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Erika
L. F. Holzbaur
Professor, Dept of Physiology
Cell
Biology and Physiology Program
Address
D400 Richards Building/6085
3700 Hamilton Walk
Philadelphia, PA 19104
Office tel.: 215 573-3257
Lab tel.: 215 573-3481
Fax: 215 573-5851
E-mail: holzbaur@mail.med.upenn.edu
Education
College of William and Mary: BS (Chemistry and History), 1982.
Pennsylvania State University: PhD (Biochemistry), 1987.
Worcester Foundation for Experimental Biology: Postdoctoral
Fellowship (Cell Biology), 1991.
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Research
Interests
- Microtubule-based motility.
Key words: Dynein,
cytoplasmic dynein, dynactin, microtubule motors, microtubules,
microtubule dynamics, EB1.
Search PubMed for articles
Description
of Research
Our laboratory is focused on the microtubule-based
motor cytoplasmic dynein and its activator dynactin. Dynein
and dynactin are required for vesicular trafficking, microtubule
organization, mitotic spindle assembly, and development of
polarity. We are interested in the 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 for motors, microtubules
and organelles, biochemical and cellular assays for binding
partners, live cell microscopy, and development and characterization
of transgenic mouse models for motor neuron disease.
Recent
Publications
Ross JL, Wallace K, Shuman H, Goldman YE, Holzbaur
EL. (2006) Processive bidirectional motion of dynein-dynactin
complexes in vitro. Nat Cell Biol. 8:562-70.
Levy JR, Sumner CJ, Caviston JP, Tokito MK,
Ranganathan S, Ligon LA, Wallace KE, LaMonte BH, Harmison
GG, Puls I, Fischbeck KH, Holzbaur EL. (2006) A motor neuron
disease-associated mutation in p150Glued perturbs dynactin
function and induces protein aggregation. J Cell Biol.
172:733-45.
Ligon LA, Shelly SS, Tokito MK, Holzbaur EL.
(2006) Microtubule binding proteins CLIP-170, EB1, and p150Glued
form distinct plus-end complexes. FEBS Lett. 580:1327-32.
Ligon LA, Tokito M, Finkelstein JM, Grossman
FE, Holzbaur EL. (2004) A direct interaction between cytoplasmic
dynein and kinesin I may coordinate motor activity. J.
Biol. Chem. 279:19201-19208.
LaMonte BH, Wallace KE, Holloway BA, Shelly,
SS, Ascano J, Tokito M, Van Winkle T, Howland DS, Holzbaur
EL. (2002) Disruption of dynein/dynactin inhibits axonal transport
in motor neurons causing late-onset progressive degeneration.
Neuron 34:715-727.
Lab
Rotation
Projects for 2006-2007
- Investigating mechanisms of cargo coupling
of cytoplasmic dynein.
- Investigating the coordinated regulation
of bidirectional microtubule-based transport.
- Investigating the role of the microtubule
plus end-binding protein EB1 in mediating cytoskeletal dynamics.
- Investigating the cellular effects of dynactin
mutations linked to motor neuron disease.
- Investigating the role of axonal transport
in motor neuron disease.
Lab personnel:
- Juliane Caviston – Graduate Student
Jennifer Levy – Graduate Student
Jenny Ross, PhD – Postdoctoral Fellow
Eran Perlson, PhD – Postdoctoral Fellow
Ram Dixit, Ph.D. – Postdoctoral Fellow
Erica Chevalier-Larsen, Ph.D. – Postdoctoral Fellow
Karen Wallace, VMD - Postdoctoral Fellow
Sheila Antony, BS - Research Specialist
Mariko Tokito, MS - Research Specialist
last updated 7/2006
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