Serious skin disorders count among the most devastating health conditions and most
difficult treatment challenges. These arise both from genetic diseases and from injuries,
such as the often-debilitating long-term suffering of the >500,000 serious burn victims
who are hospitalized every year in the US alone. Today's top treatments, including major
skin grafts, still struggle to overcome the key natural limitations of human skin's relatively
basic repair processes. While these generally restore structural integrity, they often
result in extensive scarring that not only causes disfigurement and accompanying
psychological trauma, but also significant loss of functionality, including impaired
sensitivity and increased susceptibility to infection.
The development of more effective skin therapies now stands to benefit greatly from
emerging new understanding of the remarkable healing abilities exhibited by naturally
regenerative vertebrates. To this end, our longstanding work on the “axolotl”
salamander, the champion among such species, is identifying critical molecules,
regulatory pathways and cellular processes underlying scar-free regeneration.
Here, we will these address central issues in skin regeneration using cutting edge
screening and analysis tools in axolotl. The aim of the project is to: 1) define the exact
role of Sall4 in the dermis and epidermis for promoting scar free skin regeneration. 2)
harness skin cell transcriptome data to define and functionally elucidate the role of
different skin cell populations in regulating scar free regeneration. 3) We will translate
our findings of the role of SALL4 in regulating collagen in axolotls into an in vitro model
of human skin regeneration and use this new knowledge to attempt to promote scar-
free wounding healing in human cells.
In summary, these experiments will reveal and characterize key differences between
the axolotl's regenerative and the mammal's non-regenerative responses to injury,
identifying molecules and pathways required for the former to assess their potential for
enhancing the latter. The ultimate aim of these studies is thus to improve quality of life
for people with chronic open wounds and dysfunctional scar tissue.