Genomic Instability Group

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

Research Scientists

Vanesa Lafarga
Matilde Murga

Post-Doctoral Fellows

Ivó Hernández

Graduate Students

Julia Carballeira
Amin El Manchoud
Gema López
Mario López
Ana Martínez
Jorge Mota
Belén Navarro
Anabel Sáez

Technicians

Marta Elena Antón
Alicia González
Sara Rodrigo

The research interests of our Group have evolved over the years, while always centred on trying to decipher the molecular mechanisms that drive cancer and other age-related diseases. We initially focused on studying replication stress (RS), a form of DNA damage sensed and controlled by the ATR kinase, which we revealed plays a central role in cancer and ageing. Amongst other achievements, we developed novel ATR inhibitors and contributed to elucidating their mechanism of action and the molecular determinants of resistance to these drugs. From this early work, we developed a growing interest in the molecular mechanisms that drive resistance to cancer therapies, a major challenge in oncology. Beyond basic science, we use this knowledge to develop novel treatments targeting therapy-resistant cancer cells.

Recent publications

Sirozh O, Saez-Mas A, Jung B, Sanchez-Burgos L, Zarzuela E, Rodrigo-Perez S, Ventoso I, Lafarga V, Fernandez-Capetillo O. (2024). Nucleolar stress caused by arginine-rich peptides triggers a ribosomopathy and accelerates aging in mice. Mol Cell 84, 1527-1540. CNIO Publication.
Porebski B, Christ W, Corman A, Haraldsson M, Barz M, Lidemalm L, Häggblad M, Ilmain J, Wright SC, Murga M, Schlegel J, Jarvius M, Lapins M, Sezgin E, Bhabha G, Lauschke VM, Carreras-Puigvert J, Lafarga M, Klingström J, Hühn D, Fernandez-Capetillo O. (2024). Discovery of a novel inhibitor of macropinocytosis with antiviral activity. Mol Ther 32, 3012-3024. CNIO Publication.
Li X, Hernandez I, Koyuncu S, Kis B, Häggblad M, Lidemalm L, Abbas AA, Bendegúz S, Göblös A, Brautigam L, Lucas JJ, Carreras-Puigvert J, Hühn D, Pircs K, Vilchez D, Fernandez-Capetillo O. (2024). The anti-leprosy drug clofazimine reduces polyQ toxicity through activation of PPARγ. EBioMedicine 103, 105124. CNIO Publication.
Protasoni M, López-Polo V, Stephan-Otto Attolini C, Brandariz J, Herranz N, Mateo J, Ruiz S, Fernandez-Capetillo O, Kovatcheva M, Serrano M. (2024). Cyclophilin D plays a critical role in the survival of senescent cells. EMBO J 43, 5972-6000. CNIO Publication.
Murga M, Lopez-Pernas G, Soliva R, Fueyo-Marcos E, Amor C, Faustino I, Serna M, Serrano AG, Díaz L, Martínez S, Blanco-Aparicio C, Antón ME, Seashore-Ludlow B, Pastor J, Jafari R, Lafarga M, Llorca O, Orozco M, Fernández-Capetillo O. (2024). SETD8 inhibition targets cancer cells with increased rates of ribosome biogenesis. Cell Death Dis 15, 694. CNIO Publication. Open Access
Rivas V, González-Muñoz T, Albitre Á, Lafarga V, Delgado-Arévalo C, Mayor F Jr, Penela P. (2024). GRK2-mediated AKT activation controls cell cycle progression and G2 checkpoint in a p53-dependent manner. Cell Death Dis 10, 385. CNIO Publication.
Kanellis DC, Zisi A, Skrott Z, Lemmens B, Espinoza JA, Kosar M, Björkman A, Li X, Arampatzis S, Bartkova J, Andújar-Sánchez M, Fernandez-Capetillo O, Mistrik M, Lindström MS, Bartek J. (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. CNIO Publication. Open Access
Sayago C, Sánchez-Wandelmer J, García F, Hurtado B, Lafarga V, Prieto P, Zarzuela E, Ximénez-Embún P, Ortega S, Megías D, Fernández-Capetillo O, Malumbres M, Munoz J. (2023). Decoding protein methylation function with thermal stability analysis.. Nat Commun 14, 3016. CNIO Publication. Open Access
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 23, 3701-3707. 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. Open Access
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. Open Access
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. Open Access
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. Open Access
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.