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 age-related 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

• TERRA recruitment of polycomb to telomeres is essential for histone trymethylation marks at telomeric heterochromatin.(2018)
  Montero JJ, López-Silanes I, Megías D, F Fraga M, Castells-García Á, Blasco MA.
  Nat Commun 9, 1548-.
• Heart-Breaking Telomeres.(2018)
  Martínez P, Blasco MA.
  Circ Res 123, 787-802.
• Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres.(2018)
  Povedano JM, Martinez P, Serrano R, Tejera Á, Gómez-López G, Bobadilla M, Flores JM, Bosch F, Blasco MA.
  Elife 7, e31299-.
• AAV9-mediated telomerase activation does not accelerate tumorigenesis in the context of oncogenic K-Ras-induced lung cancer.(2018)
  Muñoz-Lorente MA, Martínez P, Tejera Á, Whittemore K, Moisés-Silva AC, Bosch F, Blasco MA.
  Plos Genetics 14, e1007562-.
• The red blood cell proportion of arachidonic acid relates to shorter leukocyte telomeres in Mediterranean elders: A secondary analysis of a randomized controlled trial.(2018)
  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.
  Clin Nutr (in press).
• Mice lacking RAP1 show early onset and higher rates of DEN-induced hepatocellular carcinomas in female mice.(2018)
  Ferrara-Romeo I, Martínez P, Blasco MA
  PLoS ONE 13, e0204909-.
• Walnut Consumption for Two Years and Leukocyte Telomere Attrition in Mediterranean Elders: Results of a Randomized Controlled Trial.(2018)
  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.
  Nutrients 10, pii: E1907-.
• Inhibition of Trf1 telomere protein impairs tumor initiation and progression in glioblastoma multiform mouse models and patient-derived xenografts.(2017)
  Bejarano L, Schuhmacher AJ, Méndez-Pertuz M, Megías M, Blanco-Aparicio C, Martínez S, Pastor J, Squatrito M, Blasco MA
  Cancer Cell 32, 590-607.
• Modulation of telomere protection by the PI3K/AKT pathway.(2017)
  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
  Nat Commun 8, 1278-.
• Long Live Partial Reprogramming.(2017)
  Marión RM, Blasco MA
  Circ Res 120, 1381-1383.
• Telomere-driven diseases and telomere-targeting therapies.(2017)
  Martínez P, Blasco MA.
  J Cell Biol 216, 875-887.
• Common Telomere Changes during In Vivo Reprogramming and Early Stages of Tumorigenesis.(2017)
  Marión RM, López de Silanes I, Mosteiro L, Gamache B, Abad M, Guerra C, Megías D, Serrano M, Blasco MA.
  Stem Cell Reports 8, 460-475.
• Telomere length defines the cardiomyocyte differentiation potency of mouse induced pluripotent stem cells.(2017)
  Aguado T, Gutiérrez FJ, Aix E, Schneider RP, Giovinnazo G, Blasco MA, Flores I.
  Stem Cells 35, 362-373.
• Gene therapy with the TRF1 telomere gene rescues decreased TRF1 levels with aging and prolongs mouse health span.(2017)
  Derevyanko A, Whittemore K, Schneider RP, Jiménez V, Bosch F, Blasco MA
  Aging Cell 16, 1353-1368.
• Critically short telomeres and toxicity of chemotherapy in early breast cancer.(2017)
  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
  Oncotarget 8, 21472-21842.
• p53 Modulates the Fate of Cardiac Progenitor Cells Ex Vivo and in the Diabetic Heart In Vivo.(2017)
  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
  EBioMedicine 16, 224-237.
• Tissue damage and senescence provide critical signals for cellular reprogramming in vivo.(2016)
  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
  Science 354, pii: aaf4445.-0.
• Short Telomere Load, Telomere Length, and Subclinical Atherosclerosis: The PESA Study.(2016)
  Fernández-Alvira JM, Fuster V, Dorado B, Soberón N, Flores I, Gallardo M, Pocock S, Blasco MA, Andrés V
  J Am Coll Cardiol 67, 2467-2476.
• Telomeric RNAs are essential to maintain telomeres.(2016)
  Montero JJ, López de Silanes I, Graña O, Blasco MA
  Nat Communications 7, 12534-.
• Generation of mice with longer and better preserved telomeres in the absence of genetic manipulations.(2016)
  Varela E, Muñoz-Lorente MA, Tejera AM, Ortega S, Blasco MA
  Nat Communications 7, 11739-.
• Telomerase gene therapy rescues telomere length, bone marrow aplasia and survival in mice with aplastic anemia.(2016)
  Bär C, Povedano JM, Serrano R, Benitez-Buelga C, Popkes M, Formentini I, Bobadilla M, Bosch F, Blasco MA
  Blood 127, 1770-1779.
• A genetic interaction between RAP1 and telomerase reveals an unanticipated role for RAP1 in telomere maintenance.(2016)
  Martínez P, Gómez-López G, Pisano DG, Flores JM, Blasco MA
  Aging Cell (in press).
• Molecular insights into the OGG1 gene, a cancer risk modifier in BRCA1 and BRCA2 mutations carriers.(2016)
  Benitez-Buelga C, Vaclová T, Ferreira S, Urioste M, Inglada-Perez L, Soberón N, Blasco MA, Osorio A, Benitez J
  Oncotarget 7, 25815-25825.
• Molecular Architecture of Full Length TRF1 Favors its Interaction with DNA.(2016)
  Boskovic J, Martinez-Gago J, Mendez-Pertuz M, Buscato A, Martinez-Torrecuadrada JL, Blasco MA
  J Biol Chem 291, 21829-21835.
• ATRX driver mutation in a composite malignant pheochromocytoma.(2016)
  Comino-Méndez I, Tejera ÁM, Currás-Freixes M, Remacha L, Gonzalvo P, Tonda R, Letón R, Blasco MA, Robledo M, Cascón A
  Cancer Genet 209, 272-277.
• Telomeres and telomerase as therapeutic targets to prevent and treat age-related diseases.(2016)
  Bär C, Blasco MA
  F1000Res 20, 5-.
• Therapeutic inhibition of TRF1 impairs the growth of p53-deficient K-RasG12V-induced lung cancer by induction of telomeric DNA damage.(2015)
  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
  EMBO Mol Med 7, 930-949.
• Role for Telomerase in Pulmonary Hypertension.(2015)
  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
  Circulation 131, 742-745.
• A mutation in the POT1 gene is responsible for cardiac angiosarcoma in TP53-negative Li-Fraumeni-like families.(2015)
  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.
  Nat Communications 6, 8383-.
• Stem and progenitor cell division kinetics during postnatal mouse mammary gland development.(2015)
  Giraddi RR, Shehata M, Gallardo M, Blasco MA, Simons BD, Stingl J
  Nat Communications 6, 8487-.
• Limiting replication stress during somatic cell reprogramming reduces genomic instability in induced pluripotent stem cells.(2015)
  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
  Nat Communications 6, 8036-.
• Epigenetic silencing of Oct4 by a complex containing SUV39H1 and Oct4 pseudogene lncRNA.(2015)
  Scarola M, Comisso E, Pascolo R, Chiaradia R, Maria Marion R, Schneider C, Blasco MA, Schoeftner S, Benetti R
  Nat Communications 6, 7631-.
• Haploinsufficiency for BRCA1 leads to cell-type-specific genomic instability and premature senescence.(2015)
  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
  Nat Communications 6, 7505-.
• Chronic replicative stress induced by CCL4 in TRF1 knockout mice recapitulates the origin of large liver cell changes.(2015)
  Beier F, Martinez P, Blasco MA
  J Hepatol 63, 446-455.
• Replicating through telomeres: a means to an end.(2015)
  Martínez P, Blasco MA
  Trends Biochem Sci 40, 504-515.
• Telomere shortening in enterocytes of patients with uncontrolled acute intestinal graft-versus-host disease(2015)
  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
  Blood 126, 2518-2521.
• NSMCE2 suppresses cancer and aging in mice independently of its SUMO ligase activity.(2015)
  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
  EMBO J 34, 2604-2619.
• Single-cell telomere-length quantification couples telomere length to meristem activity and stem cell development in Arabidopsis.(2015)
  González-García MP, Pavelescu I, Canela A, Sevillano X, Leehy KA, Nelson AD, Ibañes M, Shippen DE, Blasco MA, Caño-Delgado AI
  Cell Reports 11, 977-989.
• Mice with Pulmonary Fibrosis Driven by Telomere Dysfunction.(2015)
  Povedano JM, Martinez P, Flores JM, Mulero F, Blasco MA
  Cell Reports 12, 286-299.
• Therapeutic effect of androgen therapy in a mouse model of aplastic anemia produced by short telomeres.(2015)
  Bär C, Huber N, Beier F, Blasco MA.
  Haematologica 100, 1267-1274.
• Altered telomere homeostasis and resistance to skin carcinogenesis in Suv39h1 transgenic mice.(2015)
  Petti E, Jordi F, Buemi V, Dinami R, Benetti R, Blasco MA, Schoeftner S
  Cell Cycle 14, 1438-1446.
• Impact of chemotherapy on telomere length in sporadic and familial breast cancer patients.(2015)
  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
  Breast Cancer Res Treat 149, 385-394.
• Telomere dynamics in patients with del (5q) MDS before and under treatment with lenalidomide.(2015)
  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
  Leuk Res (in press).
• Profiling of Sox4-dependent transcriptome in skin links tumour suppression and adult stem cell activation(2015)
  Foronda M, Morgado-Palacin L, Gómez-López G, Domínguez O, Pisano DG, Blasco MA
  GENOMICS DATA 6, 21-24.
• Telomerase expression confers cardioprotection in the adult mouse heart after acute myocardial infarction.(2014)
  Bär C, de Jesus BB, Serrano R, Tejera A, Ayuso E, Jimenez V, Formentini I, Bobadilla M, Mizrahi J, de Martino A, Gomez G, Pisano D, Mulero F, Wollert KC, Bosch F, Blasco MA.
  Nat Communications 5, 5863-.
• Destabilization of nucleophosmin mRNA by the HuR/KSRP complex is required for muscle fibre formation.(2014)
  Cammas A, Sanchez BJ, Lian XJ, Dormoy-Raclet V, van der Giessen K, de Silanes IL, Ma J, Wilusz C, Richardson J, Gorospe M, Millevoi S, Giovarelli M, Gherzi R, Di Marco S, Gallouzi IE
  Nat Communications 5, 4190-.
• Identification of TERRA locus unveils a telomere protection role through association to nearly all chromosomes.(2014)
  de Silanes IL, Graña O, De Bonis ML, Dominguez O, Pisano DG, Blasco MA
  Nat Communications 5, 4723-.
• Sox4 links tumor suppression to accelerated aging in mice by modulating stem cell activation.(2014)
  Foronda M, Martínez P, Schoeftner S, Gómez-López G, Schneider R, Flores JM, Pisano DG, Blasco MA
  Cell Reports 8, 487-500.
• In vivo role of checkpoint kinase 2 in signaling telomere dysfunction.(2014)
  García-Beccaria M, Martínez P, Flores JM, Blasco MA
  Aging Cell 13, 810-816.
• Essential role for the TRF2 telomere protein in adult skin homeostasis.(2014)
  Martínez P, Ferrara-Romeo I, Flores JM, Blasco MA
  Aging Cell 13, 656-668.
• SIRT1 is necessary for proficient telomere elongation and genomic stability of induced pluripotent stem cells.(2014)
  De Bonis ML, Ortega S, Blasco MA
  Stem Cell Reports 2, 690-706.
• TopoIIa prevents telomere fragility and formation of ultra thin DNA bridges during mitosis through TRF1-dependent binding to telomeres.(2014)
  d'Alcontres MS, Palacios JA, Mejias D, Blasco MA
  Cell Cycle 13, 1463-1491.
• Genome-wide analysis of in vivo TRF1 binding to chromatin restricts its location exclusively to telomeric repeats.(2014)
  Garrobo I, Marión RM, Domínguez O, Pisano DG, Blasco MA
  Cell Cycle 13, 3742-3749.
• RAP1 protects from obesity through its extratelomeric role regulating gene expression.(2013)
  Martínez P, Gómez-López G, García F, Mercken E, Mitchell S, Flores JM, De Cabo R, Blasco MA
  Cell Reports 3, 2059-2074.
• The hallmarks of aging.(2013)
  López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G
  Cell 153, 1194-1217.
• POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia.(2013)
  Ramsay AJ, Quesada V, Foronda M, Conde L, Martínez-Trillos A, Villamor N, Rodríguez D, Kwarciak A, Garabaya C, Gallardo M, López-Guerra M, López-Guillermo A, Puente XS, Blasco MA, Campo E, López-Otín C
  Nat Genet 45, 526-530.
• p53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes.(2013)
  Mondal AM, Horikawa I, Pine SR, Fujita K, Morgan KM, Vera E, Mazur SJ, Appella E, Vojtesek B, Blasco MA, Lane DP, Harris CC
  J Clin Invest 123, 5247-5257.
• TRF1 is a stem cell marker and is essential for the generation of induced pluripotent stem cells.(2013)
  Schneider RP, Garrobo I, Foronda M, Palacios JA, Marión RM, Flores I, Ortega S, Blasco MA
  Nat Communications 4, 1946-.
• Telomerase at the intersection of cancer and aging.(2013)
  Bernardes de Jesus B, Blasco MA
  Trends Genet 29, 513-520.
• Telomere Length and Telomerase Activity Impact the UV Sensitivity Syndrome Xeroderma Pigmentosum C.(2013)
  Stout GJ, Blasco MA
  Cancer Res 73, 1844-1854.
• Localization-dependent and -independent roles of SLX4 in regulating telomeres.(2013)
  Wilson JS, Tejera AM, Castor D, Toth R, Blasco MA, Rouse J
  Cell Reports 4, 853-860.
• A metabolic signature predicts biological age in mice.(2013)
  Tomás-Loba A, Bernardes de Jesus B, Mato JM, Blasco MA
  Aging Cell 12, 93-101.
• Short telomeres are frequent in hereditary breast tumors and are associated with high tumor grade.(2013)
  Martinez-Delgado B, Gallardo M, Tanic M, Yanowsky K, Inglada-Perez L, Barroso A, Rodriguez-Pinilla M, Cañamero M, Blasco MA, Benitez J
  Breast Cancer Res Treat 141, 231-242.
• Telomerase reverse transcriptase synergizes with calorie restriction to increase health span and extend mouse longevity.(2013)
  Vera E, Bernardes de Jesus B, Foronda M, Flores JM, Blasco MA
  PLoS ONE 8, E53760-.
• Interview: Fighting disease from the chromosome end.(2013)
  Blasco MA
  Epigenomics 5, 483-485.