Contact

Address:
Department of Neuroscience
The Ohio State University
Rightmire Hall
1060 Carmack Road
Columbus, OH 43210
Phone: 614-292-1205
Fax: 614-292-5379

For information about how you can support Ohio State axonal transport research: Leigh Briggs, Director of Development, Neurosciences, 614-293-4584

For information about career or training opportunities in this lab, contact Anthony Brown, PhD brown.2302@osu.edu

BrownImageRTFThe Brown Lab at Ohio State is devoted to the study of the cytoskeleton of nerve cells and the mechanism of axonal transport.

The lab, which is part of the Ohio State Neurological Institute, is focused on the understanding the biology of neurofilaments – a major structural component of brain cells – in health and disease. Towards this goal, the lab uses a broad range of cellular and molecular techniques – including light and electron microscopy, live-cell fluorescence imaging, protein biochemistry and nerve cell culture – to study the transport and assembly dynamics of neurofilaments in nerve cells.

Our Team

Our leaders

Anthony Brown, PhD

Professor, Department of Neuroscience

Dr. Brown received his postdoctoral training at Case Western Reserve University and Temple University. He and his team of cell biologists study the cytoskeleton of nerve cells and the mechanisms of slow axonal transport. His studies have focused on the abnormalities of axonal transport of neurofilaments, which are thought to underlie the etiology of a number of neurodegenerative diseases, most notably amyotrophic lateral sclerosis.

Staff

Dan Fenn, BS

Graduate Student

fenn.35@osu.edu

Paula Monsma, MS

Research Assistant

monsma.1@osu.edu

Atsuko Uchida, PhD

Research Associate

uchida.11@osu.edu

Elizabeth Stone

Graduate Student

stone.655@osu.edu

Alumni

Our leaders

Staff

Nael Alami, PhD

Graduate Student, 2004-2009

Gulsen Colakoglu, PhD

Graduate Student, 2004-2009

Kitty Jensen, PhD

Research Associate, 2002-2005

Tom Koehnle, PhD

Undergraduate Student, 1997-1998

Niraj Trivedi, PhD

Post-Doctoral Fellow, 2004-2007

Cynthia Walker, BS

Research Assistant, 2010-2012

Lei Wang, PhD

Graduate Student, 1998-2001

Lina Wang, PhD

Graduate Student, 2006-2011

Yanping Yan, PhD

Graduate Student, 2000-2005

Current Projects

Current Projects

 

Current Projects

The Brown laboratory studies the cytoskeleton of nerve cells and the mechanism of axonal transport with the goal of understanding the molecular mechanism of neurofilament assembly and transport and how these processes are regulated in health and disease. This effort is broken into two primary research activities:

  1. Live-cell fluorescence imaging is used in combination with a molecular, genetic and biochemical approaches to investigate the axonal transport and assembly dynamics of neurofilaments in cultured nerve cells.
  2. Investigations into the assembly dynamics of neurofilament proteins and other intermediate filament proteins in cultured cells using cell fusion, photobleaching, and photoactivation strategies in combination with conventional and photoactivatable fluorescent fusion proteins.
Recent Publications

Recent Publications

Recent Publications

Li, Y., Brown, A. and Jung, P. 2014. Deciphering the axonal transport kinetics of neurofilaments using the fluorescence photoactivation pulse-escape method. Physical Biology, 11:026001. 


Monsma, P.C., Li, Y., Fenn, J.D., Jung, P. and Brown, A. 2014. Local regulation of neurofilament transport by myelinating cells. Journal of Neuroscience, 34:2979-88.

Uchida, A,. Çolako─člu, G., Wang, L., Monsma, P.C. and Brown, A. 2013. Severing and end-to-end annealing of neurofilaments in neurons. Proceedings of the National Academy of Sciences USA, 110:E2696–E2705.

Brown, A. 2013. Axonal transport. In “Neuroscience in the 21st century”, ed. D.W. Pfaff, Springer, New York, pp. 255-308.

Brown, A. and Jung, P. 2013. A critical reevaluation of the stationary axonal cytoskeleton hypothesis. Cytoskeleton, 70:1-11.

Monsma, P.C. and Brown, A. 2012. FluoroMyelin™ Red is a bright, photostable and non-toxic fluorescent stain for live imaging of myelin. Journal of Neuroscience Methods, 209:344-350.

Taylor, N.J., Wang, L. and Brown, A. 2012. Neurofilaments are flexible polymers that often fold and unfold but they move in a fully extended configuration. Cytoskeleton, 69:535-544.
Movies associated with this publication [Click here to get QuickTime]:

Li, Y., Jung, P. and Brown, A. 2012. Axonal transport of neurofilaments: a single population of intermittently moving polymers. Journal of Neuroscience, 32:746-758.

Yuan, L., Zheng, Y.F., Zhu, J., Wang, L. and Brown, A. 2012. Object tracking with particle filtering in fluorescence microscopy images: application to the motion of neurofilaments in axons. IEEE Transactions on Medical Imaging, 31:117-130.

Wang, L. and Brown, A. 2010. A hereditary spastic paraplegia mutation in kinesin-1A/KIF5A disrupts neurofilament transport. Molecular Neurodegeneration, 5:52.

Movies associated with this publication:

  • Neurofilament movement in a cortical neuron (5.9 MB) [view movie]
  • Neurofilament movement in a cortical neuron (17.7 MB) [view movie]
  • Neurofilament movement in a cortical neuron (17.1 MB) [view movie]
  • Neurofilament movement in a cortical neuron expressing N256S-kinesin-1A (8.6 MB) [view movie]
  • Neurofilament movement in a cortical neuron expressing wild type kinesin-1A (6.8 MB) [view movie]
  • Microtubule plus-end “comets” in a cortical neuron expressing YFP-EB1 (3.6 MB) [view movie]

Uchida, A., Alami, N.H. and Brown, A. 2009. Tight functional coupling of kinesin-1A and dynein motors in the bidirectional transport of neurofilaments. Molecular Biology of the Cell, 20:4997–5006.

Movies associated with this publication:

  • Neurofilament movement in a wild type neuron (5.9 MB) [view movie]
  • Low frequency of neurofilament movement in a kinesin-1A knockout neuron (5.4 MB) [view movie]
  • An anterogradely moving neurofilament in a kinesin-1A knockout neuron (0.29 MB) [view movie]
  • A retrogradely moving neurofilament in a kinesin-1A knockout neuron (0.99 MB) [view movie]
  • Kinesin-1A knockout neuron rescued by expressing kinesin-1A (5.1 MB) [view movie]

Jung, P. and Brown, A. 2009. Modeling the slowing of neurofilament transport along mouse sciatic nerve. Physical Biology 6:046002.

Çolako─člu, G. and Brown, A. 2009. Intermediate filaments exchange subunits along their length and elongate by end-to-end annealing. Journal of Cell Biology, 185:769-777.

Movies associated with this publication:

  • Chimeric filament formed by end-to-end annealing (0.43 MB) [view movie]
  • Chimeric filament formed by end-to-end annealing(0.36 MB) [view movie]
  • Circular filament formed by end-to-end annealing (0.43 MB) [view movie]

Alami, N.H., Jung, P. and Brown, A. 2009. Myosin Va increases the efficiency of neurofilament transport by decreasing the duration of long-term pauses. Journal of Neuroscience, 29:6625-6634.

Movies associated with this publication:

  • Movement of a neurofilament in a dilute lethal SCG neuron [view movie]

Brown, A. 2009. Slow axonal transport. In “New Encyclopedia of Neuroscience”, ed. Larry R. Squire, Academic Press, Oxford, Vol. 9, pp. 1-9.

Yan, Y., Jensen, K. and Brown, A. 2007. The polypeptide composition of moving and stationary neurofilaments. Cell Motility and the Cytoskeleton, 64:299-309.

Trivedi, N., Jung, P. and Brown, A. 2007. Neurofilaments switch between distinct mobile and stationary states during their transport along axons. Journal of Neuroscience 27:507-516.

Movies associated with this publication:

  • Pulse escape movie, 5 second intervals (11.5 MB) [view movie]
  • Pulse escape movie, 5 minute intervals (6.5 MB) [view movie]
  • Flash™ animation of fluorescence photobleaching strategy (0.15 MB) [view movie]
  • Flash™ animation of fluorescence photoactivation strategy (0.12 MB) [view movie]

Craciun, G., Brown, A., Friedman, A. 2005. A dynamical system model of neurofilament transport in axons. Journal of Theoretical Biology 237:316322.

Brown, A., Wang, L. and Jung, P. 2005. Stochastic simulation of neurofilament transport in axons: the “stop and go” hypothesis. Molecular Biology of the Cell 16:4243-4255.

Movies associated with this publication:

  • Simulation of the movement of pulse of radiolabeled neurofilaments (0.7 MB) [view movie]
  • Simulation of the movement of neurofilaments in mouse spinal motor axons (0.9 KB) [view movie]
  • Graphic representation of the simulated moving and pausing behavior (3.6 KB) [view movie]

Yan, Y. and Brown, A. 2005. Neurofilament polymer transport in axons. Journal of Neuroscience 25:7014-7021.

Movies associated with this publication:

  • Capture of a neurofilament moving through a naturally occuring gap (4.0 MB) [view movie]

Uchida, A. and Brown, A. 2004. Arrival, reversal and departure of neurofilaments at the tips of growing axons. Molecular Biology of the Cell 15:4215-4225.

Movies associated with this publication:

  • Movement of a neurofilament into a growth cone (1.6 MB) [view movie]
  • Movement of a neurofilament into a growth cone (8.7 MB) [view movie]
  • Departure of a neurofilament from a growth cone (1.5 MB) [view movie]
  • Reversal of a neurofilament in a growth cone (3.1 MB) [view movie]
  • Reversal of a neurofilament in a growth cone (1.7 MB) [view movie]
  • Flash™ animation: hypothesis for neurofilament fate at axon tips (3.6 KB) [view movie]

Brown, A. 2003. Live-cell imaging of slow axonal transport. Methods in Cell Biology 71:305-323.

Brown, A. 2003. Axonal transport of membranous and non-membranous cargoes: a unified perspective. Journal of Cell Biology 160:817-821.

Wang, L. and Brown, A. 2002. Rapid movement of microtubules in axons. Current Biology 12:1496-1501.

Movies associated with this publication:

  • Movement of a microtubule in a photobleached axon (2.8 MB) [view movie]
  • Movement of a microtubule in a photobleached axon (2.6 MB) [view movie]

Wang, L. and Brown, A. 2001. Rapid intermittent movement of axonal neurofilaments observed by fluorescence photobleaching. Molecular Biology of the Cell 12:3257-3267.

Movies associated with this publication:

Brown, A. 2000. Slow axonal transport: stop and go traffic in the axon. Nature Reviews Molecular Cell Biology 1:153-156.

Wang, L., Ho, C.-L., Sun, D., Liem, R.K.H. and Brown, A. 2000. Rapid movement of axonal neurofilaments interrupted by prolonged pauses. Nature Cell Biology 2:137-141.

Movies associated with this publication:

  • Several filaments moving anterogradely (1.6 MB) [view movie]
  • Fast filament passing pausing filament (0.6 KB) [view movie]

Koehnle, T.J. and Brown, A. 1999. Slow axonal transport of neurofilament protein in cultured neurons. Journal of Cell Biology 144:447-458.

Brown, A. 1998. Contiguous phosphorylated and non-phosphorylated domains along axonal neurofilaments. Journal of Cell Science 111:455-467.

Brown, A. 1997. Visualization of single neurofilaments by immunofluorescence microscopy of splayed axonal cytoskeletons. Cell Motility and the Cytoskeleton 38:133-145.

Baas, P.W. and Brown, A. 1997. Slow axonal transport: the polymer transport model. Trends in Cell Biology 7:380-384.

Brown, A. and Lasek, R.J. 1995. Polylysine cross-links axoplasmic neurofilaments into tight bundles. Cell Motility and the Cytoskeleton 31:9-21.

Black, M.M. and Brown, A. 1993. Sites of microtubule assembly in growing axons. In Neuronal Cytoskeleton: Morphogenesis, Transport and Synaptic Transmission (Hirokawa, N., ed.), Japan Scientific Societies Press, CRC Press, 171-182.

Brown, A. and Lasek, R.J. 1993. Neurofilaments move apart freely when released from the circumferential constraint of the axonal plasma membrane. Cell Motility and the Cytoskeleton 26:313-324.

Baas, P.W., Ahmad, F.J., Pienkowski, T.P., Brown, A. and Black, M.M. 1993. Sites of microtubule stabilization for the axon. Journal of Neuroscience 13:2177-2185.

Brown, A., Li, Y., Slaughter, T. and Black, M.M. 1993. Composite microtubules of the axon: quantitative analysis of tyrosinated and acetylated tubulin along individual microtubules. Journal of Cell Science 104:339-342.

Brown, A., Slaughter, T.S. and Black, M.M. 1992. Newly assembled microtubules are concentrated in the proximal and distal regions of growing axons. Journal of Cell Biology 119:867-882.

Baas, P.W., Slaughter, T.S., Brown, A. and Black, M.M. 1991. Microtubule dynamics in axons and dendrites. Journal of Neuroscience Research 30:134-153.

Sahenk, Z. and Brown, A. 1991. Weak-base amines inhibit the anterograde-to-retrograde conversion of axonally transported vesicles in nerve terminals. Journal of Neurocytology 20:365-375.

Brown, A. and Lasek, R.J. 1990. Studying the cytoskeleton of the squid giant axon. In Squid as experimental animals (Gilbert, D.L., Adelman, W.J., Jr. and Arnold, J.M., eds.), Plenum Publishing Corporation, N.Y., 235-302.

Brown, A. and Eagles, P.A.M. 1986. Squid neurofilaments: phosphorylation and Ca++-dependent proteolysis in situ. Biochemical Journal 239:191-197.

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