
FACULTY
Jeffrey D. Erickson, PhD
Professor of Neuroscience, Pharmacology, and Experimental Therapeutics
Pharmacology
- jerick@lsuhsc.edu
- Medicine
Academic Office:
LSUHSC School of Medicine
Neuroscience Center of Excellence
2020 Gravier St.
New Orleans, LA 70112
Phone: (504) 599-0845
Fax: (504) 599-0488
Bio
2021 - Present: Professor of Pharmacology and Neuroscience, Neuroscience Center of Excellence, LSU Health Sciences Center, New Orleans, LA.
2002 - 2021: Associate Professor of Pharmacology and Neuroscience, Neuroscience Center of Excellence, LSU Health Sciences Center, New Orleans, LA
1997 - 2002: Assistant Professor of Pharmacology and Neuroscience, Neuroscience Center of Excellence, LSU Health Sciences Center, New Orleans, LA
1993 - 1997: Postdoc, Laboratory of Cell Biology, NIMH, Bethesda, MD
Education
1992: Ph.D. (Genetics), George Washington University, Washington, DC
1984: M.Sc. (Pharmaceutical Sciences), University of Colorado, Boulder, CO
1981: B.A. (Molecular, Cellular, and Developmental Biology), University of Colorado, Boulder, CO
Selected Publications
- Kyllo, T., Allocco, D., Hei, L.V., Wulff, H., and Erickson, J.D. (2024) Riluzole attenuates acute neural injury and reactive gliosis, hippocampal-dependent
cognitive impairments and spontaneous recurrent generalized seizures in a rat model
of temporal lobe epilepsy. Front. Pharmacol. Oct 30:15:1466953
- Erickson, J.D., Kyllo. T, and Wulff, H. (2023) Ca2+-regulated expression of high affinity methylaminoisobutyric acid transport in
hippocampal neurons inhibited by riluzole and novel neuroprotective aminothiazoles. Curr. Res. Physiol. 6: 100109
- Kyllo, T., Singh, V., Shim, H., Latika, S., Nguyen, H.M., Chen, Y.-J., Terry, E.,
Wulff, H., and Erickson, J.D. (2023) Riluzole and novel naphthalenyl substituted aminothiazole derivatives prevent acute
neural excitotoxic injury in a rat model of temporal lobe epilepsy. Neuropharmacology 224: 109349
- Pietrancosta, N., Djibo, M., Daumas, S., El Mestikawy, S., and Erickson J.D. (2020) Molecular, structural, functional and pharmacological sites for vesicular glutamate
transporter regulation. Mol. Neurobiol. 30, 1-25.
- Erickson, J.D. (2017) Functional identification of activity-regulated high-affinity glutamine transport
in hippocampal neurons inhibited by riluzole. J. Neurochem. 142, 29-40.
- Jin, L.W., Horiuchi, M., Wulff, H., Liu, X.B., Cortopassi, G.A. and Erickson, J.D. and Maezawa, I. (2015) Dysregulation of glutamine transporter SNAT1 in Rett syndrome microglia: a mechanism
for mitochondrial dysfunction and neurotoxicity. J. Neurosci. 35, 2516-2529.
- He, H., Mahnke, A.H., Doyle, S. Fan, N., Wang, D.D., Hall, B.J., Tang, Y.P., Inglis,
F.M., Chen, C., and Erickson, J.D. (2012) Neurodevelopmental role for VGLUT2 in pyramidal neuron plasticity, dendritic refinement,
and in spatial learning. J. Neurosci. 32, 15886-15901.
- Doyle, S., Pyndiah, S., De Gois, S., and Erickson, J.D. (2010) Excitation-transcription coupling via calcium/calmodulin-dependent protein kinase/ERK1/2
signaling mediates the coordinate induction of VGLUT2 and Narp triggered by a prolonged
increase in glutamatergic synaptic activity. J. Biol. Chem. 285, 14366-14376.
- Grewal, S., Defamie, N., Zhang, X., De Gois, S., Shawki, A., Mackenzie, B., Chen,
C., Varoqui, H., and Erickson, J.D. (2009) SNAT2 amino acid transporter is regulated by amino acids of the SLC6 GABA transporter
subfamily in neocortical neurons and may play no role in delivering glutamine for
glutamatergic transmission. J. Biol. Chem. 284, 11224-11236.
- Evans, K., Nasim, Z., Brown, J., Butler, H., Kauser, S., Varoqui, H., Erickson, J.D., Herbert, T.P., and Bevington, A. (2007) Acidosis-sensing glutamine pump SNAT2 determines amino acid levels and mammalian target
of rapamycin signaling to protein synthesis in L6 muscle cells. J. Am. Soc. Nephrol. 18, 1426-1436.
- Burkhalter, J., Fiumelli, H, Erickson, J.D., and Martin, J.L. (2007) A critical role for system A amino acid transport in the regulation of dendritic development
by BDNF. J. Biol. Chem. 282, 5152-5159.
- Erickson, J.D., De Gois, S., Varoqui, H., Schafer, M.K., and Weihe, E. (2006) Activity-dependent regulation of vesicular glutamate and GABA transporters: a means
to scale quantal size. Neurochem. Int. 48, 643-649.
- Melone, M., Varoqui, H., Erickson, J.D., and Conti, F. (2006) Localization of the Na(+)-coupled neutral amino acid transporter 2 in the cerebral
cortex. Neuroscience 140, 281-292.
- De Gois, S., Jeanclos, E., Morris, M., Grewal, S., Varoqui, H., and Erickson, J.D. (2006) Identification of endophilins 1 and 3 as selective binding partners for VGLUT1 and
their co-localization in neocortical glutamatergic synapses: implication for vesicular
glutamate transporter trafficking and excitatory vesicle formation. Cell. Mol. Neurobiol. 26, 677-691.
- Wilson, N.R., Kang, J., Hueske, E.V., Leung, T., Varoqui, H., Murnick, J.G., Erickson, J.D., and Liu, G. (2005) Presynaptic regulation of quantal size by VGLUT1. J. Neurosci. 25, 6221-6234.
- De Gois, S., Schafer, M.K., Defamie, N., Chen, C., Ricci, A., Weihe, E., Varoqui,
H., and Erickson, J.D. (2005) Homeostatic scaling of vesicular glutamate and GABA transporter expression in rat
neocortical circuits. J. Neurosci. 25, 7121-7133.
- Melone, M., Quagliano, F., Barbaresi, P., Varoqui, H., Erickson, J.D., and Conti. F. (2004) Localization of the glutamine transporter SNAT1 in rat cerebral cortex and neighboring
structures, with a note on its localization in human cortex. Cereb. Cortex 14, 562-574.
- Mackenzie, B., and Erickson, J.D. (2004) Sodium-coupled neutral amino acid (System N/A) transporters of the SLC38 gene family. Pflugers Arch. 447, 784-795.
- Mackenzie, B., Schäfer, M.K.-H., Erickson, J.D., Hediger, M.A., Weihe, E., and Varoqui, H. (2003) Functional properties and cellular distribution of the system A glutamine transporter
SNAT1 support specialized roles in central neurons. J. Biol. Chem. 278, 23720-29730.
- Schäfer, M.K.-H., Varoqui, H., Defamie, N., Weihe, E., and Erickson, J.D. (2002) Molecular cloning and functional identification of mouse vesicular glutamate transporter
3 and its expression in subsets of novel excitatory neurons. J. Biol. Chem. 277, 50734-50748.
- Varoqui, H., Schäfer, M.K.-H. Zhu, H., Weihe, E., and Erickson, J.D. (2002) Identification of the differentiation-associated Na+/Pi transporter as a novel vesicular
glutamate transporter expressed in a distinct set of glutamatergic synapses. J. Neurosci. 22, 142-155.
- Armano, S., Coco, S., Bacci, A., Pravettoni, E., Schenk, U., Verderio, C., Varoqui,
H., Erickson, J.D., and Matteoli, M. (2002) Localization and functional relevance of system A neutral amino acid transporters
in cultured hippocampal neurons. J. Biol. Chem. 277, 10467-10473.
- Yao, D., Mackenzie, B., Ming, H., Varoqui, H., Zhu, H., Hediger, M.A. and Erickson, J.D. (2000) A novel system A isoform mediating Na+/neutral amino acid cotransport. J. Biol. Chem. 275, 22790-22797.
- Varoqui, H., Zhu, H., Yao, D., Ming, H., and Erickson, J.D. (2000) Cloning and functional identification of a neuronal glutamine transporter. J. Biol. Chem. 275, 4049-4054.
- Erickson, J.D. and Varoqui, H. (2000) Molecular analysis of vesicular amine transporter function and targeting to secretory
organelles. FASEB J. 14, 2450-2458.
- Miller, G.W., Erickson, J.D., Perez, J.T, Penland, S.N., Mash, D.C., Rye, D.B. and Levey, A.I. (1999) Immunochemical analysis of vesicular monoamine transporter VMAT2 protein in Parkinson’s
disease. Exp Neurol. 156, 138-148.
- Gilmor, M.L., Erickson, J.D., Varoqui, H., Hersh, L.B., Bennett, D., Cochran, L., Mufson, E.J., and Levey, A.I.
(1999) Preservation of nucleus basalis neurons containing choline acetyltransferase and the
vesicular acetylcholine transporter in the elderly with mild cognitive impairment
and early Alzheimer’s disease. J. Comp. Neurol. 411, 693-704.
- Varoqui, H., and Erickson, J.D. (1998) The cytoplasmic tail of the vesicular acetylcholine transporter contains a synaptic
vesicle targeting signal. J. Biol. Chem. 273, 9094-9098.
- Varoqui, H. and Erickson J.D. (1997) Vesicular neurotransmitter transporters: potential sites for the regulation of synaptic
function. Mol. Neurobiol. 15, 165-191.
- Weihe, E., Tao-Cheng, J.-H., Schäfer, M.K.-H., Erickson, J.D., and Eiden. L.E. (1996) Visualization of the vesicular acetylcholine transporter in cholinergic nerve terminals
and its targeting to a specific population of small synaptic vesicles. Proc. Natl. Acad. Sci. 93, 3547-3552.
- Bjoras, M., Gjesdal, O., Erickson, J.D., Torp, R., Levy, L.M., Ottersen, O.P., Degree, M., Storm-Mathisen, J., Seeberg, E.,
Danbolt, N.C. (1996) Cloning and expression of a neuronal rat brain glutamate transporter. Mol. Brain Res. 36: 163-168.
- Erickson, J.D., Schäfer, M.K.-H., Bonner, T.I., Eiden, L.E. and Weihe, E. (1996) Distinct pharmacological properties and distribution in neurons and endocrine cells
of two isoforms of the human vesicular monoamine transporter. Proc. Natl. Acad. Sci. 93, 5166-5171.
- Usdin, T.B., Eiden, L.E., Bonner, T.I. and Erickson, J.D. (1995) Molecular biology of the vesicular ACh transporter (VAChT). Trends in Neurosci. 18: 218-224.
- Erickson, J.D., Eiden, L.E., Schäfer, M.K.-H. and Weihe, E. (1995) Reserpine- and tetrabenazine- sensitive transport of 3H-histamine by the neuronal
isoform of the vesicular monoamine transporter. J. Mol. Neurosci. 6: 277-287.
- Varoqui, H., Diebler, M.-F., Meunier, F.-M., Rand, J.B., Usdin, T.B., Bonner, T.I.,
Eiden, L.E. and Erickson, J.D. (1994) Cloning and expression of the vesamicol binding protein from the marine ray Torpedo:
homology with the putative vesicular acetylcholine transporter UNC-17 from Caenorhabditis
elegans. FEBS Lett. 342: 97-102.
- Schäfer, M.K.-H., Weihe, E., Varoqui, H., Eiden, L.E. and Erickson, J.D. (1994) Distribution of the vesicular acetylcholine transporter (VAChT) in the central and
peripheral nervous systems of the rat. J. Mol. Neurosci. 5: 1-26.
- Erickson, J.D., Varoqui, H., Schäfer, M.K.-H., Modi, W., Diebler, M.-F., Weihe, E., Rand, J.B.,
Eiden, L.E., Bonner, T.I. and Usdin, T.B. (1994) Functional identification of a vesicular acetylcholine transporter and its expression
from a 'cholinergic' gene locus. J. Biol. Chem. 269: 21929-21932.
- Erickson, J.D. and Eiden, L.E. (1993) Functional identification and molecular cloning of a human brain vesicle monoamine
transporter. J. Neurochem. 61: 2314-2317.
- Erickson, J.D., Eiden, L.E. and Hoffman, B.J. (1992) Expression cloning of a reserpine-sensitive vesicular monoamine transporter. Proc. Natl. Acad. of Sci. 89: 10993-10997.
- Erickson, J.D., Masserano, J.M., Barnes, E., Ruth, J.A. and Weiner, N. (1990) Chloride ion increases 3H-dopamine accumulation by synaptic vesicles purified from rat striatum: inhibition by thiocyanate ion. Brain Res. 516: 155-160.
Research
Interests
Keywords:
vesicular neurotransmitter transporters, neuronal glutamine transporters,
excitotoxicity, neuroprotective agents, epileptogenesis, cognitive impairment
Current Research
Novel presynaptic agents to prevent excitotoxic neural injury
Excessive presynaptic glutamatergic transmission is thought to be involved in various human brain disorders that result in glutamate (Glu) excitotoxicity, reactive gliosis and neuroinflammation such as epilepsy and Alzheimer’s disease. Glutamatergic transmission requires the transport of cytoplasmic Glu into synaptic vesicles before its release from axon terminals by Ca2+ -dependent exocytosis. Our prior work has established that for mammalian synaptic vesicles that express VGLUT1, quantal size can be regulated by the number of transporters per vesicle or the concentration of Glu in the cytoplasm available for vesicular loading. Under normal conditions, Krebs cycle intermediates can sustain axon terminal cytoplasmic Glu levels and vesicular Glu stores for release. However, acute or chronic hyper-glutamatergic activity may require import of glutamine (Gln) into axon terminals from glia to maintain cytoplasmic and vesicular Glu stores for release. Activity-induced modulation of synaptic efficacy and glutamatergic epileptiform activity is significantly reduced by application of 2-(methylamino)isobutyrate (MeAIB), a competitive and reversible inhibitor of the sodium-coupled Gln transporter (SNAT; system A) subtypes 1 and 2. However, SNAT1 and SNAT2 are excluded from axon terminals, suggesting that an unidentified neuronal MeAIB/Gln transporter(s) may be involved to sustain glutamatergic transmission under conditions of increased activity.
We have functionally identified a neural activity-regulated MeAIB/Gln transport system in primary hippocampal cultures that is inhibited by riluzole, an anticonvulsant agent that can reduce synaptic release of Glu and excitotoxic injury by multiple mechanisms. We recently reported that riluzole attenuates acute neural injury and reactive gliosis, hippocampal-dependent cognitive impairments and spontaneous recurrent generalized seizures in a rat model of temporal lobe epilepsy (TLE). This suggests that riluzole has significant potential as an antiepileptogenic drug in the clinical setting after an acute seizure event to prevent the development of epilepsy. Since riluzole has untoward effects (sleepiness, mental slowing), we screened benzothiazole and aminothiazole chemical libraries to identify compounds that possess the ability to inhibit neural activity-regulated MeAIB/Gln transport as potently as riluzole, but are structurally unique. Based upon these screens, we have synthesized several novel naphthalenyl substituted aminothiazoles (e.g., SKA-378) that potently inhibit neural activity-regulated MeAIB/Gln transport at the plasma membrane in vitro, like riluzole, and are neuroprotective. SKA-378 exhibits excellent 'drug-like' properties with high oral availability and good brain penetration. Interestingly, while SKA-378 could not prevent kainic acid (KA)-induced status-epilepticus like riluzole, SKA-378 prevents hippocampal neural injury and reactive gliosis following KA-induced SE. Our goal is to understand the common mechanism of neuroprotection by riluzole and SKA-378 that may be important to attenuate the progression of excitotoxic brain diseases such as epilepsy and Alzheimer’s disease.