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Azzalin, Claus M

Telomeres, long noncoding RNAs and genome stability

Telomeres are heterochromatic nucleoprotein structures 'capping' the very end of linear eukaryotic chromosomes. Telomeres are essential to protect chromosome ends and to impose a finite lifespan to cells and tissues. Dysfunctional telomeres cause severe chromosome instability, thereby unleashing cascades of cellular reactions that are common hallmarks of human diseases such as cancer and premature aging.

We employ molecular biology, cell biology and biochemistry to understand how telomeres execute their protective functions and how telomeric dysfunctions are mechanistically linked to pathological conditions. In particular, we study how the telomeric long noncoding RNA TERRA participates in maintaining proper telomere structure and functions in both normal and diseased human cells.

We are currently exploring how TERRA supports telomere elongation in cancer cells either by promoting activity of the specialized reverse transcriptase telomerase or by triggering homologous recombination-mediated synthesis of telomeric DNA. We are also investigating the consequences of perturbing TERRA transcription and localization on telomere integrity and cellular physiology.

  • Research Areas

    • Cell Biology, Molecular Biology and Biochemistry.
    • Telomeres and TERRA Chromatin and long noncoding
    • RNA Genome stability
    • Cancer
    • Aging
  • Research Team

    • Ongoing Research Projects

      2018/2021 Telomeric R-loop-mediated recombination in the alternative lengthening of telomeres pathway: towards designing novel therapeutic avenues for cancer therapy - FCT Research Grant (PTDC/MED-ONC/28282/2017). Coordinators: Bruno Silva and Claus M. Azzalin.

      2018/2021 TERRA and telomerase-mediated telomere elongation: unveiling novel molecular pathways towards the development of innovative therapeutic approaches for cancer treatment - FCT Research Grant (PTDC/BIA-MOL/29352/2017). Coordinator: Claus M. Azzalin.

      2017/2019 TERRA and telomere transcription: towards therapies for healthy aging - EMBO Installation Grant (IG 3576). Coordinator: Claus M. Azzalin.

      2016/2021 TERRA and telomere transcription at the crossroads of cancer and aging - FCT Investigator Programme Grant (IF/01269/2015). Coordinator: Claus M. Azzalin.

      2015/2018 The multiple roles of TERRA in telomere length maintenance, telomere integrity, cancer and cellular senescence - Swiss National Science Foundation (31003A_160338). Coordinator: Claus M. Azzalin.

    • Prizes

      2017 EMBO Installation Grant award to Claus M. Azzalin

      2016 FCT Investigator Award to Claus M. Azzalin

      2016 Best Poster Prize at the EMBO conference 'Telomeres, telomerase and disease' (Liege, Belgium) to Yong Woo Lee

      2014 Nomination to the Editorial Board of FEBS Letters to Claus M. Azzalin

      2013 Associate Membership of Epigenesys, a FP7 European Community-funded Network of Excellence to Claus M. Azzalin

      2012 EMBO Young Investigator Award to Claus M. Azzalin

      2009 Swiss National Science Foundation Professorship to Claus M. Azzalin

    • Selected Publications

      • Lee YW, Arora R, Wischnewski H, Azzalin CM (2018) TRF1 participates in chromosome end protection by averting TRF2-dependent telomeric R loops. Nat Struct Mol Biol; 25: 147-153.
      • Zanini IM, Soneson C, Lorenzi LE, Azzalin CM (2017) Human Cactin interacts with DHX8 and SRRM2 to assure efficient pre-mRNA splicing and sister chromatid cohesion. J Cell Sci; 130: 767-778.
      • Moravec M, Wischnewski H, Bah A, Hu Y, Liu N, Lafranchi L, King MC, Azzalin CM (2016) TERRA promotes telomerase-mediated telomere elongation in Schizosaccharomyces pombe. EMBO Rep; 17:999-1012.
      • Lorenzi LE, Bah A, Wischnewski H, Shchepachev V, Soneson C, Santagostino M, Azzalin CM (2014) Fission yeast Cactin restricts telomere transcription and elongation by regulating Rap1 levels. EMBO J; 34:115-129.
      • Arora R, Lee YW, Wischnewski H, Brun CM, Schwarz T, Azzalin CM (2014) RNaseH1 regulates TERRA-telomeric DNA hybrids and telomere maintenance in ALT tumor cells. Nat Commun; 5:5220.
      • Bah A, Wischnewski H, Shchepachev V, Azzalin CM (2011) The telomeric transcriptome of Schizosaccharomyces pombe. Nucleic Acids Res; 40:2995-3005.
      • Chawla R, Redon S, Raftopoulou C, Wischnewski H, Gagos S, Azzalin CM (2011) Human UPF1 interacts with TPP1 and telomerase and sustains telomere leading-strand replication. EMBO J; 30:4047-4058.
      • Nergadze SG, Farnung BO, Wischnewski H, Khoriauli L, Vitelli V, Chawla R, Giulotto E, Azzalin CM (2009) CpG-island promoters drive transcription of human telomeres. RNA; 15:2186-2194.
      • Azzalin CM, Reichenback P, Khoriauli L, Giulotto E, Lingner J (2007) Telomeric repeat-containing RNA and RNA surveillance factors at mammalian chromosome ends. Science; 318:798-801. • Azzalin CM, Lingner J (2006) The human RNA surveillance factor UPF1 is required for S-phase progression and genome stability. Curr Biol; 16:433-439.

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