Erika L.F. Holzbaur, Ph.D.
415 Curie Boulevard
Philadelphia, PA 19104-6085
Fax: 215 573-5851
College of William and Mary, 1982.
Pennsylvania State University, 1987.
Description of Research ExpertiseResearch Interests
Key words: Dynein, cytoplasmic dynein, dynactin, microtubule motors, microtubules, microtubule dynamics, EB1.
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.
1. Investigating mechanisms of cargo coupling of cytoplasmic dynein.
2. Investigating the coordinated regulation of bidirectional microtubule-based transport.
3. Investigating the role of the microtubule plus end-binding protein EB1 in mediating cytoskeletal dynamics.
4. Investigating the cellular effects of dynactin mutations linked to motor neuron disease.
5. Investigating the role of axonal transport in motor neuron disease.
Karen Wallace-Jahn, VMD - Postdoctoral Fellow
Sandra Maday, PhD - NIH Postdoctoral Fellow
Alison Twelvetrees, PhD - Wellcome Trust Fellow
Pallavi Gopal, MD, PhD - Pathology Fellow
Amy Ghiretti, PhD - Postdoctoral Scientist
Mariko Tokito, MS - Research Specialist
Betsy Buechler McIntosh - AHA Predoctoral Fellow, Co-mentored with Mike Ostap
Eva Klinman - MD/PhD Candidate, Neuroscience
Jeff Nirschl - MD/PhD Candidate, Neuroscience
Mara Olenick - Graduate Student, Biochemistry & Biophysics
Swathi Ayloo - Graduate Student, Biology
Yvette Wong - Graduate Student, Neuroscience
Andy Moore - Graduate Student, Neuroscience
Selected PublicationsPerlson E, Jeong GB, Ross JL, Dixit R, Wallace KE, Kalb RG, Holzbaur EL.: A switch in retrograde signaling from survival to stress in rapid-onset neurodegeneration. J Neuroscience 29(31): 9903-17, Aug 2009.
Caviston J. P., Holzbaur E. L. F.: Huntingtin as an essential integrator of intracellular vesicular trafficking. Trends in cell biology 19(4): 147-55, Apr 2009.
Dixit R, Barnett B, Lazarus JE, Tokito M, Goldman YE, Holzbaur EL.: Microtubule plus-end tracking by CLIP-170 requires EB1. Proceedings of the National Academy of Sciences of the United States of America 106(2): 492-7, Jan 2009.
Dixit Ram, Levy Jennifer R, Tokito Mariko, Ligon Lee A, Holzbaur Erika L F: Regulation of dynactin through the differential expression of p150Glued isoforms. The Journal of biological chemistry 283(48): 33611-9, Nov 2008.
Levy Jennifer R, Holzbaur Erika L F: Dynein drives nuclear rotation during forward progression of motile fibroblasts. Journal of cell science 121(Pt 19): 3187-95, Oct 2008.
Caviston Juliane P, Ross Jennifer L, Antony Sheila M, Tokito Mariko, Holzbaur Erika L F: Huntingtin facilitates dynein/dynactin-mediated vesicle transport. Proceedings of the National Academy of Sciences of the United States of America 104(24): 10045-50, Jun 2007.
Perlson E, Maday S, Fu MM, Moughamian AJ, Holzbaur EL.: Retrograde axonal transport: pathways to cell death? Trends in Neurosciences 33(7): 335-44, Jul 2010.
Hendricks AG, Perlson E, Ross JL, Schroeder HW 3rd, Tokito M, Holzbaur EL: Motor coordination via a tug-of-war mechanism drives bidirectional vesicle transport. Curr Biol 20(8): 697-702, Apr 2010.
Holzbaur E. L. F., Goldman Y. E.: Coordination of molecular motors: from in vitro assays to intracellular dynamics. Curr Opin Cell Biol 22(1): 4-13, Feb 2010.