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Michael Byrne Robinson, Ph.D.

Michael Byrne Robinson, Ph.D.

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Professor of Pediatrics
Department: Pediatrics
Graduate Group Affiliations

Contact information
Abramson Research Center, Rm 502D
Division of Developmental and Behavioral Pediatrics
34th and Civic Center Boulevard
Philadelphia, PA 19104-4318
Office: (215) 590-2205
Fax: (215) 590-3779
Lab: (215) 590-3839
Education:
B.S. (Chemistry)
Bates College , 1980.
Ph.D. (Biochemistry)
University of Minnesota, 1985.
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Description of Research Expertise

RESEARCH INTERESTS
Signaling pathways that regulate glutamate transporters and the relationship of these transporters to acute brain injury

RESEARCH TECHNIQUES
Biochemical, cell biological, and molecular biological techniques. These include cell culture and transfection of cDNAs, construction of chimeric and mutant transporters, assays for activation of signaling pathways, measurement of transport activity, quantitation of cell surface expression of transporters, western blotting, confocal microscopy, high performance liquid chromatography, and assessment of cell death.

RESEARCH SUMMARY
Glutamate and aspartate are the predominant excitatory neurotransmitters in the mammalian CNS. These two excitatory amino acids (EAAs) mediate most of the rapid depolarization that occurs in the CNS. In fact, the levels of these transmitters are 1000- to 10,000-fold higher than those of many other important neurotransmitters, including dopamine, serotonin, and acetylcholine. Paradoxically, these EAAs are also potent neurotoxins, both in vivo and in vitro. In fact, excessive activation of EAA receptors contributes to the neuronal degeneration observed after acute insults to the CNS, such as stroke and head trauma. We are interested in the normal physiology of EAAs and the role of these transmitters in neurodegeneration. Our laboratory has focused on understanding the regulation of extracellular levels of EAAs because it is this pool of EAAs that is toxic to neurons. Extracellular concentrations of glutamate and aspartate are normally maintained in the low micromolar range by a family of sodium-dependent high affinity transporters that are present on both neurons and glial cells. Our laboratory has developed evidence that neurons induce and maintain expression of one of the astrocytic transporters critical for limiting excitotoxicity. We have begun to define the mechanisms that contribute to this regulation. Our laboratory has also found that the function of several of the transporter subtypes can be rapidly (within minutes) altered by activation of certain kinases. This regulation is associated with a redistribution of these transporters to/or from the plasma membrane (see the image below). The long term goal of the laboratory is to develop new strategies for limiting glutamate-mediated damage by understanding the endogenous mechanisms that clear this excitotoxin.

Selected Publications

Jackson J.G. and Robinson M.B. : Reciprocal regulation of mitochondrial dynamics and calcium signaling in astrocyte processes. Journal of Neuroscience 35: 15199-213, 2015.

Jackson M.B., O’Donnell J.C., Krizman E., and Robinson M.B. : Displacing hexokinase from mitochondrial voltage-dependent anion channel impairs GLT1-mediated glutamate uptake but does not disrupt interactions between GLT-1 and mitochondrial proteins. Journal of Neuroscience Research 93: 999-1008, 2015.

Raju Karthik, Doulias Paschalis-Thomas, Evans Perry, Krizman Elizabeth N, Jackson Joshua G, Horyn Oksana, Daikhin Yevgeny, Nissim Ilana, Yudkoff Marc, Nissim Itzhak, Sharp Kim A, Robinson Michael B, Ischiropoulos Harry: Regulation of brain glutamate metabolism by nitric oxide and S-nitrosylation. Science signaling 8(384): ra68, 2015.

Ghosh Mausam, Lane Meredith, Krizman Elizabeth, Sattler Rita, Rothstein Jeffrey D, Robinson Michael B: Transcription Factor Pax6 Contributes to Induction of GLT-1 Expression in Astrocytes Through an Interaction with a Distal Enhancer Element. Journal of neurochemistry doi: 10.1111/jnc.13406, 2015.

Jackson J.G., O’Donnell J.C., Takano H., Coulter D.A., and Robinson M.B.: Neuronal activity and glutamate uptake decrease mitochondrial mobility and position mitochondria near glutamate transporters. Journal of Neuroscience 34: 1613-1624, 2014.

Jager J., O'Brien W.T., Manlove J., Krizman, E.N., Fang B., Gerhart-Hines Z., Robinson M.B., and Lazar M.A.: Behavioral changes and dopaminergic dysregulation in mice lacking the nuclear receptor Rev-erbalpha. Molecular Endocrinology 28: 490-498, 2014.

Lane M.C., Jackson J.G., Krizman E.N., Rothstein J.D., Porter B.E., and Robinson M.B. : Genetic deletion of the neuronal glutamate transporter, EAAC1, results in decreased neuronal death after pilocarpine-induced status epilepticus. Neurochemistry International 73: 152-158, 2013.

Brendan S. Whitelaw and Michael B. Robinson: Inhibitors of glutamate dehydrogenase block sodium-dependent glutamate uptake in rat brain brain membranes. Frontiers in Endocrinology 4:123 doi:10.3389, 2013.

Bauer D.E., Jackson J.G., Genda E.N., Montoya M.M., Yudkoff M., and Robinson M.B.: The glutamate transporter, GLAST, participates in a macromolecular complex that supports glutamate metabolism. Neurochemistry International 61: 566-574, 2012.

Ross J.R., Porter B.E., Buckley P.T., Eberwine J.H., and Robinson M.B. : mRNA for the EAAC1 subtype of glutamate transporter is present in neuronal dendrites in vitro and dramatically increases in vivo after a seizure Neurochem. Int. 58: 366-375, 2011.

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Last updated: 01/06/2016
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