Michael E. Ward, M.D., Ph.D.

My group studies inherited age-related neurodegenerative diseases, with a focus on discovering overlapping mechanisms of autosomal-dominant frontotemporal dementia (FTD). Many of the genes responsible for inherited FTD are now known, but we understand relatively little about how mutations in these genes cause disease or the functional relationship of these genes to each other. We recently discovered that patients with FTD caused by GRN mutations develop a striking lysosomal storage disease phenotype. Interestingly, a number of other FTD-related genes encode proteins involved in endocytic trafficking, suggesting the existence of converging disease mechanisms. To identify such mechanisms, we employ a combination of unbiased proteomic techniques, cellular and biochemical studies in human iPSC-derived neurons, disease models in mice, and translational studies in human subjects. Our expectation is that these studies will ultimately reveal central disease mechanisms of FTD and serve as a foundation for the development of effective disease-modifying therapies.