rev Cancer 18, 586-595. CNIO Publication.
- (2018). ERF deletion rescues RAS deficiency in mouse embryonic stem cells. Genes Dev 32, 568-576. CNIO Publication. Open Access
- (2018). The RNA Polymerase II Factor RPAP1 Is Critical for Mediator-Driven Transcription and Cell Identity. Cell Reports 22, 396-410. CNIO Publication. Open Access
- (2018). CBP-mediated SMN acetylation modulates Cajal body biogenesis and the cytoplasmic targeting of SMN. Cell Mol Life Sci 75, 527-576. CNIO Publication.
- (2018). ATR is required to complete meiotic recombination in mice. Nat Commun 9, 2622. CNIO Publication. Open Access
- (2017). TrapSeq: An RNA Sequencing-Based Pipeline for the Identification of Gene-Trap Insertions in Mammalian Cells.. J Mol Biol 429, 2780-2789. CNIO Publication.
- (2017). A p53-dependent response limits the viability of mammalian haploid cells.. Proc Natl Acad Sci USA 114, 9367-9372. CNIO Publication.
- (2016). USP7 is a SUMO deubiquitinase essential for DNA replication.. Nat Struct Mol Biol 23, 270-277. CNIO Publication.
- (2016). Replication fork stability confers chemoresistance in BRCA-deficient cells. Nature 535, 382-387. CNIO Publication.
- (2016). POLD3 Is Haploinsufficient for DNA Replication in Mice. Mol Cell 63, 877-883. CNIO Publication.
- (2016). A Genome-wide CRISPR Screen Identifies CDC25A as a Determinant of Sensitivity to ATR Inhibitors. Mol Cell 62, 307-313. CNIO Publication.
- (2016). Targeting the kinase activities of ATR and ATM exhibits antitumoral activity in mouse models of MLL-rearranged AML.. Sci Signal 9, ra91. CNIO Publication.
- (2016). Efficacy of ATR inhibitors as single agents in Ewing sarcoma. Oncotarget 7, 58759-58767. CNIO Publication. Open Access
- (2016). A SUMO and ubiquitin code coordinates protein traffic at replication factories.. Bioessays 38, 1209-1217. CNIO Publication.
- (2016). The (elusive) role of the SMC5/6 complex.. Cell Cycle 15, 775-776. CNIO Publication.