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

• Sanchez-Vazquez R, Guío-Carrión A, Zapatero-Gaviria A, Martínez P, Blasco MA (2021). Shorter telomere lengths in patients with severe COVID-19 disease. Aging (Albany NY) 13, 1-15. CNIO Publication.
• Piñeiro-Hermida S, Martínez P, Blasco MA (2021). Short and dysfunctional telomeres protect from allergen-induced airway inflammation. Aging Cell 20, e13352. CNIO Publication.
• Sánchez-Vázquez R, Martínez P, Blasco MA (2021). AKT-dependent signaling of extracellular cues through telomeres impact on tumorigenesis. Plos Genetics 17, e1009410. CNIO Publication.
• Alvarez-Palomo AB, Requena-Osete J, Delgado-Morales R, Moreno-Manzano V, Grau-Bove C, Tejera AM, Otero MJ, Barrot C, Santos-Barriopedro I, Vaquero A, Mezquita-Pla J, Moran S, Naya CH, Garcia-Martínez I, Pérez FV, Blasco MA, Esteller M, Edel MJ (2021). A synthetic mRNA cell reprogramming method using CYCLIN D1 promotes DNA repair generating improved genetically stable human induced pluripotent stem cells. Stem Cells (in press). CNIO Publication.
• Vinchure OS, Whittemore K, Kushwah D, Blasco MA, Kulshreshtha R (2021). miR-490 suppresses telomere maintenance program and associated hallmarks in glioblastoma. Cell Mol Life Sci 78, 2299-2314. CNIO Publication.
• Alvarez-Palomo AB, Requena-Osete J, Delgado-Morales R, Moreno-Manzano V, Grau-Bove C, Tejera AM, Otero MJ, Barrot C, Santos-Barriopedro I, Vaquero A, Mezquita-Pla J, Moran S, Naya CH, Garcia-Martínez I, Pérez FV, Blasco MA, Esteller M, Edel MJ (2021). Ageing affects subtelomeric DNA methylation in blood cells from a large European population enrolled in the MARK-AGE study. Stem Cells 39, 866-881. CNIO Publication.
• 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 39, e104324. 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) 12, 15906-15917. CNIO Publication. Open Access
• 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.
• Piñeiro-Hermida S, Autilio C, Martínez P, Bosch F, Pérez-Gil J, Blasco MA (2020). Telomerase treatment prevents lung profibrotic pathologies associated with physiological aging. J Cell Biol 219, e202002120.. 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.
• Fuentes-Fayos AC, Vázquez-Borrego MC, Jiménez-Vacas JM, Bejarano L, Pedraza-Arévalo S, L-López F, Blanco-Acevedo C, Sánchez-Sánchez R, Reyes O, Ventura S, Solivera J, Breunig JJ, Blasco MA, Gahete MD, Castaño JP, Luque RM. (2020). Splicing machinery dysregulation drives glioblastoma development/aggressiveness: oncogenic role of SRSF3. Brain 143, 3273-3293. CNIO Publication.
• Calvete O, Mouron S, Barroso A, Soberon N, Blasco MA , Quintela-Fandino M, Benítez J (2020). Long telomeres: A new prognostic factor for severity in triple-negative breast cancer patients. J Transl Sci (in press). 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.