CNUP Training Faculty

Edward A. Burton, D.Phil. M.D.

Associate Professor, Neurology, Microbiology and Molecular Genetics

D.Phil. University of Oxford, UK (2000)
M.D. University of Birmingham, UK (2003)

Office: 7015 Biomedical Science Tower-3
Telephone:412-648-9720
Fax:412-648-8537
E-mail: eab25@pitt.edu
Website: http://www.neurology.upmc.edu/faculty/burton.html

The pathogenesis of diseases associated with movement disorders and the development of novel therapeutic approaches.

Research Summary:

Particular areas of focus in the Burton laboratory include the generation and characterization of novel transgenic zebrafish models to study pathogenic mechanisms in vivo, development of automated high throughput zebrafish assays for drug discovery, and the study of gene environment interactions in Parkinson's disease using novel transgenic zebrafish models and viral gene transfer to the mammalian brain. Current projects include:
• Identification, cloning, functional characterization of zebrafish orthologues of genes implicated in human neurodegenerative diseases, including DJ1, synucleins, LRRK2, microtubule associated proteins and others.
• Construction of transgenic zebrafish expressing microtubule associated proteins, synucleins, LRRK2, and other transgenes, in order to provoke neurodegeneration.
• Characterization of spontaneous and evoked behaviors in larval and adult zebrafish, which could be used as assay end-points that are not biased to preconceptions about molecular mechanism, in order to exploit zebrafish models of neurodegenerative diseases for the discovery of novel pathogenic pathways and therapeutic compounds.
• Exploitation of the optical transparency of zebrafish in order to allow live in vivo imaging of neurodegeneration, regeneration and repair, and changes in mitochondrial function.
• Determination of mechanisms by which environmental triggers known to provoke neurodegeneration interact with alterations in genetic background in vivo, using novel transgenic zebrafish lines.
• Design and generation of genetically engineered viral vectors that modulate gene expression in vivo in the mammalian brain, allowing characterization of the functional effects of altered gene expression in adult animals, and determination of the interactions between genes of interest, and environmental and toxic triggers known to provoke neurodegeneration.

Selected Publications:

Münzel, E., Schaefer, K., Obirei, B., Kremmer, E., Burton, E. A., Kuscha, V., Becker, C. G., Brösamle, C., Williams, A., Becker, T. Claudin k is specifically expressed in cells that form myelin during development of the nervous system and regeneration of the optic nerve in adult zebrafish. Glia. 60(2): 253-70, 2012.

Milanese, C., Sager, J. J., Bai, Q., Farrell, T. C., Cannon, J. R., Greenamyre, J. T., Burton, E. A. Hypokinesia and reduced dopamine levels in zebrafish lacking ß- and ?1-synucleins. J Biol Chem. 287(5): 2971-83, 2012. [Featured on the cover of the January 27, 2012 issue of JBC]

Sager, J.J., Torres, G.E., Burton, E. A. The zebrafish homologue of the human DYT1 dystonia gene is widely expressed in CNS neurons but non-essential for early motor system development. PLoS ONE. 7(9): e45175, 2012.

Cannon, J., Sew, T., Montero, L., Burton, E. A., and Greenamyre, J. T. Pseudotype-dependent lentiviral transduction of astrocytes or neurons in the rat substantia nigra. Experimental Neurology. 228(1), 41-52, 2011.

Van Laar, V. S., Arnold, B. A., Cassady, S. J., Chu, C. T., Burton, E. A., and Berman, S. B. Bioenergetics of neurons inhibit the translocation response of Parkin following rapid mitochondrial depolarization. Human Molecular Genetics. 20(5), 927-40, 2011.

Bai, Q., Sun, M., Stolz, D. B., Burton, E. A. The major isoform of zebrafish P0 is a 23.5kDa myelin glycoprotein expressed in selected white matter tracts of the central nervous system. Journal of Comparative Neurology. 519(8), 1580-96, 2011.

Horowitz, M., Milanese, C., Di Maio, R. Hu, X., Montero, L. M., Sanders, L., Tapias, V., Sepe, S., van Cappellen, G., Burton, E. A., Greenamyre, J. T., Matsroberardino, P. G. Single-cell redox imaging demonstrates a distinctive response of dopaminergic neurons to oxidative insults. Antioxidants & Redox Signaling. 15(4), 855-71, 2011.

Cario, C. L., Farrell, T. C., Milanese, C. and Burton, E. A. Automated measurement of zebrafish larval movement. The Journal of Physiology. 589(15), 3703-8, 2011.

Farrell, T. C., Cario, C. L., Milanese, C., Vogt, A., Jeong, J.-H., Burton, E. A. Evaluation of spontaneous propulsive movement as a screening tool to detect rescue of Parkinsonism phenotypes in zebrafish models. Neurobiology of Disease. 44(1), 9-18, 2011. [Featured on the cover of the October 2011 issue of NBD]

Bai, Q. and Burton, E.A. Cis-acting elements responsible for dopaminergic neuron-specific expression of zebrafish slc6a3 (dopamine transporter) in vivo are located remote from the transcriptional start site. Neuroscience. 164(3): 1138-51, 2009. PMID: 19755139

Bai, Q., Wei, X. and Burton, E.A. Expression of a 12-kb promoter element derived from the zebrafish enolase-2 gene in the zebrafish visual system. Neurosci Lett. 449(3): 252-7, 2009. PMID: 19007858

Bai, Q., Garver, J.A., Hukriede, N.A. and Burton, E.A. Generation of a transgenic zebrafish model of Tauopathy using a novel promoter element derived from the zebrafish eno2 gene. Nucleic Acids Res. 35(19): 6501-16, 2007. PMID: 17897967