Identifying Extrinsic Mechanisms That Regulate Mammalian Regeneration

Regeneration of appendages is relatively common among invertebrates. In mammals, however, multi-tissue regeneration is restricted to the distal portion of the digit tip. Removing more than 60% of the end of the digit culminates in wound healing and fibrotic scar formation.

This raises the question of why this is so, since this restriction has major implications for therapeutic approaches to tissue repair.

My working hypothesis is that cells within the mammalian limb are intrinsically capable of responding regeneratively however are diverted towards scarring by the injury microenvironment rather than due to the availability of regeneration-competent progenitors.

To test this, we will use an interdisciplinary approach combining single cell genomic approaches, in vitro culture systems and in vivo assays to map regeneration-competent and -incompetent cellular injury microenvironments in the digit tip.

This work will aim to i) identify signalling networks important for promoting/inhibiting tissue regeneration, ii) decipher how cell behaviour is influenced by tissue mechanics, and iii) provide a functional platform to validate regeneration-specific pathways in human tissue.

By gaining an understanding of the regulatory mechanisms that promote mammalian digit tip regeneration, this will ultimately enable their targeted reactivation as a means to treat injuries and degenerative diseases in humans.