This group is investigating the reparative systems in orofacial soft tissues (oral mucosa and skeletal muscle) and how these affect clinical care. The group's studies of epithelial biology have focused primarily upon the re-growth and overgrowth of the periodontal ligament and gingival epithelium - the oral tissue at greatest risk of destruction, and possibily the most relevant to significant systemic disease (e.g. arteriosclerosis and diabetes mellitus). The group have identified phenotypic characteristics which delineate regenerative periodontal ligament cells, which include those in the stem cell compartment, that generate new periodontal ligament, cementum and alveolar bone, and thus likely to respond to regenerative stimuli. Furthermore keratinocyte growth factor (KGF) and its receptor (KGFR) have been found to be key components of gingival epithelium regeneration and hence therapeutic targets of gingival/periodontal regrowth (and causative targets of drug-induced gingival hyperplasia) and that their up-regulation is a major feature of drug-induced gingival hyperplasia, suggesting a crucial role in epithelial regeneration and a potential new target for therapeutic attack. Allied to these observations the group have found that mediators in the gingival crevicular fluid may be of value in the diagnosis and or prognostication of periodontal destruction. In relation to non-keratinised epithelium the group has shown that the cell-matrix receptor, integrin protein ß-6, is expressed only in keratinocytes during wound healing and carcinogenesis, this expression being required for specific cellular behaviours such as migration and invasion. In addition, for the first time in oral cells, the group has demonstrated that activated stromal fibroblasts (myofibroblasts) direct keratinocytes towards a more invasive phenotype. Interactions of mesenchymal oral tissue with the oral epithelium have been further investigated, the group demonstrating that oral and cutaneous epithelial cells respond to environmental signals in a similar manner but oral cells are possessed of a more activated phenotype - enabling their more rapid activation and hence accelerating the rate of oral epithelial, compared to skin, healing. This work is presently being extended by investigation of the effects of mechanical forces (with colleagues in UCL Institute of Orthopaedics; supported by grants from the UCLH and RNOH Trustees), characteristaion of epithelial-mesenchymal interactions (keratinocytes/fibroblasts) (supported by MRC studentships), identification of novel cell detection systems (with University of Surrey; supported by EPSRC studentships) and differences in healing capacity of different body compartments (Industry [Isolagen] supported).