The Genomic Instability Laboratory is interested in understanding the molecular mechanisms causing cancer and other age-related diseases, in order to provide the knowledge needed to develop novel treatments for these diseases. Initially, we focused on the study of replicative stress, a type of DNA damage that fuels genomic instability and is present in many types of cancer. Those studies led to important contributions to basic research and also led to the development of potent and selective ATR inhibitors that were transferred to the pharmaceutical industry for clinical development. Subsequent to elucidating the mechanisms of resistance to ATR inhibition by genetic screens, our Group gradually developed an interest in understanding how cancer cells develop resistance to therapies, and how we can target therapy-resistant cancer cells. In addition, we are actively involved in exploring the contribution of nucleolar stress to cancer and neurodegeneration.
Investigadores Científicos
- Vanesa Lafarga
- Matilde Murga
Becarios Post-doctorales
- Ivó Hernández
Becarios Pre-Doctorales
- Amin El Manchoud
- Gema López
- Mario López
- Jorge Mota
- Belén Navarro
- Anabel Sáez
Técnicos de Laboratorio
- Marta Elena Antón
- Alicia González
- Sara Rodrigo
Publicaciones
- (2024). Nucleolar stress caused by arginine-rich peptides triggers a ribosomopathy and accelerates aging in mice. Mol Cell 84, 1527-1540. Publicación CNIO.
- (2024). Discovery of a novel inhibitor of macropinocytosis with antiviral activity. Mol Ther 32, 3012-3024. Publicación CNIO.
- (2024). The anti-leprosy drug clofazimine reduces polyQ toxicity through activation of PPARγ. EBioMedicine 103, 105124. Publicación CNIO.
- (2024). Cyclophilin D plays a critical role in the survival of senescent cells. EMBO J 43, 5972-6000. Publicación CNIO.
- (2024). SETD8 inhibition targets cancer cells with increased rates of ribosome biogenesis. Cell Death Dis 15, 694. Publicación CNIO.
Open Access - (2024). GRK2-mediated AKT activation controls cell cycle progression and G2 checkpoint in a p53-dependent manner. Cell Death Dis 10, 385. Publicación CNIO.
- (2023). Actionable cancer vulnerability due to translational arrest, p53 aggregation and ribosome biogenesis stress evoked by the disulfiram metabolite CuET. Cell Death Differ 30, 1666-1678. Publicación CNIO. Open Access
- (2023). Decoding protein methylation function with thermal stability analysis.. Nat Commun 14, 3016. Publicación CNIO. Open Access
- (2023). A Multiparametric and High-Throughput Platform for Host-Virus Binding Screens. Nano Lett 23, 3701-3707. 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. Open Access
- (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. Open Access
- (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. Open Access
- (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. Open Access
- (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