María A. Blasco

María A. Blasco, investigadora del programa de ciencia de la Fundación Botín

Telomeres and Telomerase Group - Molecular Oncology Programme

Centro Nacional de Investigaciones Oncologicas (CNIO)

Madrid, Spain

Maria A. Blasco obtained her PhD in 1993 for research on DNA polymerases at the Centro de Biología Molecular 'Severo Ochoa' under the supervision of M. Salas. That same year, Blasco joined the Cold Spring Harbor Laboratory, New York, USA, as a Postdoctoral Fellow under the leadership of C. W. Greider.

In 1997 she returned to Spain to start her own research Group at the Centro Nacional de Biotecnología in Madrid, where she continued her work on the development of mouse models for the study of the role of telomerase in cancer and ageing.

She joined the CNIO in 2003 as Director of the Molecular Oncology Programme and Leader of the Telomeres and Telomerase Group. In 2005 she was appointed CNIO Vice Director.

Maria Blasco has made fundamental contributions in the field of telomerase and the role they play in cancer and ageing:

She generated the first knock-out mouse for telomerase demonstrating that: telomerase was the only one enzyme in mammals responsible for the generation of telomeres, short telomeres in the absence of telomerase act as potent tumours suppressors, telomere shortening resulted in chromosome instability, aging-associated pathologies and reduced lifespan.

She generated the first transgenic mouse with increased telomerase expression in adult tissues, uncovering a role for telomerase in promoting tumorigenesis.

She connected DNA damage repair to telomere function.

She demonstrated for the first time that both telomerase activity and telomere length are determinant for the tissue renewal capacity of adult stem cells.

She found that telomerase over-expression in the context of cancer-resistant mice improves organismal fitness, produces a systemic delay in ageing and an extension of the median life span, demonstrating for the first time in any organism the anti-aging effects of telomerase.

She discovered that telomerase is needed in the starting cells for effective generation of induced Pluripotent Stem Cells (iPSs), telomeres rejuvenate to levels identical to those of embryonic stem cells after reprogramming.

She identified the molecular mechanisms by which short telomeres or any other kind of DNA damage limit nuclear reprogramming, p53 prevents nuclear reprogramming of defective cells acting as a quality control barrier during the reprogramming process.

She discovered that the telomeric protein TRF1 is responsible for premature ageing and increased cancer risk in mice, providing the demonstration for the first time ever that a telomeric protein can act both as a tumour suppressor and as an ageing-preventing factor.

Blasco has received the Swiss Bridge Award for Research in Cancer, the Josef Steiner Cancer Research Award, the EMBO Gold Medal, the Fundación Carmen and Severo Ochoa Award for Molecular Biology, the Rey Jaime I Basic Research Award, the Körber European Science Award, the Alberto Sols Biomedical Research Award, the Fundación Lilly 2010 Award in Preclinical Biomedical Research, and the Santiago Ramón y Cajal National Research Award 2010 in Biology. She also serves on the Editorial Board of several scientific journals, she is a Member of the Academia Europaea, she is also an elected EMBO Member sitting at the EMBO Council since 2008.

Research interest:

  • The group studies the mechanisms by which tumour cells are immortal (unlimited divisions) while normal cells are mortal (limited divisions). The immortality of the cancer cells is one of their most universal characteristics. The enzyme telomerase is present in more than 95% of all types of human cancers and non-present in the normal cells of the organism. Telomeres are nucleoprotein complexes at the ends of chromosomes that are essential for chromosome protection and genomic stability. One of the many factors leading to ageing is the progressive shortening of telomeres associated to organismal ageing. When telomeres are altered (in their length or their integrity) the adult stem cells have a maimed regenerative capacity.
  • Telomere length defects, therefore, are associated to cancer and ageing processes and have a profound effect on stem cell behaviour. The group aims to determine the role of genetic and epigenetic telomere regulators in cancer and ageing by generating new mouse models and studying the role of these factors in stem cell biology.
    Study the biology of telomeres and telomerase: generation of mouse models to study the role of telomeres and telomerase in cancer and ageing
  • Assess the interplay between telomeres and DNA repair pathways
  • Characterise telomeric heterochromatin
  • Elucidate the role of telomerase and telomeres in adult stem cell biology and in nuclear reprogramming of differentiated cells to induced Pluripotent Stem (iPS) cells.

Most relevant publications:

  • Martínez, P., Thanasoula, M., Carlos, AR., Gómez-López, G., Tejera, AM., Schoeftner, S., Dominguez, O., Pisano, DG., Tarsounas, M., Blasco, MA. Mammalian Rap1 controls telomere function and gene expression through binding to telomeric and extratelomeric sites. Nat Cell Biol. 12, 768-780 (2010).
  • Martínez, P., Blasco, MA. Role of shelterin in cancer and aging. Aging Cell. [Epub ahead of print] Doi: 10.1111/j.1474-9726.2010.00596.x. (2010).
  • Tejera, AM., Stagno d'Alcontres, M., Thanasoula, M., Marión, RM., Martínez, P., Liao, C., Flores, JM., Tarsounas, M., Blasco, MA. TPP1 is required for TERT recruitment, telomere elongation during nuclear reprogramming, and normal skin development in mice. Dev. Cell, 18, 775-789 (2010).
  • Schoeftner, .S, Blanco, R., López de Silanes, I., Muñoz, P., Gómez-López, G., Flores, JM., Blasco, MA. Telomere shortening relaxes X chromosome inactivation and forces global transcriptome alterations. Proc Natl Acad Sci U S A. 106, 19393-19398 (2009).
  • Schoeftner, S., Blasco, MA. Chromatin regulation and non-coding RNAs at mammalian telomeres. Semin. Cell Dev. Biol. 21, 186-193 (2009).
  • Martínez, P., Thanasoula, M., Muñoz, P., Liao, C., Tejera, A., McNees, C., Flores, JM., Fernández-Capetillo, O., Tarsounas, M., Blasco, MA. Increased telomere fragility and fusions resulting from TRF1 deficiency lead to degenerative pathologies and increased cancer in mice. Genes Dev. 23, 2060-2075 (2009)
  • Marión, RM., Strati, K., Li, H., Murga, M., Blanco, R., Ortega, S., Fernandez-Capetillo, O., Serrano, M., Blasco, MA. A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature, 460, 1149-1153 (2009)
  • Marion, RM., Strati, K., Li, H., Schoeftner, S., Tejera, A., Serrano, M. and Blasco, MA. Telomeres in induced pluripotent stem (iPS) cells acquire ES cells characteristics. Cell Stem Cell, 4, 141-154 (2009)
  • Tomás, A., Flores, I., Fernandez-Marcos, P., Cayuela, ML, Maraver, A., Tejera, A., Borras, C., Matheu, A., Klatt, P., Flores, JM., Viña, J., Serrano, M., and Blasco, MA. Telomerase reverse transcriptase delays aging in cancer resistant mice. Cell, 135, 609-622 (2008)
  • Schoeftner, S., and Blasco, MA. Developmentally regulated transcription of mamalian telomeres by DNA dependent RNA polymerase II. Nat. Cell Biol. 10, 228-236 (2008).

 

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