María A. Blasco Group Leader
T +34 917328032 (Ext 3400)
mblasco@cnio.es

We study the mechanisms by which tumour cells are immortal and normal cells are mortal. Immortality is one of the most universal characteristics of cancer cells. The enzyme telomerase is present in more than 95% of all types of human cancers and absent in normal cells in the body. Telomeres are nucleoprotein complexes located at the ends of chromosomes, essential for chromosome protection and genomic stability.

Progressive shortening of telomeres associated with organism ageing leads to ageing. When telomeres are altered, adult stem cells have a maimed regenerative capacity.

Our research focuses on:

• Generating mouse models to validate telomeres and telomerase as therapeutic targets for cancer and agerelated diseases.
• The interplay between telomeres and DNA repair pathways.
• The role and regulation of non-coding telomeric RNAs or TERRA.
• Testing telomerase gene therapy in ‘telomere syndromes’and age-related diseases.
• The role of telomerase and telomeres in adult stem cell biology and in nuclear reprogramming of differentiated cells to iPS cells.

Publications

• Salazar-Roa M, Trakala M, Álvarez-Fernández M, Valdés-Mora F, Zhong C, Muñoz J, Yu Y, Peters TJ, Graña-Castro O, Serrano R, Zapatero-Solana E, Abad M, Bueno MJ, de Cedrón MG, Fernández-Piqueras J, Serrano M, Blasco MA, Wang DZ, Clark SJ, Izpisua-Belmonte JC, Ortega S, Malumbres M (2020). Transient Exposure to miR-203 Enhances the Differentiation Capacity of Established Pluripotent Stem Cells. EMBO J (in press). CNIO Publication.
• Whittemore K, Blasco MA (2020). Reply to Udroiu: Interesting Mathematical Analysis of Telomere Shortening Rate and Life Span. Proc Natl Acad Sci USA 117, 2250. CNIO Publication.
• Kordowitzki P, Silanes IL, Guío-Carrión A, Blasco MA (2020). Dynamics of telomeric repeat-containing RNA expression in early embryonic cleavage stages with regards to maternal age. Aging (Albany NY) (in press). CNIO Publication.
• Klett J, Gómez-Casero E, Méndez-Pertuz M, Urbano-Cuadrado M, Megias D, Blasco MA, Martínez S, Pastor J, Blanco-Aparicio C (2020). Screening protocol for the identification of modulators by immunofluorescent cell-based assay. Chem Biol Drug Des 95, 66-78. CNIO Publication.
• Callen E, Zong D , Wu W, Wong N, Stanlie A , Ishikawa M , Pavani R , Dumitrache LC , Byrum AK , Mendez-Dorantes C, Martinez P , Canela A , Maman Y, Day A , Kruhlak MJ, Blasco MA , Stark JM, Mosammaparast N, McKinnon PJ, Nussenzweig A (2020). 53BP1 Enforces Distinct Pre- And Post-resection Blocks on Homologous Recombination. Mol Cell 77, 26-38. CNIO Publication.
• Ferrara-Romeo I, Martinez P, Saraswati S, Whittemore K, Graña-Castro O, Thelma Poluha L, Serrano R, Hernandez-Encinas E, Blanco-Aparicio C, Maria Flores J, Blasco MA (2020). The mTOR pathway is necessary for survival of mice with short telomeres.. Nat Commun 11, 1168. CNIO Publication. Open Access
• Kordowitzki P, Hamdi M, Derevyanko A, Rizos D, Blasco M (2020). The effect of rapamycin on bovine oocyte maturation success and metaphase telomere length maintenance.. Aging (Albany NY) 12, 7576-7584. CNIO Publication.
• Whittemore K, Derevyanko A, Martinez P, Serrano R, Pumarola M, Bosch F, Blasco MA (2019). Telomerase gene therapy ameliorates the effects of neurodegeneration associated to short telomeres in mice. Aging (Albany NY) 11, 2916-2948. CNIO Publication.
• Bejarano L, Bosso G, Louzame J, Serrano R, Gómez-Casero E, Martínez-Torrecuadrada J, Martínez S, Blanco-Aparicio C, Pastor J, Blasco MA (2019). Multiple cancer pathways regulate telomere protection.. EMBO Mol Med 11, e10292. CNIO Publication. Open Access
• Perales-Puchalt A, Soberón N, Monterde M, Hervas-Marin D, Foronda M, Desantes D, Soler I, Perales-Marin A, Pellicer A, Blasco MA (2019). Maternal telomere length is shorter in intrauterine growth restriction versus uncomplicated pregnancies, but not in the offspring or in IVF-conceived newborns. Reprod Biomed Online 38, 606-612. CNIO Publication.
• Whittemore K, Vera E, Martínez-Nevado E, Sanpera C, Blasco MA (2019). Telomere shortening rate predicts species life span.. Proc Natl Acad Sci USA 116, 15122-15127. CNIO Publication.
• Bejarano L, Louzame J, Montero JJ, Megías D, Flores JM, Blasco MA (2019). Safety of Whole-Body Abrogation of the TRF1 Shelterin Protein in Wild-Type and Cancer-Prone Mouse Models.. iScience 19, 572-585. CNIO Publication. Open Access
• Freitas-Simoes TM, Cofán M, Blasco MA, Soberón N, Foronda M, Corella D, Asensio EM, Serra-Mir M, Roth I, Calvo C, Valls-Pedret C, Casaroli-Marano RP, Doménech M, Rajaram S, Sabaté J, Ros E, Sala-Vila A (2019). The red blood cell proportion of arachidonic acid relates to shorter leukocyte telomeres in Mediterranean elders: A secondary analysis of a randomized controlled trial. Clin Nutr 38, 958-961. CNIO Publication.
• Muñoz-Lorente MA, Cano-Martin AC, Blasco MA (2019). Mice with hyper-long telomeres show less metabolic aging and longer lifespans. Nat Commun 10, 4723. CNIO Publication. Open Access
• Marión RM, Montero JJ, López de Silanes I, Graña-Castro O, Martínez P, Schoeftner S, Palacios-Fábrega JA, Blasco MA (2019). TERRA regulate the transcriptional landscape of pluripotent cells through TRF1-dependent recruitment of PRC2. Elife 8, e44656. CNIO Publication. Open Access
• Whittemore K , Eva Martínez-Nevado E, Blasco MA (2019). Slower Rates of Accumulation of DNA Damage in Leukocytes Correlate With Longer Lifespans Across Several Species of Birds and Mammals. Aging (Albany NY) 11, 9829-9845. CNIO Publication.
• Freitas-Simoes TM, Cofán M, Blasco MA, Soberón N, Foronda M, Serra-Mir M, Roth I, Valls-Pedret C, Doménech M, Ponferrada-Ariza E, Calvo C, Rajaram S, Sabaté J, Ros E, Sala-Vila A (2018). Walnut Consumption for Two Years and Leukocyte Telomere Attrition in Mediterranean Elders: Results of a Randomized Controlled Trial. Nutrients 10, pii: E1907. CNIO Publication. Open Access
• Montero JJ, López-Silanes I, Megías D, F Fraga M, Castells-García Á, Blasco MA (2018). TERRA recruitment of polycomb to telomeres is essential for histone trymethylation marks at telomeric heterochromatin. Nat Commun 9, 1548. CNIO Publication. Open Access
• Martínez P, Blasco MA (2018). Heart-Breaking Telomeres. Circ Res 123, 787-802. CNIO Publication.
• Povedano JM, Martinez P, Serrano R, Tejera Á, Gómez-López G, Bobadilla M, Flores JM, Bosch F, Blasco MA (2018). Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres. Elife 7, e31299. CNIO Publication. Open Access
• Muñoz-Lorente MA, Martínez P, Tejera Á, Whittemore K, Moisés-Silva AC, Bosch F, Blasco MA (2018). AAV9-mediated telomerase activation does not accelerate tumorigenesis in the context of oncogenic K-Ras-induced lung cancer. Plos Genetics 14, e1007562. CNIO Publication. Open Access
• Ferrara-Romeo I, Martínez P, Blasco MA (2018). Mice lacking RAP1 show early onset and higher rates of DEN-induced hepatocellular carcinomas in female mice. PLoS One 13, e0204909. CNIO Publication. Open Access
• Bejarano L, Schuhmacher AJ, Méndez-Pertuz M, Megías M, Blanco-Aparicio C, Martínez S, Pastor J, Squatrito M, Blasco MA (2017). Inhibition of Trf1 telomere protein impairs tumor initiation and progression in glioblastoma multiform mouse models and patient-derived xenografts.. Cancer Cell 32, 590-607. CNIO Publication.
• Méndez-Pertuz M, Martínez P, Blanco-Aparicio C, Gómez-Casero E, García AB, Martínez -Torrecuadrada J, Palafox M, Cortés J, Serra V, Pastor J, Blasco MA (2017). Modulation of telomere protection by the PI3K/AKT pathway. Nat Commun 8, 1278. CNIO Publication. Open Access
• Marión RM, Blasco MA (2017). Long Live Partial Reprogramming.. Circ Res 120, 1381-1383. CNIO Publication.
• Martínez P, Blasco MA (2017). Telomere-driven diseases and telomere-targeting therapies. J Cell Biol 216, 875-887. CNIO Publication. Open Access
• Marión RM, López de Silanes I, Mosteiro L, Gamache B, Abad M, Guerra C, Megías D, Serrano M, Blasco MA (2017). Common Telomere Changes during In Vivo Reprogramming and Early Stages of Tumorigenesis. Stem Cell Reports 8, 460-475. CNIO Publication.
• Aguado T, Gutiérrez FJ, Aix E, Schneider RP, Giovinnazo G, Blasco MA, Flores I. (2017). Telomere length defines the cardiomyocyte differentiation potency of mouse induced pluripotent stem cells.. Stem Cells 35, 362-373. CNIO Publication.
• Derevyanko A, Whittemore K, Schneider RP, Jiménez V, Bosch F, Blasco MA (2017). Gene therapy with the TRF1 telomere gene rescues decreased TRF1 levels with aging and prolongs mouse health span. Aging Cell 16, 1353-1368. CNIO Publication.
• Quintela-Fandino M, Soberon N, Lluch A, Manso L, Calvo I, Cortes J, Moreno-Antón F, Gil-Gil M, Martinez-Jánez N, Gonzalez-Martin A, Adrover E, de Andres R, Viñas G, Llombart-Cussac A, Alba E, Mouron S, Guerra J, Bermejo B, Zamora E, García-Saenz JA, Simon SP, Carrasco E, Escudero MJ, Campo R, Colomer R, Blasco MA (2017). Critically short telomeres and toxicity of chemotherapy in early breast cancer. Oncotarget 8, 21472-21842. CNIO Publication.
• Kannappan R, Matsuda A, Ferreira-Martins J, Zhang E, Palano G, Czarna A, Cabral-Da-Silva MC, Bastos-Carvalho A, Sanada F, Ide N, Rota M, Blasco MA, Serrano M, Anversa P, Leri A (2017). p53 Modulates the Fate of Cardiac Progenitor Cells Ex Vivo and in the Diabetic Heart In Vivo. EBioMedicine 16, 224-237. CNIO Publication.
• Mosteiro LL, Pantoja C, Alcazar N, Marión RM, Chondronasiou D, Rovira M, Fernandez-Marcos PJ, Muñoz-Martin M, Blanco-Aparicio C, Pastor J, Gómez-López G, de Martino A, Blasco MA, Abad M, Serrano M (2016). Tissue damage and senescence provide critical signals for cellular reprogramming in vivo.. Science 354, pii: aaf4445.. CNIO Publication.
• Fernández-Alvira JM, Fuster V, Dorado B, Soberón N, Flores I, Gallardo M, Pocock S, Blasco MA, Andrés V (2016). Short Telomere Load, Telomere Length, and Subclinical Atherosclerosis: The PESA Study.. J Am Coll Cardiol 67, 2467-2476. CNIO Publication.
• Montero JJ, López de Silanes I, Graña O, Blasco MA (2016). Telomeric RNAs are essential to maintain telomeres. Nat Commun 7, 12534. CNIO Publication. Open Access
• Varela E, Muñoz-Lorente MA, Tejera AM, Ortega S, Blasco MA (2016). Generation of mice with longer and better preserved telomeres in the absence of genetic manipulations. Nat Commun 7, 11739. CNIO Publication. Open Access
• Bär C, Povedano JM, Serrano R, Benitez-Buelga C, Popkes M, Formentini I, Bobadilla M, Bosch F, Blasco MA (2016). Telomerase gene therapy rescues telomere length, bone marrow aplasia and survival in mice with aplastic anemia.. Blood 127, 1770-1779. CNIO Publication.
• Martínez P, Gómez-López G, Pisano DG, Flores JM, Blasco MA (2016). A genetic interaction between RAP1 and telomerase reveals an unanticipated role for RAP1 in telomere maintenance. Aging Cell 15, 1113-1125. CNIO Publication. Open Access
• Benitez-Buelga C, Vaclová T, Ferreira S, Urioste M, Inglada-Perez L, Soberón N, Blasco MA, Osorio A, Benitez J (2016). Molecular insights into the OGG1 gene, a cancer risk modifier in BRCA1 and BRCA2 mutations carriers. Oncotarget 7, 25815-25825. CNIO Publication. Open Access
• Boskovic J, Martinez-Gago J, Mendez-Pertuz M, Buscato A, Martinez-Torrecuadrada JL, Blasco MA (2016). Molecular Architecture of Full Length TRF1 Favors its Interaction with DNA.. J Biol Chem 291, 21829-21835. CNIO Publication.
• Comino-Méndez I, Tejera ÁM, Currás-Freixes M, Remacha L, Gonzalvo P, Tonda R, Letón R, Blasco MA, Robledo M, Cascón A (2016). ATRX driver mutation in a composite malignant pheochromocytoma.. Cancer Genet 209, 272-277. CNIO Publication.
• Bär C, Blasco MA (2016). Telomeres and telomerase as therapeutic targets to prevent and treat age-related diseases.. F1000Res 20, 5. CNIO Publication.
• García-Beccaria M, Martínez P, Méndez-Pertuz M, Martínez S, Blanco-Aparicio C, Cañamero M, Mulero F, Ambrogio C, Flores JM, Megias D, Barbacid M, Pastor J, Blasco MA (2015). Therapeutic inhibition of TRF1 impairs the growth of p53-deficient K-RasG12V-induced lung cancer by induction of telomeric DNA damage. EMBO Mol Med 7, 930-949. CNIO Publication. Open Access
• Mouraret N, Houssaini A, Abid S, Quarck R, Marcos E, Parpaleix A, Gary-Bobo G, Dubois-Rande J, Derumeaux G, Boczkowski J, Delcroix M, Blasco MA, Lipskaia LL, Amsellem V, Adnot S (2015). Role for Telomerase in Pulmonary Hypertension.. Circulation 131, 742-745. CNIO Publication.
• Calvete O, Martinez P, Garcia-Pavia P, Benitez-Buelga C, Paumard-Hernández B, Fernandez V, Dominguez F, Salas C, Romero-Laorden N, Garcia-Donas J, Carrillo J, Perona R, Triviño JC, Andrés R, Cano JM, Rivera B, Alonso-Pulpon L, Setien F, Esteller M, Rodriguez-Perales S, Bougeard G, Frebourg T, Urioste M, Blasco MA, Benítez J (2015). A mutation in the POT1 gene is responsible for cardiac angiosarcoma in TP53-negative Li-Fraumeni-like families. Nat Commun 6, 8383. CNIO Publication. Open Access
• Giraddi RR, Shehata M, Gallardo M, Blasco MA, Simons BD, Stingl J (2015). Stem and progenitor cell division kinetics during postnatal mouse mammary gland development. Nat Commun 6, 8487. CNIO Publication. Open Access
• Ruiz S, Lopez-Contreras AJ, Gabut M, Marion RM, Gutierrez-Martinez P, Bua S, Ramirez O, Olalde I, Rodrigo-Perez S, Li H, Marques-Bonet T, Serrano M, Blasco MA, Batada NN, Fernandez-Capetillo O (2015). Limiting replication stress during somatic cell reprogramming reduces genomic instability in induced pluripotent stem cells. Nat Commun 6, 8036. CNIO Publication. Open Access
• Scarola M, Comisso E, Pascolo R, Chiaradia R, Maria Marion R, Schneider C, Blasco MA, Schoeftner S, Benetti R (2015). Epigenetic silencing of Oct4 by a complex containing SUV39H1 and Oct4 pseudogene lncRNA. Nat Commun 6, 7631. CNIO Publication. Open Access
• Sedic M, Skibinski A, Brown N, Gallardo M, Mulligan P, Martinez P, Keller PJ, Glover E, Richardson AL, Cowan J, Toland AE, Ravichandran K, Riethman H, Naber SP, Näär AM, Blasco MA, Hinds PW, Kuperwasser C (2015). Haploinsufficiency for BRCA1 leads to cell-type-specific genomic instability and premature senescence. Nat Commun 6, 7505. CNIO Publication. Open Access
• Beier F, Martinez P, Blasco MA (2015). Chronic replicative stress induced by CCL4 in TRF1 knockout mice recapitulates the origin of large liver cell changes.. J Hepatol 63, 446-455. CNIO Publication.
• Martínez P, Blasco MA (2015). Replicating through telomeres: a means to an end. Trends Biochem Sci 40, 504-515. CNIO Publication.
• Hummel S, Ventura Ferreira MS, Heudobler D, Huber E, Fahrenkamp D, Gremse F, Schmid K, Müller-Newen G, Ziegler P, Jost E, Blasco MA, Brümmendorf TH, Holler E, Beier F (2015). Telomere shortening in enterocytes of patients with uncontrolled acute intestinal graft-versus-host disease. Blood 126, 2518-2521. CNIO Publication.
• Jacome A, Gutierrez-Martinez P, Schiavoni F, Tenaglia E, Martinez P, Rodríguez-Acebes S, Lecona E, Murga M, Méndez J, Blasco MA, Fernandez-Capetillo O (2015). NSMCE2 suppresses cancer and aging in mice independently of its SUMO ligase activity.. EMBO J 34, 2604-2619. CNIO Publication.
• González-García MP, Pavelescu I, Canela A, Sevillano X, Leehy KA, Nelson AD, Ibañes M, Shippen DE, Blasco MA, Caño-Delgado AI (2015). Single-cell telomere-length quantification couples telomere length to meristem activity and stem cell development in Arabidopsis. Cell Reports 11, 977-989. CNIO Publication.
• Povedano JM, Martinez P, Flores JM, Mulero F, Blasco MA (2015). Mice with Pulmonary Fibrosis Driven by Telomere Dysfunction. Cell Reports 12, 286-299. CNIO Publication. Open Access
• Bär C, Huber N, Beier F, Blasco MA. (2015). Therapeutic effect of androgen therapy in a mouse model of aplastic anemia produced by short telomeres.. Haematologica 100, 1267-1274. CNIO Publication.
• Petti E, Jordi F, Buemi V, Dinami R, Benetti R, Blasco MA, Schoeftner S (2015). Altered telomere homeostasis and resistance to skin carcinogenesis in Suv39h1 transgenic mice.. Cell Cycle 14, 1438-1446. CNIO Publication.
• Benitez-Buelga C, Sanchez-Barroso L, Gallardo M, Apellániz-Ruiz M, Inglada-Pérez L, Yanowski K, Carrillo J, Garcia-Estevez L, Calvo I, Perona R, Urioste M, Osorio A, Blasco MA, Rodriguez-Antona C, Benitez J (2015). Impact of chemotherapy on telomere length in sporadic and familial breast cancer patients.. Breast Cancer Res Treat 149, 385-394. CNIO Publication.
• Beier F, Masouleh BK, Buesche G, Ventura Ferreira MS, Schneider RK, Ziegler P, Wilop S, Vankann L, Gattermann N, Platzbecker U, Giagounidis A, Götze KS, Nolte F, Hofmann WK, Haase D, Kreipe H, Panse J, Blasco MA, Germing U, Brümmendorf TH (2015). Telomere dynamics in patients with del (5q) MDS before and under treatment with lenalidomide.. Leuk Res (in press). CNIO Publication.
• Foronda M, Morgado-Palacin L, Gómez-López G, Domínguez O, Pisano DG, Blasco MA (2015). Profiling of Sox4-dependent transcriptome in skin links tumour suppression and adult stem cell activation. GENOMICS DATA 6, 21-24. CNIO Publication.