Research
Overarching goal of our research:
The longstanding goal of the limb regeneration field has been the identification of the underlying cellular programs that can trigger a successful regenerative response in mammals. Among land vertebrates, however, only salamanders are capable of regrowing limbs as adults. Current molecular and fossil evidence indicates that salamander limb regeneration and fish fin regeneration share a common evolutionary origin.
Our long-term research goals transit between the following basic and applied science questions, respectively:
- What regions of the genome underlie maintenance, gain and loss of regenerative capacity during vertebrate evolution?
- Is there an evolutionarily shared genetic toolkit of limb and fin regeneration that can be rekindled in regeneration-incompetent species?
Ultimately, we posit that an evolutionary framework and comparative experimental approaches are necessary for the identification of molecular and cellular mechanisms underlying limb and fin regeneration.
Comparative transcriptomic profiling of appendage regeneration
The regeneration of limbs and fins involves the recruitment and orchestration of several
cell types to rebuild a complex multi-tissue structure. To search for a shared cellular
and molecular toolkit of vertebrate appendage regeneration, our team has begun characterizing
common progenitor cell pools and molecular signals that come into action soon after
fin/limb loss. We have been deploying techniques such as spatial transcriptomics in
a comparative manner, using the axolotl, the lungfish and Polypterus.
Lungfish as research model for tail and spinal cord repair and regeneration
We have recently shown that lungfish and salamanders use a similar genetic program
to regenerate tails. As salamanders, lungfish can regenerate muscle, vertebrae and
spinal cord neurons providing a unique opportunity to identify evolutionarily conserved
cellular and molecular signals required for regeneration. We are interested in identifying
regulatory elements and gene expression profiles contributing to tail regeneration.
Cis-regulatory landscapes underlying appendage regeneration
In recent years, cis-regulatory elements (CREs) that are active during regeneration
have been identified in animals ranging from acoel worms to teleost fish. The recent
completion of genome assemblies for the highly regenerative axolotl, lungfish and
Polypterus, now enables testing of the hypothesis that evolutionarily shared CREs
regulate gene expression programs of regeneration in limbs and fins. We are interested
in identifying the evolutionarily conserved components of the regulatory program of
vertebrate appendage regeneration. Ultimately, a large multispecies dataset of regeneration-responsive
CREs will allow us to predict regenerative capacity in understudied taxa and better
understand how regeneration evolves.