From, Duke University School of Medicine, USA

Will give a seminar entitled:

Fishing for mechanisms of spinal cord regeneration

Abstract:

Spinal cord regeneration is negligible in adult mammals, yet zebrafish can construct a bridge of glia and axons and recover locomotor ability after a paralyzing injury. We recently identified Hb-egfa as an ependymal progenitor-derived, instructive factor key for zebrafish spinal cord regeneration. Zebrafish deficient in hb-egfa had defective ependymal cell proliferation, tissue bridging, and axon regeneration after spinal cord transection, disrupting functional recovery. Whereas broad transgenic hb-egfa overexpression worsened innate regenerative responses, local hydrogel-assisted delivery of recombinant HB-EGF protein improved axon regeneration. Epigenetic profiling revealed an hb-egfa-associated cis-regulatory element sufficient to trigger gene expression in spinal cord injury sites. Engineering this enhancer into recombinant AAV vectors targeted gene expression to spinal cord injuries in neonatal, but not adult mice, delivering HB-EGF to crush injuries and improving axon densities. These results reveal cross-species functions for Hb-egf during spinal cord repair, and they suggest strategies to awaken innate regenerative capacity in mammals. My immediate goal as an independent investigator is to understand how Hb-egf exerts its effects, and to decipher additional mechanisms of spinal cord regeneration using zebrafish and neonatal mouse models. The ultimate goal is to uncover new pathways and paradigms controlling the balance between scarring and regeneration, and to tip this balance toward functional repair in adult mammals.