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Michael Byrne Robinson, Ph.D.
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Emeritus Professor of Pediatrics (Developmental and Behavioral Pediatrics)
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Member of the Institute for Neurological Sciences, University of Pennsylvania Medical School
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Director, Analytical Neurochemistry Core, Intellectual and Developmental Disabilities Research Center (IDDRC)
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Member, Children's Hospital of Philadelphia Research Institute
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Head Neuroscience Affinity Group, Children's Hospital of Philadelphia Research Institute
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Director (MPI), Intellectual and Developmental Disabilities Research Center
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Department: Pediatrics
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Contact information
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Abramson Research Center, Rm 502D
3b Division of Developmental and Behavioral Pediatrics
47 34th and Civic Center Boulevard
Philadelphia, PA 19104-4318
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3b Division of Developmental and Behavioral Pediatrics
47 34th and Civic Center Boulevard
Philadelphia, PA 19104-4318
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Office: (215) 590-2205
34 Fax: (215) 590-3779
34 Lab: (215) 590-3839
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34 Fax: (215) 590-3779
34 Lab: (215) 590-3839
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Publications
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Links
e8 Search PubMed for articles
91 Training Grant in Neurodevelopmental Disabilities
98 Neuroscience Graduate Group (NGG) Faculty Page
92 Pharmacology Graduate Group Faculty Page
ab The Intellectual and Developmental Disabilities Research Center (IDDRC) at CHOP/Penn
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e8 Search PubMed for articles
91 Training Grant in Neurodevelopmental Disabilities
98 Neuroscience Graduate Group (NGG) Faculty Page
92 Pharmacology Graduate Group Faculty Page
ab The Intellectual and Developmental Disabilities Research Center (IDDRC) at CHOP/Penn
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Education:
21 9 B.S. 16 (Chemistry) c
27 Bates College , 1980.
21 a Ph.D. 19 (Biochemistry) c
30 University of Minnesota, 1985.
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Permanent link21 9 B.S. 16 (Chemistry) c
27 Bates College , 1980.
21 a Ph.D. 19 (Biochemistry) c
30 University of Minnesota, 1985.
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80 Signaling pathways that regulate glutamate transporters and the relationship of these transporters to acute brain injury
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1b RESEARCH TECHNIQUES
1a9 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.
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18 RESEARCH SUMMARY
708 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.
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Description of Research Expertise
23 RESEARCH INTERESTS80 Signaling pathways that regulate glutamate transporters and the relationship of these transporters to acute brain injury
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1b RESEARCH TECHNIQUES
1a9 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.
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18 RESEARCH SUMMARY
708 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.
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1b6 109. Miller S.J., Philips T., Kim N., Dastgheyb R., Chen Z., Daigle J.G., Datta M., Pham J.T., Videndky S., Highes E.G., Robinson M.B., Sattler R., Tomer R., Suk J.S., Bergles D.E., Haughey N., Pletnikov M., Hanes J., and Rothstein J.D.: Molecularly defined cortical astroglia subpopulation modulates neurons via secretion of Norrin. Nature Neuroscience April 2019.
17b Port R.G., Gajewski C., Krizman E., Dow H.C., Hirano S., Brodkin E.S., Carlson G.C., Robinson M.B., Roberts T.P.L., and Siegel S.J. : Protocadherin10 alters oscillations, amino acid levels, and their coupling: Baclofen partially restores oscillatory defects. Neurobiology of Disease 108: 324-338. 2017.
e9 Lee M.C., Martinez-Lozado, Z., Krizman E., and Robinson M.B.: Endothelia induce expression of GLT-1 in astrocytes. Journal of Neurochemistry 143: 489-506, 2017.
13e 105. O’Donnell J.C., Jackson J.G., and Robinson M.B. : Transient oxygen glucose deprivation causes a delayed loss of mitochondria and increases spontaneous calcium signaling in astrocytic processes. Journal of Neuroscience 36: 7109-7127. 2016.
173 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, 2016.
1b1 Sengupta S., Yang G., O'Donnell J.C., Hinson M.D., McCormack S.E., Falk M.J., La P., Robinson M.B., Williams M.L., Yohannes M.T., Polyak E., Nakamaru-Ogiso E., and Dennery P.A: The circadian gene Rev-erbα improves cellular bioenergetics and provides preconditioning for protection against oxidative stress. Free Radical Biology and Medicine 93: 177-189. 2016.
16f 104. Wood K.H., Johnson B.S., Welsh S.A., Lee J.Y., Cui Y., Krizman E., Brodkin E.S., Blendy J.A., Robinson M.B., Bartolomei M.S., and Zhou Z. : Tagging methyl-CpG-binding domain proteins reveals different spatiotemporal expression and supports distinct functions. Epigenomics 8: 455-473. 2016.
17a 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.
198 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.
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Selected Publications
14f Jackson J.G., Krizman E., Takano H., Lee M., Choi G.C., Putt M.E., and Robinson M.B.: Activation of glutamate transport increase arteriole diameter in vivo: Implications for neurovascular coupling. Frontiers in Cell. Neurosci doi 10.3389/fncel.2022.831061, 2022.1b6 109. Miller S.J., Philips T., Kim N., Dastgheyb R., Chen Z., Daigle J.G., Datta M., Pham J.T., Videndky S., Highes E.G., Robinson M.B., Sattler R., Tomer R., Suk J.S., Bergles D.E., Haughey N., Pletnikov M., Hanes J., and Rothstein J.D.: Molecularly defined cortical astroglia subpopulation modulates neurons via secretion of Norrin. Nature Neuroscience April 2019.
17b Port R.G., Gajewski C., Krizman E., Dow H.C., Hirano S., Brodkin E.S., Carlson G.C., Robinson M.B., Roberts T.P.L., and Siegel S.J. : Protocadherin10 alters oscillations, amino acid levels, and their coupling: Baclofen partially restores oscillatory defects. Neurobiology of Disease 108: 324-338. 2017.
e9 Lee M.C., Martinez-Lozado, Z., Krizman E., and Robinson M.B.: Endothelia induce expression of GLT-1 in astrocytes. Journal of Neurochemistry 143: 489-506, 2017.
13e 105. O’Donnell J.C., Jackson J.G., and Robinson M.B. : Transient oxygen glucose deprivation causes a delayed loss of mitochondria and increases spontaneous calcium signaling in astrocytic processes. Journal of Neuroscience 36: 7109-7127. 2016.
173 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, 2016.
1b1 Sengupta S., Yang G., O'Donnell J.C., Hinson M.D., McCormack S.E., Falk M.J., La P., Robinson M.B., Williams M.L., Yohannes M.T., Polyak E., Nakamaru-Ogiso E., and Dennery P.A: The circadian gene Rev-erbα improves cellular bioenergetics and provides preconditioning for protection against oxidative stress. Free Radical Biology and Medicine 93: 177-189. 2016.
16f 104. Wood K.H., Johnson B.S., Welsh S.A., Lee J.Y., Cui Y., Krizman E., Brodkin E.S., Blendy J.A., Robinson M.B., Bartolomei M.S., and Zhou Z. : Tagging methyl-CpG-binding domain proteins reveals different spatiotemporal expression and supports distinct functions. Epigenomics 8: 455-473. 2016.
17a 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.
198 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.
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