Research Interests

Current research is on Molecular Cell Biology and Signalling, in particular in the cellular consequences of perturbation of redox homeostasis both by chemical and biological mechanisms.

• OGG1: The DNA repair protein OGG1 is critical in the repair of the oxidatively damaged base 8 oxo dG which if not removed before DNA replication mispairs with adenine and thymine causing point mutations. We are interested in the common ser326cys polymorphism in human OGG1 and are studying its activity and location compared to the “normal” protein. Work in our lab using genetically engineered cell lines has shown that the variant form of the protein is repair deficient particularly under conditions of cellular oxidative stress when it is needed most and we are currently studying the mechanistic basis for this observation.
• Cellular oxidative stress: We are using a number of experimental approaches to study the consequences of intracellular oxidative stress: These include treatment with pro-oxidants, tungsten alloys, engineered nanoparticles, depletion of the protective factor glutathione and over-expression of cytochrome P450s for which there is evidence that once “un-coupled” for example by futile substrates like polychlorinated chemicals these enzyme systems can generate substantial level of toxic free radicals in cells. We are particularly interested in oxidative DNA damage through so called “secondary genotoxicity” and the existence of potential thresholds of effect in relation to these mechanisms of toxicity.
• Cytoglobin: We are interested in cytoglobin a poorly understood homologue of haemoglobin with no known function but which may be involved in detoxification of reactive oxygen species as well as having signalling and oxygen transporter functions in a wide range of non muscle tissues especially those of a fibroblast lineage. Through collaboration with AstraZeneca were are studying the role of cytoglobin in fibrotic disease and as a potential target for drug toxicity. The cytoglobin gene also maps to a genetic disease called tylosis with oesophageal cancer (TOC) and in collaboration with The University of Liverpool we are working on the genetic regulation of this gene and trying to determine its molecular function.
• Iron cylinders: In collaboration with Professors Mike Hannon and Kevin Chipman we are investigating the cellular properties of iron and related cylinders which have potent cytostatic effects in a broad range of cell lines.

Scientific Inspiration

R Feynman.