PNS & CNS Regeneration

Peripheral and Central Nervous System Regeneration (PNS & CNS Regeneration)

The repair of traumatic injuries to the central nervous system (CNS) presents a significant therapeutic challenge. Currently there are no effective therapies to treat brain and spinal cord injuries. The regenerative capacity of injured adult mammalian CNS is extremely limited, which leads to neurological deficits. However, the injured axons in the adult peripheral nervous system (PNS) maintain the capacity to regenerate, which leads to substantial functional recovery after injury.

We performed the first systems approach to study neural repair mechanism by pioneering work in functional genomics via the application of genome wide transcriptomics in neurons and the development of systems biology methods for analysis and data integration.

From our previous work we have shown that, by applying systems analyses we have identified core regeneration associated gene and protein networks which are differentially expressed after PNS injury (where regeneration occurs) but not after CNS injury (where regeneration fails). These gene networks responsible for PNS regeneration after injury are reproducible across various datasets. From these reproducible networks we have characterized: 

  • Core gene expression changes after PNS injury
  • Regulators responsible for regeneration after PNS injury
  • Convergent pathways responsible for PNS recovery after injury
  • Small molecule recapitulating the PNS intrinsic growth program

In future, we plan to extend these initial findings to a new level by analyzing, validating and integrating additional transcriptome profiling data generated from sorted neurons and other cell types after nerve injury to examine pathways, identify novel regulators and small molecules associated with neural repair, and ultimately generate mouse models which can regenerate their CNS neurons after injury.