The main goal the Genomic Instability Group is to understand the molecular mechanisms underlying cancer and other age-associated diseases, with the ultimate objective of translating this knowledge into effective treatments for patients. To this end, we have developed over the years several molecular tools and in vivo models, which have led us to make important progress in basic as well as in translational research. Among other achievements, we have extensively studied the molecular mechanisms by which cells duplicate and repair their genomes, developed new inhibitors that can be used for targeted cancer therapy, and created mouse models that revealed the physiological consequences of genomic instability. More recently, we have developed an interest in exploring the mechanisms of drug resistance in cancer therapy and how to overcome this problem in cancer, as well as in other age-related diseases lacking a cure, such as neurodegeneration.
Investigadores
- Vanesa Lafarga
- Matilde Murga
Becarios Post-doctorales
- Ivó Hernández
Becarios Pre-Doctorales
- Gema López
- Jorge Mota
- Belén Navarro
- Anabel Sáez
- Pablo Valledor
Técnicos de Laboratorio
- Marta Elena Antón
- Alicia González
- Sara Rodrigo
Publicaciones
- (2023). A Multiparametric and High-Throughput Platform for Host-Virus Binding Screens. Nano Lett (in press). Publicación CNIO.
- (2023). PD-L1ATTAC mice reveal the potential of depleting PD-L1 expressing cells in cancer therapy. Aging (Albany NY) 15, 1791-1807. Publicación CNIO.
- (2023). A chemical screen underscores the essential role of STAT1-dependent IFN? signaling to regulate HLA-I expression in cancer cells. MicroPubl Biol (in press). Publicación CNIO.
- (2022). Distinct roles for PARP-1 and PARP-2 in c-Myc-driven B-cell lymphoma in mice.. Blood 139, 228-239. Publicación CNIO.
- (2022). A bispecific monomeric nanobody induces spike trimer dimers and neutralizes SARS-CoV-2 in vivo. Nat Commun 13, 155. Publicación CNIO.
Open Access
- (2022). Targeting the nucleolus as a therapeutic strategy in human disease. Trends Biochem Sci (in press). Publicación CNIO.
- (2022). Activation of the integrated stress response is a vulnerability for multidrug-resistant FBXW7-deficient cells. EMBO Mol Med 0, e15855. Publicación CNIO.
- (2022). Prolonged estrogen deprivation triggers a broad immunosuppressive phenotype in breast cancer cells. Mol Oncol 16, 148-165. Publicación CNIO.
Open Access
- (2022). Emerging concepts in drug discovery for cancer therapy. Mol Oncol 16, 3757-3760. Publicación CNIO.
- (2022). Alkylating Agent-Induced Toxicity and Melatonin-Based Therapies. Front Pharmacol 13, 873197. Publicación CNIO.
- (2022). An in silico analysis identifies drugs potentially modulating the cytokine storm triggered by SARS-CoV-2 infection.. Sci Rep 12, 1626. Publicación CNIO.
Open Access
- (2022). New regulators of the tetracycline-inducible gene expression system identified by chemical and genetic screens. FEBS Open Bio 12, 1896-1908. Publicación CNIO.
- (2021). USP7 limits CDK1 activity throughout the cell cycle. EMBO J 40, e99692. Publicación CNIO.
- (2021). Widespread displacement of DNA- and RNA-binding factors underlies toxicity of arginine-rich cell-penetrating peptides. EMBO J 40, e99692. Publicación CNIO.
- (2021). USP7 and VCP FAF1 define the SUMO/Ubiquitin landscape at the DNA replication fork. Cell Reports 37, 109819. Publicación CNIO.
- (2021). A chemical screen for modulators of mRNA translation identifies a distinct mechanism of toxicity for sphingosine kinase inhibitors. PLoS Biol 19, e3001263. Publicación CNIO.
- (2021). Coordinating DNA Replication and Mitosis through Ubiquitin/SUMO and CDK1.. Int J Mol Sci 22, 8796. Publicación CNIO.
- (2020). ATR expands embryonic stem cell fate potential in response to replication stress. Elife 12, e54756. Publicación CNIO.
Open Access
- (2020). GRK2-Dependent HuR Phosphorylation Regulates HIF1a Activation Under Hypoxia or Adrenergic Stress. Cancers 12, E1216. Publicación CNIO.
Open Access
- (2020). Supraphysiological protection from replication stress does not extend mammalian lifespan.. Aging (Albany NY) 12, 5612-5624. Publicación CNIO.
- (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. Publicación CNIO.
- (2020). PDS5 proteins are required for proper cohesin dynamics and participate in replication fork protection. J Biol Chem 295, 146-157. Publicación CNIO.
Open Access
- (2019). TIAR controls mitotic entry, maintains genome stability and retains CDK1 in checkpoint bodies.. EMBO Rep 20, pii: e46224. Publicación CNIO.
- (2019). BRCA1 Haploinsufficiency Is Masked by RNF168-Mediated Chromatin Ubiquitylation. Mol Cell 73, 1267-1281. Publicación CNIO.
- (2019). A Chemical Screen Identifies Compounds Capable of Selecting for Haploidy in Mammalian Cells.. Cell Reports 28, 597-604. Publicación CNIO.
Open Access
- (2019). A Chemical Screen Identifies Compounds Limiting the Toxicity of C9ORF72 Dipeptide Repeats. Cell Chem Biol 26, 235-243. Publicación CNIO.
- (2019). TIAR marks nuclear G2/M transition granules and restricts CDK1 activity under replication stress. EMBO Rep 20, e46224. Publicación CNIO.
- (2019). Nucleolin reorganization and nucleolar stress in purkinje cells of mutant PCD mice. Neurobiol Dis 127, 312-322. Publicación CNIO.
- (2018). Targeting ATR in cancer. Nat Rev Cancer 18, 586-595. Publicación CNIO.
- (2018). ATR is required to complete meiotic recombination in mice. Nat Commun 9, 2622. Publicación CNIO.
Open Access
- (2018). ERF deletion rescues RAS deficiency in mouse embryonic stem cells. Genes Dev 32, 568-576. Publicación CNIO.
Open Access
- (2018). CBP-mediated SMN acetylation modulates Cajal body biogenesis and the cytoplasmic targeting of SMN. Cell Mol Life Sci 75, 527-576. Publicación CNIO.
- (2018). The RNA Polymerase II Factor RPAP1 Is Critical for Mediator-Driven Transcription and Cell Identity. Cell Reports 22, 396-410. Publicación CNIO.
Open Access
- (2018). USP7 couples DNA replication termination to mitotic entry. bioRxiv (in press). Publicación CNIO.
- (2018). DNA and RNA binding mediate the toxicity of arginine-rich peptides encoded by C9ORF72 GGGGCC repeats. bioRxiv (in press). Publicación CNIO.