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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.

Ward Lab Page

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

  • Jenn Colon, Ph.D.
    Postdoctoral Fellow

  • Andrea Solano Cruz
    Post baccalaureate IRTA Fellow

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

  • Saadia Hasan, B.S.
    MD/PhD Student (University College London)

  • Sarah Hill, Ph.D.
    Postdoctoral Fellow

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

  • Chris King, Ph.D.
    Postdoctoral Fellow

  • Maia Parsadanian
    Laboratory Manager

  • 1) Ruilin Tian, Mariam A Gachechiladze, Connor H Ludwig, Matthew T Laurie, Jason Y Hong, Diane Nathaniel, Anika V Prabhu, Michael S Fernandopulle, Rajan Patel, Michael E Ward*, Martin Kampmann* (2019)
    •
  • CRISPR-based platform for multimodal genetic screens in human iPSC-derived neurons
  • Neuron, (*co-corresponding authors)
  • 2) Ya-Cheng Liao, Michael Fernandopulle, Guozhen Wang, Heejun Choi, Ling Hao, Catherine M Drerup, Seema Qamar, Jonathon Nixon-Abell, Yi Shen, William Meadows, Michele Vendruscolo, Tuomas Knowles, Matthew Nelson, Magda Czekalska, Greta Musteikyte, Rajan Patel, Christina Stephens, Amalia Pasolli, Lucy Forrest, Peter St George-Hyslop, Jennifer Lippincott-Schwartz* and Michael E Ward* (2019)
    •
  • RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether
  • Cell, (*co-corresponding authors), F1000Prime Recommended
  • 3) Zhang YJ, Guo L, Gonzales PK, Gendron TF, Wu Y, Jansen-West K, O'Raw AD, Pickles SR, Prudencio M, Carlomagno Y, Gachechiladze MA, Ludwig C, Tian R, Chew J, DeTure M, Lin WL, Tong J, Daughrity LM, Yue M, Song Y, Andersen JW, Castanedes-Casey M, Kurti A, Datta A, Antognetti G, McCampbell A, Rademakers R, Oskarsson B, Dickson DW, Kampmann M, Ward ME, Fryer JD, Link CD, Shorter J, Petrucelli L. (2019)
    •
  • Heterochromatin anomalies and double-stranded RNA accumulation underlie C9orf72 poly(PR) toxicity
  • , Science
  • 4) A. J. Willsey, M. T. Morris, S. Wang, H. R. Willsey, N. Sun, N. Teerikorpi, T. B. Baum, G. Cagney, K. J. Bender, T. A. Desai, D. Srivastava, G. W. Davis, J. Doudna, E. Chang, V. Sohal, D. H. Lowenstein, H. Li, D. Agard, M. J. Keiser, B. Shoichet, M. von Zastrow, L. Mucke, S. Finkbeiner, L. Gan, N. Sestan, M. E. Ward, R. Hüttenhain, T. J. Nowakowski, H. J. Bellen, L. M. Frank, M. K. Khokha, R. P. Lifton, M. Kampmann, T. Ideker, M. W. State, and N. J. Krogan (2018)
    •
  • The Psychiatric Cell Map Initiative: A Convergent Systems Biological Approach to Illuminating Key Molecular Pathways in Neuropsychiatric Disorders
  • Cell
  • 5) Ward ME*, Gelfand JM*, Lui L-Y, Ou Y, Green AJ, Stone K, Pedula K, Cummings S, Yaffe (2018)
    •
  • Reduced contrast sensitivity among older women is associated with increased risk of cognitive impairment
  • Annals of Neurology, (*co-first authors)
  • 6) Y. Shi, S. Lin, K. A. Staats, Y. Li, W.-H. Chang, S.-T. Hung, E. Hendricks, G. R. Linares, Y. Wang, E. Y. Son, X. Wen, K. Kisler, B. Wilkinson, L. Menendez, T. Sugawara, P. Woolwine, M. Huang, M. J. Cowan, B. Ge, N. Koutsodendris, K. P. Sandor, J. Komberg, V. R. Vangoor, K. Senthilkumar, V. Hennes, C. Seah, A. R. Nelson, T.-Y. Cheng, S.-J. J. Lee, P. R. August, J. A. Chen, N. Wisniewski, V. Hanson-Smith, T. G. Belgard, A. Zhang, M. Coba, C. Grunseich, M. E. Ward, L. H. van den Berg, R. J. Pasterkamp, D. Trotti, B. V. Zlokovic, and J. K. Ichida (2018)
    •
  • Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons
  • Nature Medicine
  • 7) Fernandopulle M, Prestil R, Grunseich, C, Wang C, Gan L, Ward ME (2018)
    •
  • Transcription-factor mediated differentiation of iPSCs into neurons
  • Current Protocols in Cell Biology
  • 8) Robert Krencik, Kyounghee Seo, Jessy V. van Asperen, Nupur Basu, Caroline Cvetkovic, Saba Barlas, Robert Chen, Connor Ludwig, Chao Wang, Michael E. Ward, Li Gan, Philip J. Horner, David H. Rowitch, Erik M. Ullian (2017)
    •
  • Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes
  • Stem Cell Reports
  • 9) 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
  • 10) 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
  • 11) 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, (*co-first author)
  • 12) 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 , (*co-first authors)
  • 13) 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
  • 14) 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
  • 15) 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
  • 16) 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
  • 17) 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
  • 18) Ward ME, Miller BL (2011)
    •
  • Potential Mechanisms of Progranulin-deficient FTLD.
  • J Mol Neurosci, Nov;45(3), 574-82
  • 19) 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
  • 20) 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.
  • 21) 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
  • 22) 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
  • 23) Ward ME and Rao Y (2004)
    •
  • Investigations of neuronal migration in the central nervous system
  • Methods Mol Biol, 294, 137-56
  • 24) 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
  • 25) 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
  • 26) 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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