Professor Mark Ferguson

Cellular and molecular mechanisms underlying wound healing, scarring, palate development and cleft palate

We are interested in fundamental cellular and molecular mechanisms regulating the normal development of the palate and what goes wrong in the birth defect of cleft palate. We also investigate fundamental mechanisms of wound healing to discover and develop new therapies to improve scarring following wounding or to accelerate the closure of chronic wounds.

Approaches taken in palate development include histology and microscopy in vitro organ and cell culture of palatal shelf explants; multiphoton confocal analysis to track cell movement or the distribution of adhesion molecules during palatal closure; immunocytochemistry and in situ hybridisation studies to localise gene products and expression; western blot, northern blot and PCR to quantitate protein/gene products and transgenic manipulations in mice to investigate under, over or misexpression of gene products. Recently the group has identified Transforming Growth Factor-beta3 as a key molecule in palate development. Transgenic mice null for TGF-beta3 develop cleft palate. Differences between TGF-beta null and normal mice are being investigated using a variety of molecular (eg, a differential display) cellular (eg, investigating the expression of putative target gene products) and genetic (eg, QTL analysis) approaches.

In wound healing, we demonstrated that embryonic wounds heal without scarring. We have ongoing fundamental investigations of the cellular and molecular differences between scar-free embryonic wound healing and scar forming adult wound healing. Already these have identified major differences eg, the extent of inflammation or the distribution and type of extra cellular matrix molecules which are potential therapeutic targets to prevent scarring during adult wound healing. A number of experiments are ongoing to investigate various pharmacological ways of manipulating adult wound healing to prevent scarring. These include exogenous administration of potential drugs and experiments in transgenic animals to verify appropriate targets. As a result of these studies three candidate anti-scarring molecules have already been developed which are entering human clinical trial. The group has also major interests in the origin of dermal stem cells during wound repair and in the quantification and measurement of scarring. We also investigate human subjects particularly those with chronic wounds such as diabetic ulcers or venous ulcers. Investigations here focus on obtaining biopsy samples from such patients to document the cellular and molecular pathogenesis of the chronic wound which then suggest novel ways in which ulcer healing could be accelerated. Trials of such wound accelerating agents are scientifically monitored both in vivo and using biopsy samples. These investigations involve a close liaison with relevant clinical departments such as Surgery, Diabetic Medicine, etc.

The group has a major involvement in the UK Centre for Tissue Engineering, Professor Ferguson was one of the three lead applicants for the IRCol (£9.7M over 6 years) and leads Clinical Programme 1 on skin/wound healing. Research involves the construction of novel tissue engineered skin equivalents incorporating smart matrices, growth factors and stem cells.

The group is extremely well equipped to international standards and there are currently some 40 postdocs, research assistants and PhD students within the programmes of palate development and wound healing. Professor Ferguson is also the co-founder of a Biotechnology spinout company - Renovo - which is developing some of the groups earlier inventions in wound healing/scar prevention. Renovo is located in the adjacent Incubator Building and interacts closely with the University Research Group. Further details can be found on www.renovo-ltd.com.