Grupo de Telómeros y Telomerasa - Fundación Humanismo y Ciencia

María A. Blasco Jefe de Grupo
T +34 917328032 (Ext 3400)
mblasco@cnio.es

Investigadores

Becarios Post-doctorales

Giuseppe Bosso
María Isabel Espejo
Buyun Ma
Arpita Saha
Sarita Saraswati

Becarios Pre-Doctorales

José Carlos González
Óscar Laguía
Jessica Louzame
Amparo Sánchez
Raúl Sánchez

Técnicos de Laboratorio

David Hernández
Rosa María Serrano

Immortality is one of the most universal characteristics of cancer cells. We study the mechanisms by which tumour cells are immortal and normal cells are mortal. 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 age-related diseases.
Interplay between telomeres and DNA repair pathways.
Role and regulation of non-coding telomeric RNAs or TERRA.
Testing telomerase gene therapy in telomere syndromes and age-related diseases.
Role of telomerase and telomeres in adult stem cell biology and in nuclear reprogramming of differentiated cells to iPS cells.

Publicaciones

López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (2023). Hallmarks of aging: An expanding universe. Cell 186, 243-278. Publicación CNIO.
Ayora M, Fraguas D, Abregú-Crespo R, Recio S, Blasco MA, Moises A, Derevyanko A, Arango C, Díaz-Caneja CM. (2022). Leukocyte telomere length in patients with schizophrenia and related disorders: a meta-analysis of case-control studies. Mol Psychiatr 27, 2968-2975. Publicación CNIO.
Piñeiro-Hermida S, Martínez P, Bosso G, Flores JM, Saraswati S, Connor J, Lemaire R, Blasco MA (2022). Consequences of telomere dysfunction in fibroblasts, club and basal cells for lung fibrosis development. Nat Commun 13, 5656. Publicación CNIO. Open Access
Sanz-Ros J, Romero-García N, Mas-Bargues C, Monleón D, Gordevicius J, Brooke RT, Dromant M, Díaz A, Derevyanko A, Guío-Carrión A, Román-Domínguez A, Inglés M, Blasco MA, Horvath S, Viña J, Borrás C (2022). Small extracellular vesicles from young adipose-derived stem cells prevent frailty, improve health span, and decrease epigenetic age in old mice. Sci Adv 8, eabq2226. Publicación CNIO.
Montero-Conde C, Leandro-García LJ, Martínez-Montes ÁM, Martínez P, Moya FJ, Letón R, Gil E, Martínez-Puente N, Guadalix S, Currás-Freixes M, García-Tobar L, Zafon C, Jordà M, Riesco-Eizaguirre G, González-García P, Monteagudo M, Torres-Pérez R, Mancikova V, Ruiz-Llorente S, Pérez-Martínez M, Pita G, Galofré JC, Gonzalez-Neira A, Cascón A, Rodríguez-Antona C, Megías D, Blasco MA, Caleiras E, Rodríguez-Perales S, Robledo M (2022). Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers. Clin Transl Med 12, e1001. Publicación CNIO.
Bosso G, Lanuza-Gracia P, Piñeiro-Hermida S, Yilmaz M, Serrano R, Blasco MA (2022). Early differential responses elicited by BRAFV600E in adult mouse models.. Cell Death Dis 13, 142. Publicación CNIO.
Martínez P, Sánchez-Vázquez R, Ferrara-Romeo I, Serrano R, Flores JM, Blasco MA (2022). A mouse model for Li-Fraumeni-Like Syndrome with cardiac angiosarcomas associated to POT1 mutations. Plos Genetics 18, e1010260. Publicación CNIO.
Martínez P, Blasco MA (2021). An enzyme to cure age-related diseases. Nat Catal 4, 738-739. Publicación CNIO.
Piñeiro-Hermida S, Martínez P, Blasco MA (2021). Short and dysfunctional telomeres protect from allergen-induced airway inflammation. Aging Cell 20, e13352. Publicación CNIO.
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. Publicación CNIO.
Bacalini MG, Reale A, Malavolta M, Ciccarone F, Moreno-Villanueva M, Dollé MET, Jansen E, Grune T, Gonos ES, Schön C, Bernhardt J, Grubeck-Loebenstein B, Sikora E, Toussaint O, Debacq-Chainiaux F, Capri M, Hervonen A, Hurme M, Slagboom PE, Breusing N, Aversano V, Tagliatesta S, Franceschi C, Blasco MA, Bürkle A, Caiafa P, Zampieri M (2021). Ageing affects subtelomeric DNA methylation in blood cells from a large European population enrolled in the MARK-AGE study.. Geroscience 43, 1283-1302. Publicación CNIO.
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 39, 866-881. Publicación CNIO.
Monteagudo M, Martínez P, Leandro-García LJ, Martínez-Montes ÁM, Calsina B, Pulgarín-Alfaro M, Díaz-Talavera A, Mellid S, Letón R, Gil E, Pérez-Martínez M, Megías D, Torres-Ruiz R, Rodriguez-Perales S, González P, Caleiras E, Jiménez-Villa S, Roncador G, Álvarez-Escolá C, Regojo RM, Calatayud M, Guadalix S, Currás-Freixes M, Rapizzi E, Canu L, Nölting S, Remde H, Fassnacht M, Bechmann N, Eisenhofer G, Mannelli M, Beuschlein F, Quinkler M, Rodríguez-Antona C, Cascón A, Blasco MA, Montero-Conde C, Robledo M (2021). Analysis of Telomere Maintenance Related Genes Reveals NOP10 as a New Metastatic-Risk Marker in Pheochromocytoma/Paraganglioma. Cancers 13, 4758. Publicación CNIO.
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. Publicación CNIO.
Sánchez-Vázquez R, Martínez P, Blasco MA (2021). AKT-dependent signaling of extracellular cues through telomeres impact on tumorigenesis. Plos Genetics 17, e1009410. Publicación CNIO.
Saraswati S, Martinez P, Graña-Castro O, Blasco MA (2021). Short and dysfunctional telomeres sensitize the kidneys to develop fibrosis.. Nature Aging 1, 269-283. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO. Open Access
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. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO.
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.. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO. 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. Publicación CNIO.
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). Publicación CNIO.
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. Publicación CNIO. Open Access
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. Publicación CNIO.
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. Publicación CNIO. 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. Publicación CNIO. 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. Publicación CNIO.
Montero-Conde C, Graña-Castro O, Martín-Serrano G, Martínez-Montes ÁM, Zarzuela E, Muñoz J, Torres-Perez R, Pita G, Cordero-Barreal A, Leandro-García LJ, Letón R, de Silanes IL, Guadalix S, Pérez-Barrios A, Hawkins F, Guerrero-Álvarez A, Álvarez-Escolá C, Regojo-Zapata R, Calsina B, Remacha L, Roldán-Romero JM, Santos M, Lanillos J, Jordá M, Riesco-Eizaguirre G, Zafon C, González-Neira A, Blasco MA, Al-Shahrour F, Rodríguez-Antona C, Cascón A, Robledo M. (2019). Hsa-miR-139-5p is a prognostic thyroid cancer marker involved in HNRNPF-mediated alternative splicing.. Int J Cancer 146, 521-530. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO. Open Access
Martínez P, Blasco MA (2018). Heart-Breaking Telomeres. Circ Res 123, 787-802. Publicación CNIO.
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. Publicación CNIO. Open Access
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. Publicación CNIO. 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. Publicación CNIO. Open Access
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. Publicación CNIO. 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. Publicación CNIO. Open Access