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Dr. Oscar Fernandez-Capetillo - Nucleolar stress as a driver of cancer (and a vulnerability)

 

Oscar Fernandez-Capetillo

Spanish National Cancer Research Centre (CNIO), Madrid, Spain

Nucleolar stress as a driver of cancer (and a vulnerability)

Alterations in nucleoli have been associated to cancer since the earliest microscopic studies on cancer samples. In addition, mutations in proteins associated to nucleoli and/or ribosome production are often found associated with an increase incidence on cancer. Still, how nucleolar stress drives carcinogenesis and how can this be exploited therapeutically remains rudimentarily understood. During the talk I will present a series of mouse models, genetic and chemical screens related to the role of nucleolar stress in cancer (and also somewhat to neurodegeneration), which are helping us to obtain a better understanding of this emergent field.

Selected references

  • Olbrich T, Vega-Sendino M, Murga M, de Carcer G, Malumbres M, Ortega S, Ruiz S, Fernandez-Capetillo O. A chemical screen identifies compounds capable of selecting for haploidy in mammalian cells. Cell Rep 2019 28(3):597-604.e4
  • Corman A, Jung B, Häggblad M, Bräutigam L, Lafarga V, Lidemalm L, Hühn D, Carreras-Puigvert J, Fernandez-Capetillo O. A chemical screen identifies compounds limiting the toxicity of C9ORF72 dipeptide repeats. Cell Chem Biol 2019 26(2):235-243.e5
  • Olbrich T, Mayor-Ruiz C, Vega-Sendino M, Gomez C, Ortega S, Ruiz S, Fernandez-Capetillo O. A p53-dependent response limits the viability of mammalian haploid cells. Proc Natl Acad Sci USA 2017 114(35):9367-9372
  • Morgado-Palacin I, Day A, Murga M, Lafarga V, Anton ME, Tubbs A, Chen HT, Ergan A, Anderson R, Bhandoola A, Pike KG, Barlaam B, Cadogan E, Wang X, Pierce AJ, Hubbard C, Armstrong SA, Nussenzweig A, Fernandez-Capetillo O. Targeting the kinase activities of ATR and ATM exhibits antitumoral activity in mouse models of MLL-rearranged AML. Sci Signal 2016 9(445):ra91
  • Murga M, Lecona E, Kamileri I, Díaz M, Lugli N, Sotiriou SK, Anton ME, Méndez J, Halazonetis TD, Fernandez-Capetillo O. POLD3 is haploinsufficient for DNA replication in mice. Mol Cell 2016 63(5):877-83
  • Ruiz S, Mayor-Ruiz C, Lafarga V, Murga M, Vega-Sendino M, Ortega S, Fernandez-Capetillo O. A genome-wide CRISPR screen identifies CDC25A as a determinant of sensitivity to ATR inhibitors. Mol Cell 2016 62(2):307-313
  • Lecona E, Rodriguez-Acebes S, Specks J, Lopez-Contreras AJ, Ruppen I, Murga M, Muñoz J, Mendez J, Fernandez-Capetillo O. USP7 is a SUMO deubiquitinase essential for DNA replication. Nat Struct Mol Biol 2016 23(4):270-7

Contact: Sébastien Britton (Sebastien.Britton@ipbs.fr)

Link to attend the seminar: https://meet.starleaf.com/4198351294/app

21 Sep

11:00 - 12:00

Online seminar