Research in the Lashuel laboratory focuses on applying integrated chemical, biophysical, and molecular/cellular biology approaches to elucidate the molecular and structural basis of protein misfolding and aggregation and the mechanisms by which these processes contribute to the pathogenesis of neurodegenerative diseases including Parkinson’s disease (PD), Alzheimer’s disease (AD),Huntington’s disease (HD) and Amytrophic Lateral Sclerosis (ALS).
Current research efforts cover the following topics: (1) elucidating the sequence, molecular and cellular determinants underlying protein aggregation, pathology spreading and toxicity; (2) developing novel chemical approaches and tools to investigate the role of post-translational modifications in regulating the function/dysfunction of proteins implicated in the pathogenesis of AD (Tau), PD (α-Synuclein), HD and ALS (TDP-43); 3) identification of biomarkers and imaging agents for early detection, monitoring of disease progression and response to therapies and disease staging; (4) developing novel cellular models to assess and validate therapeutic targets and to test disease modifying strategies based on modulating protein post-translational modifications, aggregation, pathology spreading and clearance.
Our interdisciplinary approach is centered on three major themes. First, we use chemical, biochemical and biophysical tools and methods to elucidate the molecular determinants and mechanisms that govern the misfolding and aggregation of key proteins implicated in the pathogenesis of Alzheimer’s and Parkinson’s disease. Second, our group is applying advances in synthetic chemistry and developing novel chemical methods and tools that allow for the monitoring and control of protein misfolding and aggregation inside and outside the cell with spatial and temporal resolution. These tools and molecular probes are essential for understanding the mechanisms of protein aggregation and its role in neurodegeneration. Third, we use cellular and animal models to test our mechanistic models, validate novel therapeutic targets, and assess disease modifying strategies.