Research Divisions

Genomics, Cancer and Ageing

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Professor Carlos López Otín

Carlos López Otín is a Professor in the Biochemistry and Molecular Biology department of the Universidad de Oviedo, where he combines teaching work with his research on cancer, the biology of ageing and functional genome analysis.

His work has generated over 400 articles in publications with international-level impact, which have been cited more than 44,000 times and have an aggregated Hirsch index of 100.

He is on the editorial board of a wide range of scientific journals and is a board member of several scientific committees and societies, including the Real Academia de Ciencias Exactas, Físicas y Naturales (Spanish Royal Academy of Sciences ) and the Academia Europæa.

Over the course of his scientific career, he has received several national and international awards and honours, such as honorary PhDs from the Universidad Menéndez Pelayo and Universidad de Zaragoza, the King James I Prize for Basic Research, the FEBS 25th Anniversary Prize in Biochemistry, the Mexican Science and Technology Award and the Santiago Ramón y Cajal National Research Award.

Fernando Bongera s/n, 33006, Oviedo, Spain.

Name Organisation Activity Euraxess classification
Freitas Rodríguez, Sandra Universidad de Oviedo Investigación R2
Gutiérrez Fernández, Ana Universidad de Oviedo Research/Teaching R3
López Otín, Carlos Universidad de Oviedo Research/Teaching R4
Pérez Freije, Jose María Universidad de Oviedo Research/Teaching R3
Quesada Fernández, Víctor Universidad de Oviedo Research/Teaching R3
Rodríguez Arango, Javier Universidad de Oviedo Research/Teaching R1
Rodríguez Folgueras, Alicia Universidad de Oviedo Research R2
Santiago Fernández, Olaya Universidad de Oviedo Research/Teaching R1
Suárez Puente, Xose Antón Universidad de Oviedo Research/Teaching R3
Álvarez Puente, Diana Universidad de Oviedo Research/Teaching No classification
Degradomics

Shortly after joining the Universidad de Oviedo over 30 years ago, Carlos López Otín focused his research efforts on the role of proteolytic systems in pathological processes, including devastating accelerated ageing syndromes. The group he leads has pioneered a holistic approach to research on proteases in health and disease, through innovative concepts such as degradomics and the degradome, along with the development of highly efficient methods for investigating these concepts (in partnership with Chris Overall). In parallel studies, Carlos López Otín’s group has been involved in the functional annotation of the human genome, as well as other genomes and degradomes of evolutionary interest: from chimpanzees and other primates to mice and whales.

Cancer Genomics

Since 2009, Carlos López Otín has been co-director of the Spanish contribution to the International Cancer Genome Consortium’s Chronic Lymphocytic Leukaemia project (ICGC-CLL). As a result of this project, the complete genome sequence of tumours for hundreds of patients with chronic lymphocytic leukaemia has been determined and recurrent mutations in several genes have been identified, which have become key objectives of therapeutic intervention for this common malignancy. The work of Carlos López Otín’s laboratory on molecular oncology has also led to the discovery of several proteases that have paradoxical anti-tumour and anti-metastatic action, as well as two new genes involved in the progression of head and neck carcinomas. In an area that is closely connected to the cancer genome projects, the group has identified the genetic determinants of several hereditary diseases. Highlights of these studies have included the discovery of two new premature ageing syndromes: the Néstor-Guillermo Progeria Syndrome (NGPS) and the Atypical Neonatal Progeroid Syndrome (ANPS). The group’s work has also led to the identification of the genes responsible for hereditary sudden death, microcytic anaemia, bone abnormalities and familial melanoma. These genomic studies are the foundation upon which Carlos López Otín has built a Social Genomics programme. This has enabled the genomic bases of hereditary diseases suffered by families who turn to the laboratory for help, health solutions and knowledge to be studied and, in some cases, revealed.

Ageing

The work of López Otín’s group at the Universidad de Oviedo has also helped to clarify the molecular mechanisms associated with physiological ageing and their links to cancer. The group has published the first comprehensive analysis of key points related to ageing at a molecular and cellular level, and have put forward various strategies for the metabolic control of longevity. Additionally, it has recently developed a method to facilitate the cellular reprogramming of aged human cells into pluripotent cells with embryonic properties. Carlos López Otín’s group has described the loss of the mechanism that regulates proteostasis in myeloid transformation, connecting alterations in haematopoietic stem cells associated with age to the pathogenesis of haematological diseases. Finally, the group has identified the molecular mechanisms underlying various premature ageing syndromes and, in partnership with Nicolas Levy’s group, has developed therapeutic strategies for treating Hutchinson-Gilford Progeria Syndrome (HGPS).

  1. AUTHORS: Ferrando, A. A. and Lopez-Otin, C.
    TITLE: Clonal evolution in leukemia. Nature Med, 23, 1135-1145 (2017).
    de la Rosa, J., Weber, J., Friedrich, M. J., Li, Y., Rad, L., Ponstingl, H., Liang, Q., de Quiros, S. B., Noorani, I., Metzakopian, E., Strong, A., Li, M. A., Astudillo, A., Fernandez-Garcia, M. T., Fernandez-Garcia, M. S., Hoffman, G. J., Fuente, R., Vassiliou, G. S., Rad, R., Lopez-Otin, C., Bradley, A. and Cadinanos, J.
    TITLE: A single-copy Sleeping Beauty transposon mutagenesis screen identifies new PTEN-cooperating tumor suppressor genes. Nature Genet, 49, 730-741 (2017).
  2. AUTHORS: Lopez-Otin, C., Galluzzi, L., Freije, J. M., Madeo, F. and Kroemer, G.
    TITLE: Metabolic Control of Longevity. Cell, 166, 802-21 (2016).
  3. AUTHORS: Osorio, F. G., Soria-Valles, C., Santiago-Fernandez, O., Bernal, T., Mittelbrunn, M., Colado, E., Rodriguez, F., Bonzon-Kulichenko, E., Vazquez, J., Porta-de-la-Riva, M., Ceron, J., Fueyo, A., Li, J., Green, A. R., Freije, J. M. and Lopez-Otin, C.
    TITLE: Loss of the proteostasis factor AIRAPL causes myeloid transformation by deregulating IGF-1 signaling. Nature Med, 22, 91-6 (2016).
  4. AUTHORS: Puente, X. S., et al.
    TITLE: Non-coding recurrent mutations in chronic lymphocytic leukaemia. Nature, 526, 519-24 (2015).
  5. AUTHORS: Soria-Valles, C., Osorio, F. G., Gutierrez-Fernandez, A., De Los Angeles, A., Bueno, C., Menendez, P., Martin-Subero, J. I., Daley, G. Q., Freije, J. M. and Lopez-Otin, C.
    TITLE: NF-kappaB activation impairs somatic cell reprogramming in ageing. Nature Cell Biol, 17, 1004-13 (2015).
  6. AUTHORS: Quiros, P. M., Langer, T. and Lopez-Otin, C.
    TITLE: New roles for mitochondrial proteases in health, ageing and disease. Nature Rev Mol Cell Biol, 16, 345-59 (2015).
  7. AUTHORS: Robles-Espinoza, C. D.,et al.
    TITLE: POT1 loss-of-function variants predispose to familial melanoma. Nature Genet, 46, 478-81 (2014).
  8. AUTHORS: Gordon, L. B., Rothman, F. G., Lopez-Otin, C. and Misteli, T.
    TITLE: Progeria: a paradigm for translational medicine. Cell, 156, 400-7 (2014).
  9. AUTHORS:
    TITLE: Marmoset Genome Sequencing and Analysis Consortium. The common marmoset genome provides insight into primate biology and evolution. Nature Genet, 46, 850-7 (2014).
  10. AUTHORS: Fanjul-Fernandez, M., Quesada, V., Cabanillas, R., Cadinanos, J., Fontanil, T., Obaya, A., Ramsay, A. J., Llorente, J. L., Astudillo, A., Cal, S. and Lopez-Otin, C.
    TITLE: Cell-cell adhesion genes CTNNA2 and CTNNA3 are tumour suppressors frequently mutated in laryngeal carcinomas. Nature Commun, 4, 2531 (2013).
  11. AUTHORS: Alexandrov, L. B., et al.
    TITLE: Signatures of mutational processes in human cancer. Nature, 500, 415-21 (2013).
  12. AUTORES: de la Rosa, J., Freije, J. M., Cabanillas, R., Osorio, F. G., Fraga, M. F., Fernandez-Garcia, M. S., Rad, R., Fanjul, V., Ugalde, A. P., Liang, Q., Prosser, H. M., Bradley, A., Cadinanos, J. and Lopez-Otin, C.
    TITLE: Prelamin A causes progeria through cell-extrinsic mechanisms and prevents cancer invasion. Nature Commun, 4, 2268 (2013).
  13. AUTHORS: Lapuente-Brun, E., Moreno-Loshuertos, R., Acin-Perez, R., Latorre-Pellicer, A., Colas, C., Balsa, E., Perales-Clemente, E., Quiros, P. M., Calvo, E., Rodriguez-Hernandez, M. A., Navas, P., Cruz, R., Carracedo, A., Lopez-Otin, C., Perez-Martos, A., Fernandez-Silva, P., Fernandez-Vizarra, E. and Enriquez, J. A.
    TITLE: Supercomplex assembly determines electron flux in the mitochondrial electron transport chain. Science, 340, 1567-70 (2013).
  14. AUTHORS: Lopez-Otin, C., Blasco, M. A., Partridge, L., Serrano, M. and Kroemer, G.
    TITLE: The hallmarks of aging. Cell, 153, 1194-217 (2013).
  15. AUTHORS: Ramsay, A. J., Quesada, V., Foronda, M., Conde, L., Martinez-Trillos, A., Villamor, N., Rodriguez, D., Kwarciak, A., Garabaya, C., Gallardo, M., Lopez-Guerra, M., Lopez-Guillermo, A., Puente, X. S., Blasco, M. A., Campo, E. and Lopez-Otin, C.
    TITLE: POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia. Nature Genet, 45, 526-30 (2013).
  16. AUTHORS: Puente, X. S. and Lopez-Otin, C.
    TITLE: The evolutionary biography of chronic lymphocytic leukemia. Nature Genet, 45, 229-31 (2013).
  17. AUTHORS: Quesada, V., et al.
    TITLE: Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nature Genet, 44, 47-52 (2012).
  18. AUTHORS: Puente, X. S., et al.
    TITLE: Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature, 475, 101-5 (2011).
  19. AUTHORS: Puente, X. S., Quesada, V., Osorio, F. G., Cabanillas, R., Cadinanos, J., Fraile, J. M., Ordonez, G. R., Puente, D. A., Gutierrez-Fernandez, A., Fanjul-Fernandez, M., Levy, N., Freije, J. M. and Lopez-Otin, C.
    TITLE: Exome sequencing and functional analysis identifies BANF1 mutation as the cause of a hereditary progeroid syndrome. Am J Hum Genet, 88, 650-6 (2011).
  20. AUTHORS: Locke, D. P., et al.
    TITLE: Comparative and demographic analysis of orang-utan genomes. Nature, 469, 529-33 (2011).
  21. AUTHORS: Warren, W. C., et al.
    TITLE: The genome of a songbird. Nature, 464, 757-62 (2010).
  22. AUTHORS: Lopez-Otin, C. and Hunter, T.
    TITLE: The regulatory crosstalk between kinases and proteases in cancer. Nature Rev Cancer, 10, 278-92 (2010).
  23. AUTHORS:
    TITLE: International Cancer Genome Consortium. International network of cancer genome projects. Nature, 464, 993-8 (2010).
  24. AUTHORS: Quesada, V., Ordonez, G. R., Sanchez, L. M., Puente, X. S. and Lopez-Otin, C.
    TITLE: The Degradome database: mammalian proteases and diseases of proteolysis. Nucleic Acids Res, 37, D239-43 (2009).
  25. AUTHORS: Varela, I., Pereira, S., Ugalde, A. P., Navarro, C. L., Suarez, M. F., Cau, P., Cadinanos, J., Osorio, F. G., Foray, N., Cobo, J., de Carlos, F., Levy, N., Freije, J. M. and Lopez-Otin, C.
    TITLE: Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging. Nature Med, 14, 767-72 (2008).
  26. AUTHORS: Warren, W. C., et al.
    TITLE: Genome analysis of the platypus reveals unique signatures of evolution. Nature, 453, 175-83 (2008).
  27. AUTHORS: Espada, J., Varela, I., Flores, I., Ugalde, A. P., Cadinanos, J., Pendas, A. M., Stewart, C. L., Tryggvason, K., Blasco, M. A., Freije, J. M. and Lopez-Otin, C.
    TITLE: Nuclear envelope defects cause stem cell dysfunction in premature-aging mice. J Cell Biol, 181, 27-35 (2008).
  28. AUTHORS: Lopez-Otin, C. and Bond, J. S.
    TITLE: Proteases: multifunctional enzymes in life and disease. J Biol Chem, 283, 30433-7 (2008).
  29. AUTHORS: Lopez-Otin, C. and Matrisian, L. M.
    TITLE: Emerging roles of proteases in tumour suppression. Nature Rev Cancer, 7, 800-8 (2007).
  30. AUTHORS: Marino, G., Salvador-Montoliu, N., Fueyo, A., Knecht, E., Mizushima, N. and Lopez-Otin, C.
    TITLE: Tissue-specific autophagy alterations and increased tumorigenesis in mice deficient in Atg4C/autophagin-3. J Biol Chem, 282, 18573-83 (2007).
  31. AUTHORS: Liu, B., Wang, J., Chan, K. M., Tjia, W. M., Deng, W., Guan, X., Huang, J. D., Li, K. M., Chau, P. Y., Chen, D. J., Pei, D., Pendas, A. M., Cadinanos, J., Lopez-Otin, C., Tse, H. F., Hutchison, C., Chen, J., Cao, Y., Cheah, K. S., Tryggvason, K. and Zhou, Z.
    TITLE: Genomic instability in laminopathy-based premature aging. Nature Med, 11, 780-5 (2005).
  32. AUTHORS:
    TITLE: Chimpanzee Sequencing and Analysis Consortium. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature, 437, 69-87 (2005).
  33. AUTHORS:
    TITLE: Rat Genome Sequencing Project Consortium. Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature, 428, 493-521 (2004).
  34. AUTHORS: Balbin, M., Fueyo, A., Tester, A. M., Pendas, A. M., Pitiot, A. S., Astudillo, A., Overall, C. M., Shapiro, S. D. and Lopez-Otin, C.
    TITLE: Loss of collagenase-2 confers increased skin tumor susceptibility to male mice. Nature Genet, 35, 252-7 (2003).
  35. AUTHORS: Puente, X. S., Sanchez, L. M., Overall, C. M. and Lopez-Otin, C.
    TITLE: Human and mouse proteases: a comparative genomic approach. Nature Rev Genet, 4, 544-58 (2003).
  36. AUTHORS: Cal, S., Quesada, V., Garabaya, C. and Lopez-Otin, C.
    TITLE: Polyserase-I, a human polyprotease with the ability to generate independent serine protease domains from a single translation product. Proc Natl Acad Sci U S A, 100, 9185-90 (2003).
  37. AUTHORS: Pendas, A. M., Zhou, Z., Cadinanos, J., Freije, J. M., Wang, J., Hultenby, K., Astudillo, A., Wernerson, A., Rodriguez, F., Tryggvason, K. and Lopez-Otin, C.
    TITLE: Defective prelamin A processing and muscular and adipocyte alterations in Zmpste24 metalloproteinase-deficient mice. Nature Genet, 31, 94-9 (2002).
  38. AUTHORS: Lopez-Otin, C. and Overall, C. M.
    TITLE: Protease degradomics: a new challenge for proteomics. Nature Rev Mol Cell Biol, 3, 509-19 (2002).
  39. AUTHORS: Overall, C. M. and Lopez-Otin, C.
    TITLE: Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nature Rev Cancer, 2, 657-72 (2002).
  40. AUTHORS: Freije, J. M., Diez-Itza, I., Balbin, M., Sanchez, L. M., Blasco, R., Tolivia, J. and Lopez-Otin, C.
    TITLE: Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas. J Biol Chem, 269, 16766-73 (1994).