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Research Projects

Published on 27 June 2018
​DNA damage and repair in the developing brain
​Neural precursors are highly sensitive to ionizing radiation. Irradiation during brain development can severely alter cognitive abilities and behavior during adulthood. 
Our aims are: 1/ to characterize the DNA damage responses of neural stem and progenitor cells, 2/ to determine the short and long-term consequences of their activation for brain development, and 3/ to correlate them to the effects of radiation on cognitive functions and behavior. Our ultimate goal is to find new preventive — essentially based on the determination of risk factors— or therapeutic strategies against the radiation brain effects.
We have shown that the DNA damage response of fetal neural stem cells has remarkable and specific features. For instance, the G1/S checkpoint, which is considered to be a critical requirement to maintain genomic stability after DNA damage, is apparently repressed in fetal neural stem cells, probably due to several factors involved in the regulation of stem cell functions.
We are currently attempting to unveil the relative importance of the different pathways of double strand break repair, i.e. homologous recombination and non-homologous end joining, for brain development and preservation of cognitive functions after low-dose radiation exposure.

LRP1.jpg
EdU (Red) and BrdU (green) incorporated in cycling neural progenitors in the mouse embryonic brain

​Adult neural stem cell maintenance
Neurogenesis persists in restricted areas of the adult brain, where a low number of new neurons are continuously produced. Production of new neurons may be dramatically impaired by radiotherapy causing subsequent cognitive decline. Our working hypothesis is that neural stem cells resist to irradiation but remain blocked in a quiescent state. We therefore seek for signaling pathways regulating neural stem cell quiescence/proliferation in order to find new methods to restimulate endogenous neurogenesis, which could be particularly helpful to develop new regenerative medicine in various brain pathologies.

​Glioma stem-like cells
Glioblastoma multiforme is the most severe and aggressive primary tumor of the central nervous system. One current hypothesis is that a minor population of cancer cells shares several properties with neural stem cells. These glioma stem-like cells are supposed to have the capacity to resist and regenerate the tumor after anti-cancer treatments and represent thus a crucial therapeutic target. Our aim is to characterize their mechanisms of radiation resistance in the hope to find new therapeutic strategies against these tumors, which are currently incurable. We are particularly interested in the mechanisms of telomere maintenance and tissue invasiveness.​