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

Investigator

Inherited Neurodegenerative Diseases Unit

NINDS

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Building 35, Room 2A-209
35 Convent Drive
Bethesda, MD 20892-3704

301-594-6017

wardme@nih.gov

Research Topics

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.

Biography

Dr. Ward received his B.S. from Kenyon College in 1999 and M.D. and Ph.D. degrees from Washington University in St. Louis in 2007. As a graduate student, he worked in Yi Rao’s lab and studied the regulation of cell migration during neurodevelopment. Following a neurology residency at the University of California in San Francisco, he sub-specialized in behavioral neurology and completed a postdoctoral fellowship in Li Gan’s lab studying basic mechanisms of frontotemporal dementia. As a fellow he received an American Brain Foundation CRTF award and a NIH K08 career development award. In 2015 he joined the NINDS as an Assistant Clinical Investigator. His research focuses on identifying intersecting mechanisms of neurodegenerative diseases, with an ultimate goal of developing targeted, disease-modifying therapies for affected patients.

Selected Publications

Ramos DM, Skarnes WC, Singleton AB, Cookson MR, Ward ME. Tackling neurodegenerative diseases with genomic engineering: A new stem cell initiative from the NIH. Neuron. 2021;109(7):1080-1083.
Wu W, Hill SE, Nathan WJ, Paiano J, Callen E, Wang D, Shinoda K, van Wietmarschen N, Colón-Mercado JM, Zong D, De Pace R, Shih HY, Coon S, Parsadanian M, Pavani R, Hanzlikova H, Park S, Jung SK, McHugh PJ, Canela A, Chen C, Casellas R, Caldecott KW, Ward ME, Nussenzweig A. Neuronal enhancers are hotspots for DNA single-strand break repair. Nature. 2021;593(7859):440-444.
Fernandopulle MS, Lippincott-Schwartz J, Ward ME. RNA transport and local translation in neurodevelopmental and neurodegenerative disease. Nat Neurosci. 2021;24(5):622-632.
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;104(2):239-255.e12.
Liao YC, Fernandopulle MS, Wang G, Choi H, Hao L, Drerup CM, Patel R, Qamar S, Nixon-Abell J, Shen Y, Meadows W, Vendruscolo M, Knowles TPJ, Nelson M, Czekalska MA, Musteikyte G, Gachechiladze MA, Stephens CA, Pasolli HA, Forrest LR, St George-Hyslop P, Lippincott-Schwartz J, Ward ME. RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether. Cell. 2019;179(1):147-164.e20.