Ethan Hughes Anschutz Cell Developmental Biology

Ethan Hughes (Ph.D.)


Department of Cell & Developmental Biology


Oligodendrocytes and their Precursors in the Adult Central Nervous System

Assistant Professor

Ph.DUniversity of Pennsylvania, 2009

ethan.hughes@cuanschutz.edu
Phone: (303) 724.3122
Fax: (303) 724.3420

12801 E 17th Ave.
Mail Stop 8108
Aurora, CO 80045

Graduate Program Affiliations

CSD
Cell Biology, Stem Cells and Development

Molecular Biology Program

Neuroscience Graduate Program

Medical Scientist Training Program

 

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In vivo-imagin​g of differentiation of an oligodendrocyte precursor cell over 10 days. 

Neuron-glia interactions in the adult CNS​​ 

The long-term goals of our work is to understand how neuron-glial interactions modulate brain function and contribute to pathology in neurodegenerative disease. Towards this goal, we study the interactions of oligodendrocyte lineage cells with neurons in the adult cerebral cortex.

Oligodendrocytes are the myelin-forming cells of CNS and their ensheathment of axons is essential for rapid synaptic communication. Oligodendrocyte dysfunction results in a diverse group of pediatric and adult disorders, most notably, X-linked adrenoleukodystrophy and multiple sclerosis. However, our understanding of the functions of oligodendrocytes and their precursors remains in its infancy. We use advanced imaging and cell-specific genetic manipulations to explore dynamic changes in neurons and glial cells in the living adult brain using long-term two-photon in vivo imaging, optogenetics, genetically encoded calcium indicators, and transcriptomics.

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Colorized montage of in vivo imaging of the response of an individual oligodendrocyte precursor cell responding to a CNS injury (white) over 30 days.Classification of individual myelin sheaths of oligodendrocytes in a 125 micron cubed volume of layer I of cortex acquired via in vivo imaging.

 

 

 

Latest Publications in PubMedGoogle ScholarORCID


Publications as of December 2020~

Bacmeister CM*, Barr HJ*, McClain CR*, Thornton MA, Nettles D, Welle CG, Hughes EG. (2020) Motor Learning Promotes Remyelination via New and Surviving Oligodendrocytes.

Nature Neuroscience. 23, 819–831.

Thornton, MA, Hughes, EG. (2020) Neuron-Oligodendroglia Interactions: Activity-Dependent Regulation of Cellular Signaling. Neuroscience Letters. 727, 134916.

Bacmeister CM*, Barr HJ*, McClain CR*, Nettles D, Thornton MA, Welle CG, Hughes EG. (2020) Motor Learning Promotes Remyelination via New and Surviving Oligodendrocytes. In press, Nature Neuroscience. bioRxiv. doi: https://doi.org/10.1101/2020.01.28.923656

Thornton, MA, Hughes, EG. (2020) Neuron-Oligodendroglia Interactions: Activity-Dependent Regulation of Cellular Signaling. In Press, Neuroscience Letters.

Miller SJ, Philips T, Kim N, Chen Z, Pham JT, Hughes EG, Sattler R, Ostrow, LW, Suk JS, Hanes J, Bergles DE, Robinson MB, Rothstein JD. (2018) Molecularly defined cortical astroglia subpopulation modulates neurons via secretion of Norrin. Nature Neuroscience. 22: 741–752. 

Benichoux V, Ferber AT, Hunt SD, Hughes EG, Tollin DJ. (2018) Across species ‘natural ablation’ study reveals the brainstem source for a non-invasive biomarker for binaural hearing. Journal of Neuroscience 38(40): 8563-8573.

Ozbay BN, Futia GL, Ma M, Bright VM, Gopinath JT, Hughes EG, Restrepo D, Gibson EA. (2018) Three dimensional two-photon imaging of neural activity in freely moving mice with a head mounted miniature fiber coupled microscope. bioRxiv 226431; doi: https://doi.org/10.1101/22643. Scientific Reports 8: 8108.

Hughes EG#*, Orthmann-Murphy JL*, Langseth AJ, Bergles DE#. (2018) Myelin remodeling and experience-dependent oligodendrogenesis persist in the middle-aged brain. Nature Neuroscience. 21: 696-706.  #Co-corresponding author.

Kim J, Hughes EG, Shetty AS, Arlotta P, Goff LA, Bergles DE, and Brown SP (2017) Changes in the excitability of neocortical neurons in a mouse model of amyotrophic lateral sclerosis are not specific to corticospinal neurons and are modulated by advancing disease. Journal of Neuroscience, in press.

Agarwal A, Wu P-H, Hughes EG, Fukaya M, Tischfield MA, Langseth AJ, Wirtz D, Bergles DE. (2017) Transient opening of the mitochondrial permeability transition pore induces microdomain calcium transients in astrocyte processes. Neuron 93: 587-605.

​​Hughes EG, Appel B. (2016) The cell biology of CNS myelination. Current Opinions Neurobiology 39:93-100....​

​​Hughes EG, Appel B. (2016) The cell biology of CNS myelination. Current Opinions Neurobiology 39:93-100.

Peng X, Hughes EG, Moscato EH, Parsons TD, Dalmau J, Balice-Gordon RJ. (2015) Cellular plasticity induced by anti-AMPA receptor encephalitis antibodies. Annals of Neurology 77: 381-98.​

Hughes EG*, Kang SH*, Fukaya M*, Bergles DE. (2013) Oligodendrocyte progenitors balance growth and self-repulsion to maintain homeostasis in the adult brain. Nature Neuroscience 16: 668–676.

Hughes EG*, Peng X*, Gleichman AJ, Lai M, Zhou L, Lynch DR, Dalmau J, Balice-Gordon RJ. (2010) Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis.  Journal of Neuroscience 30:  5866-5875.

Hughes EG, Elmariah SB, Balice-Gordon RJ.  (2010) Astrocyte secreted proteins selectively increase hippocampal GABAergic axon length, branching, and synaptogenesis. Molecular Cellular Neuroscience 43: 136-45.

Lancaster E*, Lai M*, Peng X, Hughes EG, Constantinescu R, Raizer J, Friedman D, Skeen M, Grisold W, Kimura A, Ohta K, Iizuka T, Graus F, Moss SJ, Balice-Gordon RJ, Dalmau J. (2010) The GABA (B) Receptor is a Novel Autoantigen of Limbic Encephalitis with Prominent Seizures. Lancet Neurology 9:  67-76.

Lai M*, Hughes EG*, Peng X*, Zhou L, Gleichman AJ, Shu H, Mata S, Kremens D, Vitaliani R, Geschwind MD, Bataller L, Kalb RG, Davis R, Graus F, Lynch DR, Balice-Gordon RJ, Dalmau J. (2009) AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Annals of Neurology 65: 424-34.

Keene SD*, Greco TM*, Parastatidis I, Lee SH, Hughes EG, Balice-Gordon RJ, Speicher DW and Ischiropoulos H. (2009) Mass spectrometric and computational analysis of cytokine-induced alterations in the astrocyte secretome. Proteomics 3: 768-82.

Dalmau J, Gleichman AJ*, Hughes EG*, Rossi JE, Peng X, Lai M, Deassain S, Rosenfeld MR, Balice-Gordon RJ, Lynch DR.  (2008) Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurology. 12:1091-8.

Kayser MS, McCelland AC, Hughes EG, Dalva MB. (2006) Intra-cellular and trans-synaptic regulation of glutamatergic synaptogenesis by EphB receptors.  Journal of Neuroscience 26:  12152-64.

Elmariah SB, Oh EJ, Hughes EG, Balice-Gordon RJ. (2005) Astrocytes regulate inhibitory synapse formation via Trk-mediated modification of postsynaptic GABAA receptors.  Journal of Neuroscience 25: 3638-50.

Hughes EG, Maguire JL, McMinn MT, Scholz RE, Sutherland ML. (2004) Loss of glial fibrillary acidic protein results in decreased glutamate transport and inhibition of PKA-induced EAAT2 cell surface trafficking.  Brain Res. Mol. Brain Res. 124: 114-23