Portal to the Penn Neuroscience Community
Home
MINS Members
MINS News
Weekly Events
MINS Colloquium Schedule
History
Community Outreach Programs
Neuroscience Graduate Group
Other Educational Activities
Society for Neuroscience
Classified Ads
MINS Members
Michael
Robinson, Ph.D.
Professor of Pediatrics
Depts of Pediatrics and Pharmacology
School of Medicine
Abramson Research Building, Rm 502
34th and Civic Center Boulevard/4318
(215) 590-2205 FAX: (215) 590-3779
email: robinson@pharm.med.upenn.edu
Click here for selected publications since Dr. Robinson's arrival at Penn
RESEARCH INTERESTS
Signaling pathways that regulate glutamate transporters and the relationship
of these transporters to acute brain injuryRESEARCH 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.
This confocal image is an optical cross section of a cell treated for 30 min with either an activator of protein kinase C (PMA) or an inhibitor of phosphatidylinositol 3-kinase (wort). The red staining represents the transporter and the cell nuclei are stained with DAPI (purple). This neuronal transporter is enriched in pyramidal cells of the hippocampus and cortex, two brain regions that are exquisitely sensitive to stroke.
