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Investigator

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

Inherited Neurodegenerative Diseases Unit


Building 35 Room 2A-209
35 Convent Drive
Bethesda MD 20892-3704
Office: 301-594-6017
Lab: 301-402-1924

wardme@nih.gov

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.



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.

Staff Image
  • Michael Fernandopulle, B.S.
    MD/PhD Student (OxCam program)

  • Mari Gachechiladze, B.S.
    Postbaccalaureate IRTA

  • Ling Hao, Ph.D.
    Postdoctoral IRTA Fellow

  • Stewart Humble, B.S.
    MD/PhD Student (OxCam program)

  • Maia Parsadanian
    Laboratory Manager

  • John Stubbs, B.S.
    Postbaccalaureate IRTA

  • 1) Wang C*, Ward ME*, Chen R, Liu K, Tracy T, Chen X, Xie M, Sohn P, Ludwig C, Meyer-Franke A, Ding S, Gan L. (2017)
  • Scalable production of iPSC-derived human neurons to identify novel tau-lowering compounds by high-content screening
  • Stem Cell Reports, In Press *co-first authors
  • 2) 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* (2017)
  • Individuals with progranulin haploinsufficiency exhibit features of neuronal ceroid lipofuscinosis
  • Science Translational Medicine , PMID: 28404863 (*co-corresponding authors)
  • 3) Krabbe G, Minami SS, Etchegaray JI, Taneja P, Djukic B, Davalos D, Le D, Lo I, Zhan L, Reichert MC, Sayed F, Merlini M, Ward ME, Perry DC, Lee SE, Sias A, Parkhurst CN, Gan WB, Akassoglou K, Miller BL, Farese RV Jr, Gan L. (2017)
  • Microglial NFκB-TNFα hyperactivation induces obsessive-compulsive behavior in mouse models of progranulin-deficient frontotemporal dementia
  • Proc Natl Acad Sci U S A , 2017 May 9;114(19):5029-5034. doi: 10.1073/pnas.17
  • 4) Casaletto, K.B.*, Ward, M.E.*, Baker, N.S., Bettcher, B.M., Gelfand, J.M., Li, Y., Chen, R., Dutt, S., Miller, B., Kramer, J.H., Green, A.J. (2016)
  • Retinal thinning is uniquely associated with medial temporal lobe atrophy in neurologically normal older adults.
  • Neurobiology of Aging , 2017. Mar;51:141-147. , doi: 10.1016/j.neurobiolaging (*co-first authors)
  • 5) S. Sakura Minami, Binggui Sun, Ketul Popat, Tiina Kauppinen, Mike Pleiss, Yungui Zhou, Michael E. Ward, Paul Floreancig, Lennart Mucke, Tejal Desai, and Li Gan (2015)
  • Selective Targeting of Microglia by Quantum Dots
  • J Neuroinflammation , 9, 22
  • 6) Cho SH, Chen J, Ward ME, Gao F, Krabbe G, Sohn P, Lo I, Minami S, Devidze N, Zhou Y, Coppola G, Gan L (2015)
  • SIRT1 deficiency in microglia contributes to cognitive decline in aging and neurodegeneration via epigenetic regulation of IL-1β.
  • J Neurosci, 2015 Jan 14; 35(2):807-18, PMID: 25589773; PMCID: PMC4293425
  • 7) Ward, M.E., A. Taubes, R. Chen, B.L. Miller, C.F. Sephton, J.M. Gelfand, S. Minami, J. Boscardin, L.H. Martens, W.W. Seeley, G. Yu, J. Herz, A.J. Filiano, A.E. Arrant, E.D. Roberson, T.W. Kraft, R.V. Farese, A. Green, and L. Gan. (2014)
  • Early retinal neurodegeneration and impaired Ran-mediated nuclear import of TDP-43 in progranulin-deficient FTLD.
  • Journal of Experimental Medicine, doi:10.1084, /jem.20140214.
  • 8) Minami S, Min S, Krabbe G, Wang C, Zhou Y, Asgarov R, Li Y, Martens L, Elia L, Ward ME, Mucke L, Farese R, Gan L (2014)
  • Progranulin Modulates Innate Immunity and Protects Against Amyloid β Deposition and Toxicity in Mouse Models of Alzheimer's Disease
  • Nature Medicine, 20, 1099-1100
  • 9) Feng Y, Ngu H, Alford SK, Ward M, Yin F, Longmore GD (2013)
  • alpha-Actinin1 and 4 tyrosine phosphorylation is critical for stress fiber establishment, maintenance and focal adhesion maturation
  • Exp Cell Res, May 1;319(8), 1124-35
  • 10) Ward ME, Miller BL (2011)
  • Potential Mechanisms of Progranulin-deficient FTLD.
  • J Mol Neurosci, Nov;45(3), 574-82
  • 11) Pratt SJ, Epple H, Ward M, Feng Y, Braga VM, Longmore GD. (2005)
  • The LIM protein Ajuba influences p130Cas localization and Rac1 activity during cell migration
  • J. Cell Biol, Feb 28;168(5), 813-24
  • 12) Kisseleva M, Feng Y, Ward M, Song C, Anderson RA, Longmore GD (2005)
  • The LIM protein Ajuba regulates phosphatidylinositol 4,5-bisphosphate levels in migrating cells through an interaction with and activation of PIPKI alpha
  • Mol Cell Biol, May;25(10), 3956-66.
  • 13) Ward ME, Jiang H, Rao Y (2005)
  • Regulated Formation and Selection of Neuronal Processes Underlie Directional Guidance of Neuronal Migration
  • Molecular and Cellular Neuroscience, vol. 30, pp378-387
  • 14) Ward ME, Wu JY, Rao Y (2004)
  • (From the cover) Visualization of spatially and temporally regulated N-WASP activity during cytoskeletal reorganization in living cells
  • Proc Natl Acad Sci USA 2004 Jan 27, 101(4), 970-4
  • 15) Ward ME and Rao Y (2004)
  • Investigations of neuronal migration in the central nervous system
  • Methods Mol Biol, 294, 137-56
  • 16) Ungewickell A, Ward ME, Ungewickell E, Majerus PW (2004)
  • The inositol polyphosphate 5-phosphatase Ocrl associates with endosomes that are partially coated with clathrin
  • Proc Natl Acad Sci USA, 2004 Sep 14;101(37), 13501-6
  • 17) Ward M, McCann C, DeWulf M, Wu JY, Rao Y (2003)
  • Distinguishing between directional guidance and motility regulation in neuronal migration
  • Journal of Neuroscience 2003 Jun, 15;23(12), 5170-7
  • 18) Rao Y, Wong K, Ward M, Jurgensen C, Wu JY (2002)
  • Neuronal migration and molecular conservation with leukocyte chemotaxis
  • Genes Dev. 2002 Dec 1, 16(23), 2973-84.
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