Axis 1: Guidance of regenerative fibers

Manipulating extrinsic factors around the lesion site failed to reach the expected regeneration. However modulating intrinsic pathways of CNS neurons has shown promising results. Particularly, our work demonstrated that the simultaneous activation of mTOR, JAK/STAT and c-myc pathways allows exceptional regeneration with axons close to their targets. However it also exacerbates previously described phenomenon of misguidance with potential aberrant circuit formation. In this context, we address the yet unexplored problem of the guidance of regenerating axons in adults in order to promote the formation of a functional new circuit after injury.

To answer these critical questions, we use the combination of state of the art biochemistry, immunochemistry and imaging technics to promote correct pathfinding in-vivo.

Axis 2: Reformation of a functional circuit after injury

Our working model of long distance axon regeneration shows fibers close to their targets in the brain. This unique feature allows us to analyze the critical question of the reformation of a functional circuit after a lesion in the CNS. Indeed several questions have to be answered: can regenerative axons form proper synapses with their targets? Are the nerve functional and functional recovery can be observed? We will address those critical questions by combining state of the art imaging technics with a particular focus on whole tissue clarification.

Axis 3: Mechanisms to promote regeneration

The absence of treatment to overcome CNS regenerative failure is pointing out our lack of knowledge in the detailed mechanisms of neuronal growth, repair and their fine-tuning during development and injury. We are interested in the identification of new targets and pathways involved either in neuronal survival and/or axonal regeneration with a special focus on the translation machinery who holds the key to unlock the regenerative failure of central nervous system.

We use a combination of in-vivo models of neuronal development, CNS injury (optic nerve and spinal cord), high throughput analysis and biochemistry, to decipher translation regulation during neuronal development and injury to identify new neuroprotective and pro regenerative targets. We are particularly interested in the in-vivo TRAP approach (Translating Ribosome Affinity Purification) for targeted identification.

Axis 4: Therapeutic development to promote neuroprotection and regeneration

CNS axons are not able to regenerate. Today, there is still no treatment available in order to counteract this issue. One of our focuses is to transfer our knowledge in order to develop innovative therapeutic approaches to treat both neurodegeneration and promote regeneration in the CNS. We are currently collaborating with Dr Sabine Chierici from the Chemistry department to discover news molecules that can be tested as potential treatment.