WOUND HEALING

• Staff
  • Laboratory Head
  • Scientific Staff
  • 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

Professor Allison Cowin

Ph: 08 8161 7077

Email: allison.cowin@adelaide.edu.au

Scientific Staff

Research Staff

Students

GOALS

The Wound Healing Laboratory focuses on understanding the mechanisms involved in wound healing, scar formation and fragile skin syndromes. Using this knowledge we aim to develop potential new therapies for the treatment of wounds to help improve the repair process.

RESEARCH PROJECTS

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

Our NHMRC funded studies in collaboration with A/Prof Ruth Arkell at ANU suggest that Flii may provide a mechanistic link between cytoskeletal remodelling and induction of TGF s post-wounding potentially contributing to scar formation. Wounds in Flii deficient mice have less TGF- 1 whereas Flii overexpressing wounds have increased levels of TGF 1. Our studies this year have focused on using conditional gene manipulation technology to inducibly and specifically overexpress FliI in keratinocytes (FliIloxP x K5-CreER(T)) and fibroblasts (FliIloxP C1a-CreER(T)), separately or together ((FliIloxP x K5-CreER(T) X FliIloxPxC1a-CreER(T)). These studies are identifying if there is a cell specific effect of Flii during wound repair.

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 (EB), 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. This NHMRC funded project, in collaboration with Prof Dedee Murrell (UNSW) has revealed that elevated Flii contributes to impaired hemidesmosomes, and altered integrin ?6?4 expression which may affect the disease pathology and the healing of the resulting blisters. In collaboration with Prof Detlef Zillikens (Luebeck, Germany) and Prof Leena Bruckner-Tuderman we have used two murine models of EB and blister formation to determine the function of Flii in this disease process. Our results indicate that lowering the expression of Flii in EB patients could be a potential therapeutic approach to improving the healing outcomes of patients with fragile skin syndromes.

3. Development of Flii antibody therapy

Although Flii was thought to be solely an intracellular protein our research has shown that it is secreted both in vitro and in vivo. Subsequently we have generated and tested mouse monoclonal antibodies which neutralise Flii activity and improve healing repones. This year we have performed preclinical studies using porcine models of wound healing and have found that healing of porcine wounds is significantly improved following treatment with Flii monoclonal antibodies. A new NHMRC Development grant was awarded this year and will underpin the development of this current monoclonal antibody and will fund the production of second generation antibodies with improved binding affinities.

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

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 have revealed important new insights into the function of Flii during hair follicle development and may lead to novel therapies that allow hair regeneration to occur post burn injuries.