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Research

 Mezger group  janvier 2017

Synopsis

Various studies suggest that fetal stress is a factor of predisposition to brain disabilities. However, there is an almost complete black box between these observations and the resulting development of associated cognitive and affective disorders. In particular, the cellular and molecular mechanisms underlying the short- and long-term effects of fetal stress in the etiology of these disabilities are largely unknown.

Main goalsSans titre

We aim at understanding the links between environmental stress and brain development and integrity. One of our major focus is the crosstalk between stress-responsive pathways and epigenetic regulations in the normal and diseased developing brain.

We address this question by studying Heat Shock transcription Factors (HSFs) that represent a unique entry point into a link between stress, epigenetics, and brain development/integrity.

 

Current research area

  • We already demonstrated that HSF2 is involved in normal brain cortical development. Our ongoing focus is to investigate its role in the mature brain. Using fetal alcohol exposure (FAE) as a paradigm of prenatal stress in mouse models, we showed that HSF2 is an essential mediator of developmental defects characteristic for Fetal Alcohol Syndrome, in response to FAE in the developing brain. A next step is to investigate the impact of this prenatal stress on adult brain.
  • We also study the dynamic interplay between HSF2 and epigenetic actors that govern HSF2 stability in the normal and stress brain. We are developping large scale strategies to investigate those aspects.
  • We identified HSF2 protein partners and are investigating how they impact on HSF2 function both in normal and stress situation. Using various cellular models, we are validating these protein interactors.

More globally, we investigate the crosstalk between diverse stress-responsive pathways and the redistribution of epigenetic actors in response to prenatal stress (hypoxia, neuroinflammation, alcohol exposure).

In that context, our team is part of the DHU PROTECT directed by Pierre Gressens in the Hôpital Robert Debré (INSERM 1141, Paris), with whom we develop projects with translational perpectives.

fundings