Ritchie Williamson

Research in my laboratory focuses on identifying molecular mechanisms that underlie age-related cognitive decline and dementia. Increasing data from observational studies has identified a number of potentially modifiable risk factors associated with an increased risk of developing dementia including diabetes, obesity, physical inactivity, low educational attainment, depression, smoking, and hypertension. In addition, these risk factors are additive suggesting that common signaling pathways underlie these risk factors. A key observation of a number of these risk factors is that they display alterations in energy intake/expenditure and glucose metabolism. It has previously been established that there is a link between altered energy intake, insulin sensitivity and poor cognitive performance. However, the precise molecular mechanisms that underlies the observed decrease in cognitive performance remains to be established. One possible mechanism is protein O-GlcNAcylation (a glucose-dependent post translational modification). Protein O-GlcNAcylation is altered in Alzheimer’s disease. Other than a well-established role in gene expression, how protein O-GlcNAcylation effects protein function is still to be fully determined. Work in my laboratory aims to elucidate the links between glucose-dependent alterations in protein modifications, nutritional status, and ageing to molecular mechanisms underlying dementia.