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Accueil > Unités > UMR-S 1007 "Homéostasie Cellulaire et Cancer" > Groupe "Télomères et Télomérase : Régulation physiologique et pharmacologique"

Télomères et Télomérase : Régulation physiologique et pharmacologique

par ZheruiWU - publié le , mis à jour le

  • Members of the team

E. Ségal-Bendirdjian DR CNRS, team leader
E. Nguyen, IE INSERM
J. El Hajj, PhD student
Post-doctoral position available

  • Our project

Identify antitumor strategies based on selective activation/inhibition of pathways targeting differentiation (retinoids, cAMP) or self-renewal (telomere, telomerase ). The aim is in fine to induce in tumor cells physiological signaling pathways to restore, in tumor cells, the biological responses of normal cells (differentiation, senescence, cell death) and circumvent genetic alterations the cell could have acquired (Fig. 1).

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Fig. 1 The state of the art of the project

Activation of telomerase in cancer cells constitutes an essential parameter in cell immortalization and tumor progression. Telomerase elongates telomeres and therefore compensates for the incomplete replication of chromosome ends allowing cells to divide without loosing telomere segments.Therefore, telomerase/telomere has become promising anticancer drug targets.

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Fig 2 : Visualisation of telomeres. Telomeres appear as yellow dots at the ends of chromosomes shown in blue

However, in spite of ever growing knowledge on telomere and telomerase biology, a number of questions remain to be answered : How is the repression of hTERT gene initiated and maintained in somatic cells ? What are the key regulators of telomerase ? How are regulated the non-telomeric functions of telomerase ? How is it possible to specifically target telomerase in cancer cells ?

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Fig 3 : hTERT detected in leukemic cells using an anti-hTERT antibody (stained in red). Nuclei are stained in blue (J Cell Sci 2006, 119 : 2797-2806)

The project is structured from a basic research approach focused on telomere/telomerase genetic and epigenetic regulation, to a pharmacological approach focused on the identification of signaling pathways enabling the manipulation of the plasticity of tumor cells through the targeting of telomere/telomerase for therapeutic purposes.

  • Ongoing studies

- Regulation of hTERT by retinoid and PKA
- Identification of new regulators of hTERT
- Telomere-dependent and independent functions of telomerase

  • Keywords : Telomeres, telomerase, differentiation, apoptosis, retinoids, PKA, epigenetics, transcription factors, leukemia, neuroblastoma.

  • Thesis subjects
  • Collaborations
  • Sponsors

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