WOUND HEALING

• Staff
  • Laboratory Head
  • Research Staff
  • Students
• Goals
• Research Projects
  1. Role of Flii in TGF-ß mediated scar formation
  2. Effect of Flii on cell adhesion, migration and proliferation and potential role in epidermolysis bullosa
  3. Development of Flii antibody therapy
  4. The Role of Flii during Hair Follicle Development, and Regeneration of Wounded Hair Follicles

STAFF

Laboratory Head

A/Prof Allison Cowin

Ph: 08 8161 7077

Email: allison.cowin@adelaide.edu.au

Research Staff

Students

GOALS

The Wound Healing Laboratory focuses on understanding the mechanisms involved in wound healing, scar formation and fibrosis. Using this knowledge we aim to develop potential new therapies for the treatment of wound and burn injuries.

RESEARCH PROJECTS

1. Role of Flii in TGF-ß mediated scar formation

Our NHMRC funded studies suggest that Flii may provide a mechanistic link between cytoskeletal remodelling and induction of TGFßs post-wounding potentially contributing to scar formation. Wounds in Flii deficient mice have less TGF-ß1 whereas Flii overexpressing wounds have increased levels of TGFß1. Our studies have shown that modulation of Flii gene expression directly affect TGF-ß expression in wounds potentially via the MAPK pathway and signalling via the Smad pathway. Understanding these important processes will help to identify new targets for modulating TGF-ß activity thereby leading to potential new mechanism-based anti-scarring therapies.

2. Effect of Flii on cell adhesion, migration and proliferation and potential role in epidermolysis bullosa

Our studies are continuing into the potential role of Flii in epidermolyisis bullosa, a skin blistering disorder which is particularly devastating in children. This disease has various forms caused by the mutations in genes which code for structural proteins at the dermal-epidermal junction resulting in diminished adhesion of skin layers and blistering. Flii is significantly elevated particularly in the most common Junctional EB subtype where hemidesmosome-anchoring filament complexes are weakened and genetic defects in one of the structural components including: integrin a6ß4, collagen XVII and major basement membrane protein laminin-5 occurs. Our results suggest that elevated Flii may contribute to impaired hemidesmosomes, and altered integrin a6ß4 which may affect the disease pathology and the healing of the resulting blisters. In collaboration with Prof Detlef Zillikens (Luebeck, Germany) we have developed a blister model which we will use to determine the function of Flii in this disease process. We have recently received NHMRC funding to continue these investigations and hope that these studies will lead to new treatments for improving blister wound repair.

3. Development of Flii antibody therapy

Over the last 2 years we have completed studies indicating that neutralisation of Flii may be a potential novel therapy for improving wound repair. Although Flii was thought to be solely an intracellular protein we have evidence that it is secreted both in vitro and in vivo. Subsequently we have generated and tested a panel of mouse polyclonal antibodies raised against specific parts of the Flii peptide crucial for Flii function. We have applied these antibodies to incisional wounds with significant improvements in wound healing being observed. Through development grant funding from the NHMRC and BioInnovation SA we are now developing monoclonal antibodies and will test these using in vitro and in vivo assays

4. The Role of Flii during Hair Follicle Development, and Regeneration of Wounded Hair Follicles

We have shown that Flii is involved in the wound healing process and regulates the growth and migration of cells in skin that are also important to hair follicle development. A greater understanding of events involved in hair follicle development, the adult hair cycle and the regeneration of hair follicles after localised injury, will be beneficial in developing means to regenerate hair follicles in repairing wounds and artificial skin to create 'functional' skin, not just a covering of the wound. While the creation of artificial skin has been beneficial for the treatment of full skin thickness burns, the absence of functional hair follicles results in the skin being dry due to the absence of hair follicle appendages such as sebaceous and sweat glands. Our ongoing investigations into the role of Flii during hair follicle development, cycling and regeneration will allow further insight into the events important for hair follicle development and may lead to novel therapies that allow hair regeneration to occur in artificial skin.

Hair follicles from whisker pads of rats and mice show a distinctive pattern of Flightless I (Flii) expression (red) after immunostaining. This suggests that Flii may play a role in homeostasis of hair follicles.