Michael Byrne Robinson, Ph.D.
Division of Developmental and Behavioral Pediatrics
34th and Civic Center Boulevard
Philadelphia, PA 19104-4318
Fax: (215) 590-3779
Lab: (215) 590-3839
Bates College , 1980.
University of Minnesota, 1985.
Description of Research ExpertiseRESEARCH INTERESTS
Signaling pathways that regulate glutamate transporters and the relationship of these transporters to acute brain injury
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.
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 Publications109. 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.