1. SELECTED RESEARCH PROJECTS
Wound repair following either burn injuries or trauma and
the associated scarring and contracture that results can lead
to a loss of movement, restricted growth, deformity and disfigurement.
Treatment of such injuries often requires multiple skin grafts
and long periods of rehabilitation and yet still leaves victims
with life-long disfigurement. Despite this, scarring is an
area of largely unmet medical need. Understanding the mechanisms
involved in wound healing and scar formation will ultimately
lead to the development of new therapies to improve the rate
and quality of wound repair and reduce scarring.
Our NHMRC funded studies, recently selected for the NHMRC's
2008 publication "10 of the Best (project grants )"
have shown that the actin-remodelling protein FlightIess I
(FliI) is an important negative regulator of wound repair
in mice. FliI deficiency enhances wound repair, with wounds
healing significantly better and exhibiting enhanced reepithelialisation.
In contrast, wounds with increased FliI expression have significantly
impaired healing. We are now extending these studies of FliI
function in wound healing to determine its effect in burn
injuries, scarring and fibrosis. In addition to our studies
to further understand the mechanism of FliI actions we are
currently developing new antibody approaches to modulate FliI
directly in wounds. These studies will potentially identify
new treatments and therapies for improving wound repair and
reducing scar formation.
Electron microscopy of FliI deficient mouse skin showing
several hemidesmosomes (HD) with electron dense attachment
plaques and associated intermediate anchoring filaments.