Lab head: Prof David J Handelsman
Location: ANZAC Research Institute (Concord Hospital)
The role of androgens in burn wound repair
Primary supervisor: Yiwei Wang
Wound healing is an innate response which involves several overlapping phases including inflammation, cell recruitment, epithelialization, matrix synthesis and tissue remodelling1. Wound repair is vitally important as it restores the dermal barrier to prevent infection and fluid loss following injury. In the anabolic, tissue forming stage of healing, such as seen in chronic wounds or uncomplicated excisions, estrogens accelerate the healing process in humans and in animal models. In contrast, androgens, acting via androgen receptor (AR), inhibitswound repair in men and male mice. However, in the catabolic, tissue losing state, typically seen in burn injury patients with over 20% total body surface area (TBSA) affected, androgens appear to support wound healing via improvement in the acute catabolic state and an acceleration of muscle protein synthesis. Preliminary research has established a burn injury model and found that AR inactivation in male mice (AR knockout, ARKO mice) significantly impaired wound healing post thermal injury, a finding opposite to that seen in cutaneous (non-burn) wound healing. These results point to a previously unrecognised, contradictory, and context-dependent role of androgens in wound healing. As these hitherto unrecognised anabolic functions of androgens open novel therapeutic avenues in treating sever burn injury, it is necessary to identify and define the precise mechanisms that shape the role of AR-mediated androgens in regulating burn wound repair. The main hypothesis is that AR-mediated androgen actions, in the catabolic state typified by burn injury, play positive roles in modifying burn injury wound healing.
Objective: Identify the role of androgen signalling in catabolic-associated burn injury wound healing
Aim 1:To determine whether AR-mediated androgen actions have systemic impacts on wound healing in catabolism associated with burn injury
Aim 2:To identify the role of the AR inwound healing and the specific healing phases: inflammation, cell recruitment, angiogenesis and matrix remodelling.
1. Skin cells isolation and harvesting from animals and in vitro organ culture
2. Introduction to small animal handling and tissue collection (mouse anatomy, tissue processing).
3. Basic histological techniques: Cutting and handling paraffin sections (microtome use) basic histological staining methods.
4. Immunohistochemistry for detection of proliferative cells within tissue.
5. Molecular biology methods: mRNA extraction, cDNA conversion to generate templates for analysis of mRNA expression levels by real-time or RT-PCR based methods. Western blot or ELISA to determine the inflammatory mediator level in the wound tissue.
Co-supervisors: Ulla Simanainen
Keywords: Andrology, wound healing