Michael E. Ward, M.D., Ph.D.
Inherited Neurodegenerative Diseases Unit
Building 35, Room 2A-209
35 Convent Drive
Bethesda, MD 20892-3704
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.
Tian R, Gachechiladze MA, Ludwig CH, Laurie MT, Hong JY, Nathaniel D, Prabhu AV, Fernandopulle MS, Patel R, Abshari M, Ward ME, Kampmann M. CRISPR Interference-Based Platform for Multimodal Genetic Screens in Human iPSC-Derived Neurons. Neuron. 2019.
Fernandopulle MS, Prestil R, Grunseich C, Wang C, Gan L, Ward ME. Transcription Factor-Mediated Differentiation of Human iPSCs into Neurons. Curr Protoc Cell Biol. 2018;79(1):e51.
Wang C, Ward ME, Chen R, Liu K, Tracy TE, Chen X, Xie M, Sohn PD, Ludwig C, Meyer-Franke A, Karch CM, Ding S, Gan L. Scalable Production of iPSC-Derived Human Neurons to Identify Tau-Lowering Compounds by High-Content Screening. Stem Cell Reports. 2017;9(4):1221-1233.
Ward ME, Chen R, Huang HY, Ludwig C, Telpoukhovskaia M, Taubes A, Boudin H, Minami SS, Reichert M, Albrecht P, Gelfand JM, Cruz-Herranz A, Cordano C, Alavi MV, Leslie S, Seeley WW, Miller BL, Bigio E, Mesulam MM, Bogyo MS, Mackenzie IR, Staropoli JF, Cotman SL, Huang EJ, Gan L, Green AJ. Individuals with progranulin haploinsufficiency exhibit features of neuronal ceroid lipofuscinosis. Sci Transl Med. 2017;9(385).
Ward ME, Gelfand JM, Lui LY, Ou Y, Green AJ, Stone K, Pedula KL, Cummings SR, Yaffe K. Reduced contrast sensitivity among older women is associated with increased risk of cognitive impairment. Ann Neurol. 2018;83(4):730-738.
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This page was last updated on September 19th, 2019