There are three major aspects to my research:
My research group are studying the potential mechanisms by which the accumulation of protein aggregates can lead to cellular degeneration and loss. We have discovered that the aggregating proteins implicated in Alzheimer's disease, Parkinson's disease, prion disease and late-onset diabetes all have the common ability to generate hydrogen peroxide and, subsequently, hydroxyl free radicals. The proteins involved all appear to do this through key interactions with redox-active transition metal ions, particularly those of iron and copper. Our current hypothesis is that tissue damage caused by the formation of these types of 'reactive oxygen species' could be a common mechanism of cell death in several different protein misfolding disorders.
I have recently organised a Biochemical Society Focus Meeting on metals and brain disease.
Our current research in this area is supported by The Alzheimer's Society.
A further aspect of my research is the detection of early protein aggregates, sometimes called soluble oligomers, in body fluids (cerebrospinal fluid and blood) as potential biomarkers for disease. There are two main aspects to this work:
Our current research in this area is focussed mainly on two molecular markers called α-synuclein (associated with Parkinson's disease and related disorders) and TDP 43 (associated with motor neuron disease and frontotemporal dementia). We were the first research group to detect the presence of each of these proteins in human blood plasma. Currently we are studying longitudinal changes in α-synuclein in Parkinson's disease (supported by MRC) and we are also part of large European Community (Framework 6) Project called NEUROSCREEN on the development of a multiplex system for simultaneous assay of multiple biomarkers related to neurodegenerative disease. We are also studying biomarkers in motor neuron disease (supported by The George Barton Trust).
Blocking the formation of early toxic protein aggregates, or interfering with their ability to generate reactive oxygen species, could be a novel approach to the treatment of some protein misfolding diseases. We have recently published two research papers on peptide-based aggregation inhibitors that could ultimately provide a new treatment for Alzheimer's disease and Parkinson's disease. Also, we have a very active collaboration with a biotechnology company called 'Zapaloid' on the clinical development of a similar type of new approach for the treatment of Parkinson's disease, and are part of a European Community (Framework 7) Project based on the use of nanoparticles for the improved diagnosis and treatment of Alzheimer's disease. We also have long-term funding (joint with The Department of Psychology) from the Fisher Foundation to develop improved methods for the diagnosis and treatment of Alzheimer's disease.
My research is currently supported by The Medical Research Council, The European Commission, The Alzheimer's Society, The George Barton Trust, The Fisher Foundation, and Zapaloid, with total funding well in excess of £1,000,000.
Joint Winner of Commercialisation Prize (Lancaster University Staff Award), 2006