My research interests include the mechanisms involved in the pathogenesis of neurodegenerative diseases. Several ongoing projects use transgenic models to study Alzheimer''''s disease (AD), Parkinson''''s disease (PD) and Tau-based dementias.

1) The tau project examines several transgenic mouse models that overexpress human tau transgenes; we are then able to study both the normal and abnormal biology of tau. Tau tangles are one of the hallmark features of AD, and pathogenic mutations have been identified in tau associated with frontal temporal lobe dementia (FTD). We are exploring the role of phosphorylation in tau pathogenesis, the evolution of tangles, signal transduction pathways involved between Abeta and tau tangle formation, the role of cholesterol in tangle formation, and pharmacological strategies to prevent tangle formation.

2) We have been modeling PD through the over-expression of synuclein and are researching how synuclein impacts cell viability; we also study the functional consequences of Lewy body formation. In addition, my lab collaborates with another lab working to identify additional genetic causes of PD. Other genes will be very useful in teasing the pathogenic mechanisms apart.

3) The AD project aims to study therapeutic approaches to the treatment of AD, including the mechanism of action of Abeta vaccination. We are also using our models to develop diagnostic imaging protocols, especially MRI, in collaboration with other NKI scientists.