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.
Publications
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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. CNIO Publication.
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. CNIO Publication.
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. 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.
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.
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. 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.
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