Edward A Burton, MD DPhil

Assistant Professor, Neurology, Microbiology and Molecular Genetics

Contact

7015 Biomedical Science Tower-3
412-648-9720
F: 412-648-8537
eab25@pitt.edu
Website >

Focus

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.

Publications

Live imaging of mitochondrial dynamics in CNS dopaminergic neurons in vivo demonstrates early reversal of mitochondrial transport following MPP(+) exposure. Dukes AA, Bai Q, Van Laar VS, Zhou Y, Ilin V, David CN, Agim ZS, Bonkowsky JL, Cannon JR, Watkins SC, Croix CM, Burton EA, Berman SB. Neurobiol Dis. 2016 Nov;95:238-49. doi: 10.1016/j.nbd.2016.07.020. PMID: 27452482
 
α-Synuclein binds to TOM20 and inhibits mitochondrial protein import in Parkinson's disease.
Di Maio R, Barrett PJ, Hoffman EK, Barrett CW, Zharikov A, Borah A, Hu X, McCoy J, Chu CT, Burton EA, Hastings TG, Greenamyre JT.
Sci Transl Med. 2016 Jun 8;8(342):342ra78. doi: 10.1126/scitranslmed.aaf3634. PMID: 27280685 
 
The Developmental Toxicity of Complex Silica-Embedded Nickel Nanoparticles Is Determined by Their Physicochemical Properties.
Mahoney S, Najera M, Bai Q, Burton EA, Veser G.
PLoS One. 2016 Mar 31;11(3):e0152010. doi: 10.1371/journal.pone.0152010. PMID: 27031643 
 
The effect of blur on cortical responses to global form and motion.
Burton EA, Wattam-Bell J, Rubin GS, Atkinson J, Braddick O, Nardini M.
J Vis. 2015;15(15):12. doi: 10.1167/15.15.12. PMID: 26605841 
 
RAF inhibitors that evade paradoxical MAPK pathway activation. Zhang C, Spevak W, Zhang Y, Burton EA, Ma Y, Habets G, Zhang J, Lin J, Ewing T, Matusow B, Tsang G, Marimuthu A, Cho H, Wu G, Wang W, Fong D, Nguyen H, Shi S, Womack P, Nespi M, Shellooe R, Carias H, Powell B, Light E, Sanftner L, Walters J, Tsai J, West BL, Visor G, Rezaei H, Lin PS, Nolop K, Ibrahim PN, Hirth P, Bollag G. Nature. 2015 Oct 22;526(7574):583-6. doi: 10.1038/nature14982. PMID: 26466569
 
Glucocerebrosidase 1 deficient Danio rerio mirror key pathological aspects of human Gaucher disease and provide evidence of early microglial activation preceding alpha-synuclein-independent neuronal cell death. Keatinge M, Bui H, Menke A, Chen YC, Sokol AM, Bai Q, Ellett F, Da Costa M, Burke D, Gegg M, Trollope L, Payne T, McTighe A, Mortiboys H, de Jager S, Nuthall H, Kuo MS, Fleming A, Schapira AH, Renshaw SA, Highley JR, Chacinska A, Panula P, Burton EA, O'Neill MJ, Bandmann O. Hum Mol Genet. 2015 Dec 1;24(23):6640-52. doi: 10.1093/hmg/ddv369. PMID: 26376862 
 
Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor.
Tap WD, Wainberg ZA, Anthony SP, Ibrahim PN, Zhang C, Healey JH, Chmielowski B, Staddon AP, Cohn AL, Shapiro GI, Keedy VL, Singh AS, Puzanov I, Kwak EL, Wagner AJ, Von Hoff DD, Weiss GJ, Ramanathan RK, Zhang J, Habets G, Zhang Y, Burton EA, Visor G, Sanftner L, Severson P, Nguyen H, Kim MJ, Marimuthu A, Tsang G, Shellooe R, Gee C, West BL, Hirth P, Nolop K, van de Rijn M, Hsu HH, Peterfy C, Lin PS, Tong-Starksen S, Bollag G.N Engl J Med. 2015 Jul 30;373(5):428-37. doi: 10.1056/NEJMoa1411366. PMID: 26222558 
 
shRNA targeting α-synuclein prevents neurodegeneration in a Parkinson's disease model.
Zharikov AD, Cannon JR, Tapias V, Bai Q, Horowitz MP, Shah V, El Ayadi A, Hastings TG, Greenamyre JT, Burton EA.
J Clin Invest. 2015 Jul 1;125(7):2721-35. doi: 10.1172/JCI64502. PMID: 26075822 
 
Targeting cells of the myeloid lineage attenuates pain and disease progression in a prostate model of bone cancer.
Thompson ML, Jimenez-Andrade JM, Chartier S, Tsai J, Burton EA, Habets G, Lin PS, West BL, Mantyh PW.
Pain. 2015 Sep;156(9):1692-702. doi: 10.1097/j.pain.0000000000000228. PMID: 25993548 
 
Characterizing and Overriding the Structural Mechanism of the Quizartinib-Resistant FLT3 "Gatekeeper" F691L Mutation with PLX3397.
Smith CC, Zhang C, Lin KC, Lasater EA, Zhang Y, Massi E, Damon LE, Pendleton M, Bashir A, Sebra R, Perl A, Kasarskis A, Shellooe R, Tsang G, Carias H, Powell B, Burton EA, Matusow B, Zhang J, Spevak W, Ibrahim PN, Le MH, Hsu HH, Habets G, West BL, Bollag G, Shah NP.
Cancer Discov. 2015 Jun;5(6):668-79. doi: 10.1158/2159-8290.CD-15-0060. PMID: 25847190