Perelman School of Medicine Affiliations
Pennsylvania Muscle Institute
Mahoney Institute of Neurological Sciences
Ph.D., Pennsylvania State University, 1987
B.S., College of William and Mary, 1982
Keith R. Porter Fellowship Award
Established Investigator of the American Heart Association
Pfizer Award for Research Excellence
NIH Postdoctoral Fellowship, NINDS
Frank Malette Award for Graduate Distinction in Biochemistry
Phi Beta Kappa
American Society for Cell Biology
American Association for the Advancement of Science
Our laboratory is focused on the microtubule-based motor
cytoplasmic dynein and its activator dynactin. Dynein and
dynactin are required for vesicular trafficking, mitotic
spindle assembly, and development of polarity. We are interested
in mechanisms of force production and motor function, mechanisms
of cargo coupling and regulation, effects of dynein and dynactin
on dynamics of the cytoskeleton, and the analysis of neurodegenerative
diseases resulting from impairments in dynein/dynactin function.
Disruptions in dynein/dynactin function cause motor neuron
degeneration and muscle atrophy, leading to motor neuron
diseases similar to ALS. Approaches in the lab include in
vitro motility assays, cellular transfection assays, live
cell microscopy, and development and characterization of
transgenic mouse models for motor neuron disease.
L. A., Karki, S., Tokito, M., and Holzbaur, E. L. F. (2001)
Dynein binds to _-catenin and may
tether microtubules at adherens junctions, Nature Cell Biology
B. H., Wallace, K. E., Holloway, B. A., Shelly, S. S.,
Ascano, J., Tokito, M., Van Winkle, T., Howland,
S., and Holzbaur, E. L. F. (2002) Disruption of dynein/dynactin
in motor neurons causes late-onset progressive degeneration.
Neuron 34: 715-727.
I., Jonnakuty, C., LaMonte, B. H., Holzbaur, E. L. F.,
Tokito, M., Mann, E., Floeter,
M. K., Bidus, K., Drayna,
D., Oh, S. J., Brown, R. H., Ludlow, C. L., and Fischbeck,
K. H. (2003) Dynactin mutation in motor neuron disease.
Nature Genetics 33: 455-6.
L. A., Shelly, S. S., Tokito, M., and Holzbaur, E. L.
F. (2003) The microtubule
plus-end proteins EB1
have differential effects on microtubule polymerization.
Mol. Biol. Cell 14: 1405-17.
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a full list of publications
(searches the National Library of Medicine's PubMed database.)