Michael
 
Byrne
 
Robinson
Ph.D.
Email: 
robinson@mail.med.upenn.edu
Address: 
Abramson Research Center, Rm 502D Division of Developmental and Behavioral Pediatrics 34th and Civic Center Boulevard
(215) 590-2205
Affiliations
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.

Appointments
Professor of Pediatrics at University of Pennsylvania School of Medicine (2008– present)
Research Professor of Pediatrics at University of Pennsylvania School of Medicine (2004 – 2007)
Professor of Pharmacology at University of Pennsylvania School of Medicine (2004– present)
Assistant Professor of Pharmacology at University of Pennsylvania School of Medicine (1988 – 1995)
Assistant Professor of Pediatrics at University of Pennsylvania School of Medicine (1988 – 1995)
Associate Professor of Pharmacology at University of Pennsylvania School of Medicine (1995 – 2004)
Research Associate Professor of Pediatrics at University of Pennsylvania School of Medicine (1995 – 2004)
Education
Ph.D., Biochemistry, University of Minnesota (1985)
B.S., Chemistry, Bates College (1980)
Selected Publications
González M.I., and Robinson M.B.. Neurotransmitter transporters: Why dance with so many partners?. Curr. Opin. in Pharm.. Vol 4. 2004:30-35.
Kalandadze A, Wu Y., Fournier K., and Robinson M.B.. Identification of motifs involved in endoplasmic reticulum retention/forward trafficking of the GLT-1 subtype of glutamate transporter. J. Neurosci.. Vol 24. 2004:5183-92.
González M.I., and Robinson M.B.. Phorbol myristate acetate-dependent interaction of protein kinase Cá and the neuronal glutamate transporter EAAC1. J. Neurosci. Vol 23. 2003:5589-5593.
Susarla B.T.S., and Robinson M.B.. Rottlerin, an inhibitor of protein kinase Cä, inhibits astrocytic glutamate transport activity and reduces GLAST immunoreactivity by a mechanism that appears to be PKCä independent. J. Neurochem.. Vol 86. 2003:635-645.
Crino P.B., Jin H., Robinson M.B., Coulter D., Brooks-Kayal A.. Increased expression of the neuronal glutamate transporter (EAAT3/EAAC1) in hippocampal and neocortical epilepsy. Epilepsia. Vol 43. 2002:211-218.
Raper S.E. Yudkoff M., Chirmule N., Gao G.P., Nunes F., Hashal Z.J., Furth E.E., Propert K.J., Robinson M.B., Maosin S., Simoes H., Speocher L., Highes J., Tazelaar J., Wivel N.A., Wilson J.M., and Batshaw M.L.. A pilot study of in vivo liver-directed gene transfer with an adenoviral vector in partial ornithine transcarbamylase deficiency. Human Gene Therapy. Vol 13. 2002:163-175.
Holt, D.E., Washabau R.J., Djali S., Dayrell-Hart B., Drobatz K., Heyes M.P., and Robinson M.B.. Cerebrospinal fluid glutamine, tryptophan, and tryptophan metabolite concentrations are altered in dogs with portosystemic shunts. JAMVA. Vol 63. 2002:1167-1171.
González M.I., Kazanietz M.G., and Robinson M.B.. Regulation of the neuronal glutamate transporter, excitatory amino acid carrier-1 (EAAC1), by different protein kinase C subtypes. Mol. Pharm.. Vol 62. 2002:901-910.
Kalandadze A., Wu Y., and Robinson M.B.. Protein kinase C activation decreases cell surface expression of the GLT-1 subtype of glutamate transporter: Requirement of a carboxy-terminal domain and partial dependence on serine-486. J. Biol. Chem.. Vol 277. 2002:45741-45750.
Robinson M.B.. Regulated trafficking of neurotransmitter transporters: Common notes but different melodies. J. Neurochem.. Vol 80. 2002:1-11.