Genotoxicology, signalisation and experimental radiotherapy - Institut Curie / Inserm Unit 612

Unit Director: Janet Hall

Keywords: radiation biology, radiotherapy, proton therapy, chemotherapy, DNA repair, epidemiology, ATM, PARP-1, XRCC1

The Genotoxicology, Signalling and Experimental Radiotherapy unit, with shared supervision of Inserm, is located within the Institut Curie's laboratories at Orsay. Its research priorities are twofold: to develop new radiotherapy protocols to treat cancer and to understand how genes involved in the detection and repair of DNA damage contribute to cancer predisposition and to the response of cancer patients to radiotherapy.

We are working on five main topics:

• Elucidating the early cellular responses to high dose rate (>10 Gy/s) pulsed irradiation, with the objective of implementing a clinical trial using such procedures.
• Identifying the mechanisms that underlie the differences in the biological efficiency of high-energy protons used in proton therapy relative to conventional radiation (-rays).
• Investigating how combinations of new chemotherapeutic drugs and radiotherapy interfere with radiation signalling and repair pathways.
• Deciphering how poly(ADP-ribose) polymerase-1, a DNA repair enzyme, integrates the cell's response to DNA damage with regulation of cell cycle checkpoints after exposure to ionising radiation.
• Studying the role of ATM and p53 in radiation responses. This project includes mechanistic studies on the impact of mutations and single nucleotide polymorphisms on the cellular response to radiation as well as molecular epidemiological studies on therapeutic radiation sensitivity in collaboration with the Radiotherapy Department at the Institut Curie's Hospital.

This research will contribute to improving radiotherapy and combined chemo-radiotherapy protocols, and anticipating adverse response to radiotherapy in patients.

Group(s):

• Genotoxicology, signalization and experimental radiotherapy
  Group leader: Janet Hall