Institut de Duve Avenue Hippocrate 75 - B1.75.04 1200 Bruxelles
The Decottignies Lab studies telomere regulation in the context of cancer and aging
How are telomeres regulated in cancer and aging and what is the impact of telomere dysfunction in cells and tissues?
Telomeres are protective structures at the ends of linear chromosomes that avoid their recognition as broken DNA. With successive cell divisions and in response to various insults, the protective function of telomeres is lost and chromosome ends are eventually sensed as broken DNA. This leads to an irreversible cell cycle arrest dubbed "senescence". Senescent cells accumulate in the aging body. This impairs cellular regeneration and drives the senescence-associated secretory phenotype, associated with chronic inflammation in aging tissues.
Using biological material from young to old healthy donors and from patients with premature aging disorders due to mutations in telomere-related genes, Anabelle Decottignies and her team study the mechanisms that drive cellular senescence. They further investigate whether the mitochondrial metabolism impacts telomere status and are studying the impact of the maternally-inherited mitochondrial DNA sequence on telomere length and protection. If premature aging can be driven by germline mutations, it can also result from inappropriate environmental or lifestyle conditions. In that context, the Decottignies lab investigates whether chemo- or radio-therapies accelerate cellular senescence in childhood cancer survivors.
Cancer develop mechanisms to avoid telomere erosion-driven cellular senescence. In most cases, they acquire replicative immortality by reactivating the expression of the telomerase enzyme. However, in a fraction of adult and pediatric solid tumors, an alternative mechanism of telomere maintenance, dubbed ALT, is activated. ALT offers interesting therapeutic opportunities as the mechanism is completely absent in normal cells. This has led the lab to develop a research axis aiming at studying the genetic requirements for ALT-positive cancer cells and understanding how the ALT mechanism modifies the metabolism of cancer cells and modulates their micro environment.
Anabelle Decottignies obtained her Master's degree in Bioengineering from the Université catholique de Louvain (UCLouvain, Belgium) in 1992. She then joined the lab of Prof. André Goffeau at UCLouvain for a PhD thesis dedicated to the biochemistry of ABC mutridrug transporters in the yeast Saccharomyces cerevisiae. She obtained her PhD in 1998 and, in 1999, she joined the lab of Sir Paul Nurse (Nobel Prize laureate in 2001) at the former Imperial Cancer Research Fund of London. There, using Schizosaccharomyces pombe fission yeast as another model organism, she studied cell cycle regulation and the mitotic spindle checkpoint. This is where she developed her strong interest for genetics. Back from London, after a short stay in her former PhD lab, she joined the de Duve Institute as group leader where she became an F.R.S-FNRS Research Associate and UCLouvain Associate Professor in 2004. In the early 2000's, she progressively moved from yeast to human cells and developed herself as a telomere expert. In 2021, Anabelle got an FNRS Research Director position.
Episkopou H, Diman A, Claude E, Viceconte N, Decottignies A.
Mol Cell (2019), 75(3):469-482.
Diman A, Boros J, Poulain F, Rodriguez J, Purnelle M, Episkopou H, Bertrand L, Francaux M, Deldicque L, Decottignies A.
Sci Adv (2016), 2 :e1600031.
Arnoult N, Van Beneden A, Decottignies A.
Nat Struct Mol Biol 2012, 19(9):948-956.