Telomeres and Telomerase Group

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

Staff Scientists

Post-Doctoral Fellows

Giuseppe Bosso
Sergio Piñeiro
Sarita Saraswati
Kurt Whittemore

Graduate Students

José Carlos González
Jessica Louzame
Juan José Montero
Raúl Sánchez

Technicians

Ana Guío
Rosa María Serrano

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 is absent in normal cells in the body. Telomeres are nucleoprotein complexes located at the ends of chromosomes and are 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

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.
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 (in press).
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.
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.
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.
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.
Martínez P, Blasco MA (2018). Heart-Breaking Telomeres. Circ Res 123, 787-802.
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.
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.
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.
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.
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.
Marión RM, Blasco MA (2017). Long Live Partial Reprogramming.. Circ Res 120, 1381-1383.
Martínez P, Blasco MA. (2017). Telomere-driven diseases and telomere-targeting therapies.. J Cell Biol 216, 875-887.
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.
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.
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.
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.
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.
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..
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.
Montero JJ, López de Silanes I, Graña O, Blasco MA (2016). Telomeric RNAs are essential to maintain telomeres.. Nat Communications 7, 12534.
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 Communications 7, 11739.
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.
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 (in press).
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.
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.
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.
Bär C, Blasco MA (2016). Telomeres and telomerase as therapeutic targets to prevent and treat age-related diseases.. F1000Res 20, 5.
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.
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.
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 Communications 6, 8383.
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 Communications 6, 8487.
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 Communications 6, 8036.
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 Communications 6, 7631.
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 Communications 6, 7505.
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.
Martínez P, Blasco MA (2015). Replicating through telomeres: a means to an end.. Trends Biochem Sci 40, 504-515.
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.
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.
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.
Povedano JM, Martinez P, Flores JM, Mulero F, Blasco MA (2015). Mice with Pulmonary Fibrosis Driven by Telomere Dysfunction.. Cell Reports 12, 286-299.
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.
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.
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.
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).
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.
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. (2014). Telomerase expression confers cardioprotection in the adult mouse heart after acute myocardial infarction.. Nat Communications 5, 5863.
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 (2014). Destabilization of nucleophosmin mRNA by the HuR/KSRP complex is required for muscle fibre formation.. Nat Communications 5, 4190.
de Silanes IL, Graña O, De Bonis ML, Dominguez O, Pisano DG, Blasco MA (2014). Identification of TERRA locus unveils a telomere protection role through association to nearly all chromosomes.. Nat Communications 5, 4723.
Foronda M, Martínez P, Schoeftner S, Gómez-López G, Schneider R, Flores JM, Pisano DG, Blasco MA (2014). Sox4 links tumor suppression to accelerated aging in mice by modulating stem cell activation.. Cell Reports 8, 487-500.
García-Beccaria M, Martínez P, Flores JM, Blasco MA (2014). In vivo role of checkpoint kinase 2 in signaling telomere dysfunction.. Aging Cell 13, 810-816.
Martínez P, Ferrara-Romeo I, Flores JM, Blasco MA (2014). Essential role for the TRF2 telomere protein in adult skin homeostasis.. Aging Cell 13, 656-668.
De Bonis ML, Ortega S, Blasco MA (2014). SIRT1 is necessary for proficient telomere elongation and genomic stability of induced pluripotent stem cells.. Stem Cell Reports 2, 690-706.
d'Alcontres MS, Palacios JA, Mejias D, Blasco MA (2014). TopoIIa prevents telomere fragility and formation of ultra thin DNA bridges during mitosis through TRF1-dependent binding to telomeres.. Cell Cycle 13, 1463-1491.
Garrobo I, Marión RM, Domínguez O, Pisano DG, Blasco MA (2014). Genome-wide analysis of in vivo TRF1 binding to chromatin restricts its location exclusively to telomeric repeats.. Cell Cycle 13, 3742-3749.
Martínez P, Gómez-López G, García F, Mercken E, Mitchell S, Flores JM, De Cabo R, Blasco MA (2013). RAP1 protects from obesity through its extratelomeric role regulating gene expression.. Cell Reports 3, 2059-2074.
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013). The hallmarks of aging.. Cell 153, 1194-1217.
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 (2013). POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia.. Nat Genet 45, 526-530.
Mondal AM, Horikawa I, Pine SR, Fujita K, Morgan KM, Vera E, Mazur SJ, Appella E, Vojtesek B, Blasco MA, Lane DP, Harris CC (2013). p53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes.. J Clin Invest 123, 5247-5257.
Schneider RP, Garrobo I, Foronda M, Palacios JA, Marión RM, Flores I, Ortega S, Blasco MA (2013). TRF1 is a stem cell marker and is essential for the generation of induced pluripotent stem cells.. Nat Communications 4, 1946.
Bernardes de Jesus B, Blasco MA (2013). Telomerase at the intersection of cancer and aging.. Trends Genet 29, 513-520.
Stout GJ, Blasco MA (2013). Telomere Length and Telomerase Activity Impact the UV Sensitivity Syndrome Xeroderma Pigmentosum C.. Cancer Res 73, 1844-1854.
Wilson JS, Tejera AM, Castor D, Toth R, Blasco MA, Rouse J (2013). Localization-dependent and -independent roles of SLX4 in regulating telomeres.. Cell Reports 4, 853-860.
Tomás-Loba A, Bernardes de Jesus B, Mato JM, Blasco MA (2013). A metabolic signature predicts biological age in mice.. Aging Cell 12, 93-101.
Martinez-Delgado B, Gallardo M, Tanic M, Yanowsky K, Inglada-Perez L, Barroso A, Rodriguez-Pinilla M, Cañamero M, Blasco MA, Benitez J (2013). Short telomeres are frequent in hereditary breast tumors and are associated with high tumor grade.. Breast Cancer Res Treat 141, 231-242.
Vera E, Bernardes de Jesus B, Foronda M, Flores JM, Blasco MA (2013). Telomerase reverse transcriptase synergizes with calorie restriction to increase health span and extend mouse longevity.. PLoS ONE 8, E53760.
Blasco MA (2013). Interview: Fighting disease from the chromosome end.. Epigenomics 5, 483-485.