Scarring and Fibrosis

Tissue injury and repair in most organs involves a change in cellular composition and the remodelling of extracellular matrix components. The overall goal of our studies is to understand the fundamental cellular and molecular mechanisms involved in normal turnover of extracellular matrix molecules during tissue repair, the way these processes are altered leading to excessive healing (scarring/fibrosis) and to identify ways of regulating these processes therapeutically.

Current research studies aim to understand the cellular and molecular mechanisms resulting in airway wall remodelling following cycles of injury and repair following asthma exacerbations. A major area of interest being addressed is the role of fungal allergen-derived proteases in airway inflammation and effects on the bronchial epithelial layer. Experimental approaches involve in vivo models, analyses well phenotyped clinical samples and manipulation of a human airway co-culture model system (Williams et al., 2009).

Post-operative adhesions are a major surgical problem, however their pathophysiology is unclear. Using histological, ultrastructural and immunocytochemical techniques, we were the first to show that human adhesions, far from being redundant scar tissue, were well vascularised and innervated, in particular by sensory fibres suggesting that they may be involved in the generation of pelvic pain stimuli (Herrick et al., 2000; 2001; Epstein et al., 2006; Wilkosz et al., 2008).

In order to understand the underlying cellular and molecular mechanisms involved in adhesion formation, a novel injury model was developed (Sulaiman et al., 2000;) and various aspects of the repair process were maniplulated using transgenic animals (Sulaiman et al., 2002) and more recently by pharmacological intervention (Gorvy et al., 2005; Epstein et al. submitted). Studies also focus on determining a role for the provisional fibrin matrix in regulating collagen deposition during tissue repair and subsequent scarring/fibrosis. Findings from three-dimensional assay culture systems and transgenic studies, suggest that a delay in fibrin clearance due to impaired fibrinolysis, results in excessive collagen deposition (de Giorgio-Miller et al., 2005). By blocking key integrin subunits, the principle cell surface receptors involved in mediating the increase in collagen gene expression by fibroblasts are being elucidated.

Principal Investigator

• Dr Sarah Herrick, PhD

Current PhD/MD Students

• James Berry- MD
• Zia Mohammad- MD
• Briony Labram
• Akshita Patil
• Abdullah Al-Kahtani

Staff

• Louise Walkin
• Sara Namvar
• Kanwal Sakhi