Genomic Instability Group

Óscar Fernández-Capetillo Group Leader
T +34 917328000 (Ext 3480)
ofernandez@cnio.es

Staff Scientists

Vanesa Lafarga
Matilde Murga

Post-Doctoral Fellows

Ivó Hernández

Graduate Students

Gema López
Jorge Mota
Belén Navarro
Anabel Sáez
Pablo Valledor

Technicians

Marta Elena Antón
Alicia González
Sara Rodrigo

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.

Publications

Schlegel J, Porebski B, Andronico L, Hanke L, Edwards S, Brismar H, Murrell B, McInerney GM, Fernandez-Capetillo O, Sezgin E. (2023). A Multiparametric and High-Throughput Platform for Host-Virus Binding Screens. Nano Lett (in press). CNIO Publication.
Fueyo-Marcos E, Lopez-Pernas G, Fustero-Torre C, Antón ME, Al-Shahrour F, Fernández-Capetillo O, Murga M. (2023). PD-L1ATTAC mice reveal the potential of depleting PD-L1 expressing cells in cancer therapy. Aging (Albany NY) 15, 1791-1807. CNIO Publication.
Barz M, Porebski B, Panshikar P, Häggbladd M, Hühn D, Fernandez-Capetillo O. (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). CNIO Publication.
Galindo-Campos MA, Lutfi N, Bonnin S, Martínez C, Velasco-Hernandez T, García-Hernández V, Martin-Caballero J, Ampurdanés C, Gimeno R, Colomo L, Roue G, Guilbaud G, Dantzer F, Navarro P, Murga M, Fernandez-Capetillo O, Bigas A, Menendez P, Sale J, Yélamos J (2022). Distinct roles for PARP-1 and PARP-2 in c-Myc-driven B-cell lymphoma in mice.. Blood 139, 228-239. CNIO Publication.
Hanke L, Das H, Sheward DJ, Perez Vidakovics L, Urgard E, Moliner-Morro A, Kim C, Karl V, Pankow A, Smith NL, Porebski B, Fernandez-Capetillo O, Sezgin E, Pedersen GK, Coquet JM, Hällberg BM, Murrell B, McInerney GM (2022). A bispecific monomeric nanobody induces spike trimer dimers and neutralizes SARS-CoV-2 in vivo. Nat Commun 13, 155. CNIO Publication. Open Access
Corman A, Sirozh O, Lafarga V, Fernandez-Capetillo O. (2022). Targeting the nucleolus as a therapeutic strategy in human disease. Trends Biochem Sci (in press). CNIO Publication.
Sanchez-Burgos L, Navarro-González B, García-Martín S, Sirozh O, Mota-Pino J, Fueyo-Marcos E, Tejero H, Antón ME, Murga M, Al-Shahrour F, Fernandez-Capetillo O (2022). Activation of the integrated stress response is a vulnerability for multidrug-resistant FBXW7-deficient cells. EMBO Mol Med 0, e15855. CNIO Publication.
Hühn D, Martí-Rodrigo P, Mouron S, Hansel C, Tschapalda K, Porebski B, Häggblad M, Lidemalm L, Quintela-Fandino M, Carreras-Puigvert J, Fernandez-Capetillo O. (2022). Prolonged estrogen deprivation triggers a broad immunosuppressive phenotype in breast cancer cells. Mol Oncol 16, 148-165. CNIO Publication. Open Access
Murga M, Fernandez-Capetillo O (2022). Emerging concepts in drug discovery for cancer therapy. Mol Oncol 16, 3757-3760. CNIO Publication.
Egea J, López-Muñoz F, Fernández-Capetillo O, Reiter RJ, Romero A (2022). Alkylating Agent-Induced Toxicity and Melatonin-Based Therapies. Front Pharmacol 13, 873197. CNIO Publication.
Sanchez-Burgos L, Gómez-López G, Al-Shahrour F, Fernandez-Capetillo O (2022). An in silico analysis identifies drugs potentially modulating the cytokine storm triggered by SARS-CoV-2 infection.. Sci Rep 12, 1626. CNIO Publication. Open Access
Colicchia V, Häggblad M, Sirozh O, Porebski B, Balan M, Li X, Lidemalm L, Carreras-Puigvert J, Hühn D, Fernandez-Capetillo O (2022). New regulators of the tetracycline-inducible gene expression system identified by chemical and genetic screens. FEBS Open Bio 12, 1896-1908. CNIO Publication.
Galarreta A, Valledor P, Ubieto-Capella P, Lafarga V, Zarzuela E, Muñoz J, Malumbres M, Lecona E, Fernandez-Capetillo O (2021). USP7 limits CDK1 activity throughout the cell cycle. EMBO J 40, e99692. CNIO Publication.
Lafarga V, Sirozh O, Díaz-López I, Galarreta A, Hisaoka M, Zarzuela E, Boskovic J, Jovanovic B, Fernandez-Leiro R, Muñoz J, Stoecklin G, Ventoso I, Fernandez-Capetillo O (2021). Widespread displacement of DNA- and RNA-binding factors underlies toxicity of arginine-rich cell-penetrating peptides. EMBO J 40, e99692. CNIO Publication.
Franz A, Valledor P, Ubieto-Capella P, Pilger D, Galarreta A, Lafarga V, Fernández-Llorente A, de la Vega-Barranco G, den Brave F, Hoppe T, Fernandez-Capetillo O, Lecona E (2021). USP7 and VCP FAF1 define the SUMO/Ubiquitin landscape at the DNA replication fork. Cell Reports 37, 109819. CNIO Publication.
Corman A, Kanellis DC, Michalska P, Häggblad M, Lafarga V, Bartek J, Carreras-Puigvert J, Fernandez-Capetillo O (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.
Galarreta A, Valledor P, Fernandez-Capetillo O, Lecona E. (2021). Coordinating DNA Replication and Mitosis through Ubiquitin/SUMO and CDK1.. Int J Mol Sci 22, 8796. CNIO Publication.
Atashpaz S, Samadi Shams S, Gonzalez JM, Sebestyén E, Arghavanifard N, Gnocchi A, Albers E, Minardi S, Faga G, Soffientini P, Allievi E, Cancila V, Bachi A, Fernández-Capetillo Ó, Tripodo C, Ferrari F, López-Contreras AJ, Costanzo V (2020). ATR expands embryonic stem cell fate potential in response to replication stress. Elife 12, e54756. CNIO Publication. Open Access
Reglero C, Lafarga V, Rivas V, Albitre Á, Ramos P, Berciano SR, Tapia O, Martínez-Chantar ML, Mayor F Jr, Penela P (2020). GRK2-Dependent HuR Phosphorylation Regulates HIF1a Activation Under Hypoxia or Adrenergic Stress. Cancers 12, E1216. CNIO Publication. Open Access
Albers E, Avram A, Sbroggio M, Fernandez-Capetillo O, Lopez-Contreras AJ (2020). Supraphysiological protection from replication stress does not extend mammalian lifespan.. Aging (Albany NY) 12, 5612-5624. CNIO Publication.
Berciano MT, Castillo-Iglesias MS, Val-Bernal JF, Lafarga V, Rodriguez-Rey JC, Lafarga M, Tapia O (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.
Morales C, Ruiz-Torres M, Rodríguez-Acebes S, Lafarga V, Rodríguez-Corsino M, Megías D, Cisneros DA, Peters JM, Méndez J, Losada A (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
Lafarga V, Sung H-M, Haneke K, Roessig L, Pauleau A-L, Bruer M, Rodríguez-Acebes S, López-Contreras A, Gruss OJ, Erhardt S, Méndez J, Fernández-Capetillo O, Stoecklin G (2019). TIAR controls mitotic entry, maintains genome stability and retains CDK1 in checkpoint bodies.. EMBO Rep 20, pii: e46224. CNIO Publication.
Zong D, Adam S, Wang Y, Sasanuma H, Callén E, Murga M, Day A, Kruhlak MJ, Wong N, Munro M, Ray Chaudhuri A, Karim B, Xia B, Takeda S, Johnson N, Durocher D, Nussenzweig A (2019). BRCA1 Haploinsufficiency Is Masked by RNF168-Mediated Chromatin Ubiquitylation. Mol Cell 73, 1267-1281. CNIO Publication.
Olbrich T, Vega-Sendino M, Murga M, de Carcer G, Malumbres M, Ortega S, Ruiz S, Fernandez-Capetillo O (2019). A Chemical Screen Identifies Compounds Capable of Selecting for Haploidy in Mammalian Cells.. Cell Reports 28, 597-604. CNIO Publication. Open Access
Corman A, Jung B, Häggblad M, Bräutigam L, Lafarga V, Lidemalm L, Hühn D, Carreras-Puigvert J, Fernandez-Capetillo O (2019). A Chemical Screen Identifies Compounds Limiting the Toxicity of C9ORF72 Dipeptide Repeats. Cell Chem Biol 26, 235-243. CNIO Publication.
Lafarga V, Sung HM, Haneke K, Roessig L, Pauleau AL, Bruer M, Rodriguez-Acebes S, Lopez-Contreras AJ, Gruss OJ, Erhardt S, Mendez J, Fernandez-Capetillo O, Stoecklin G (2019). TIAR marks nuclear G2/M transition granules and restricts CDK1 activity under replication stress. EMBO Rep 20, e46224. CNIO Publication.
Baltanás FC, Berciano MT, Tapia O, Narcis JO, Lafarga V, Díaz D, Weruaga E, Santos E, Lafarga M (2019). Nucleolin reorganization and nucleolar stress in purkinje cells of mutant PCD mice. Neurobiol Dis 127, 312-322. CNIO Publication.
Lecona E, Fernandez-Capetillo O (2018). Targeting ATR in cancer. Nat Rev Cancer 18, 586-595. CNIO Publication.
Pacheco S, Maldonado-Linares A, Marcet-Ortega M, Rojas C, Martínez-Marchal M, Fuentes-Lazaro J, Lange J, Jasin M, Keeney S, Fernandez-Capetillo O, Garcia-Caldés M, Roig I (2018). ATR is required to complete meiotic recombination in mice. Nat Commun 9, 2622. CNIO Publication. Open Access
Mayor-Ruiz C, Olbrich T, Drosten M, Lecona E, Vega-Sendino M, Ortega S, Dominguez O, Barbacid M, Ruiz S, Fernandez-Capetillo O (2018). ERF deletion rescues RAS deficiency in mouse embryonic stem cells. Genes Dev 32, 568-576. CNIO Publication. Open Access
Lafarga V, Tapia O, Sharma S, Bengoechea R, Stoecklin G, Lafarga M, Berciano MT (2018). CBP-mediated SMN acetylation modulates Cajal body biogenesis and the cytoplasmic targeting of SMN. Cell Mol Life Sci 75, 527-576. CNIO Publication.
Lynch CJ, Bernad R, Calvo I, Nóbrega-Pereira S, Ruiz S, Ibarz N, Martinez-Val A, Graña-Castro O, Gómez-López G, Andrés-León E, Espinosa Angarica V, Del Sol A, Ortega S, Fernandez-Capetillo O, Rojo E, Munoz J, Serrano M (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
Galarreta A, Lecona E, Valledor P, Ubieto P, Lafarga V, Specks J, Fernandez-Capetillo O (2018). USP7 couples DNA replication termination to mitotic entry. bioRxiv (in press). CNIO Publication.
Lafarga V, Sirozh O, Diaz-Lopez I, Hisaoka M, Zarzuela E, Boskovic J, Jovanovic B, Fernandez-Leiro R, Munoz J, Stoecklin G, Ventoso I, Fernandez-Capetillo O (2018). DNA and RNA binding mediate the toxicity of arginine-rich peptides encoded by C9ORF72 GGGGCC repeats. bioRxiv (in press). CNIO Publication.