Administration Basic Sciences Clinical Sciences Centers of Excellence
Department Title
Spotlight Section New Orleans
 

Laura Harrison, PhD 

Research Assistant Professor
of Pharmacology and Neuroscience

Neuroscience Center of Excellence and Department of Pharmacology

Louisiana State University Health Sciences Center
2020 Gravier Street
New Orleans, Louisiana 70112 

Phone: (504) 568-2057

e-mail: Lhar14@lsuhsc.edu

 

Figure 1. Schematic of Rhes interaction with DA receptor signaling cascades. Rhes is proposed to inhibit cAMP accumulation by D1 receptors, either by inhibiting Gαs/olf or activating Gαi/o. Also, Rhes may promote IP3 formation by one of two mechanisms: either directly, by increasing the coupling of DA receptors to Gαq/11 or indirectly, by preventing excess activation of the cAMP-PKA pathway from inhibiting this pathway.

http://www.medschool.lsuhsc.edu/faculty/docs/Laura Harrison 21st NS Retreat, revised.pdf

Degrees

1990: Loyola University, B.A. in Psychology

1998: Tulane University, Ph.D. in Neuroscience

1998-2001: Oregon Health and Science University, Postdoctoral Fellow

2001-2004: University of New Orleans, Postdoctoral Fellow

Bio

Awards/Recognitions/Lectures:

National Research Service Award Individual Predoctoral Fellowship

Chemical Rubber Company Freshman Chemistry Award

Clinical Interests

Current Research:

Several major human health disorders, such as schizophrenia and drug addiction, are known to involve dysregulation of dopamine (DA) systems. However, despite much progress in unraveling the mechanisms of DA signaling, many questions remain. One important issue is the question of how the balance of DA receptor signaling through various intracellular pathways is regulated. For example, DA receptors are now known to increase intracellular calcium through Gαq/11 coupling, in addition to the more well-studied action on adenylyl cyclase (AC) activity through coupling to Gαs/olf and Gαi/o. Disruption of the balance of signaling through these pathways is likely to have pathological consequences. Our laboratory is investigating the role of a GTP-binding protein, Rhes, in regulating DA signaling through these pathways. Behavioral studies in mice indicate that Rhes differentially affects DA-mediated behavior, depending on the signaling cascade involved. We are now testing the mechanism of Rhes actions in DA signaling through protein-protein interaction studies and signaling studies in primary striatal cultures. Acquiring this information will lead to better treatment for disorders such as drug addiction and schizophrenia by demonstrating the range of pathways that can be targeted by drugs in order to alleviate particular dysfunctions.

Research Interests

Keywords:
signal transduction through dopamine receptors, regulation of G protein-coupled receptor signal strength, dopamine receptor-mediated behaviors

Research Interests and Goals:

Our laboratory is focused on signal transduction through dopamine receptors, the regulation of G protein-coupled receptor signaling, and dopamine receptor-mediated behaviors. We are investigating a novel GTP binding protein, Rhes, which is involved in dopamine signaling and has a potential role in dopamine-related disorders such as schizophrenia and drug addiction.

Teaching Activities

2007 – present: Research Assistant Professor of Pharmacologyand Neuroscience, LSU Health Sciences Center

2004-2007: Research Assistant Professor, Department of Psychology, University of New Orleans

Selected Publications

Key Recent Papers:

Quintero, G.C., Spano, D., LaHoste, G.J., Harrison, L.M. The ras homolog rhes affects dopamine D1 and D2 receptor-mediated behavior in mice. NeuroReport 19(16): 1563-1566, 2008.

Harrison, L.M., LaHoste, G.J., Ruskin, D.N. Ontogeny and dopaminergic regulation in brain of ras homolog enriched in striatum. Brain Research 1245: 16-25, 2008.

Nolan E.B., LaHoste G.J., Harrison L.M. and Ruskin D.N. D1/D2 dopamine receptor synergism is intact in connexin 36-deficient mutant mice. Synapse 61(5): 279-87, 2007.

Harrison L.M. and LaHoste G.J. Rhes, the ras homolog enriched in striatum, is decreased under conditions of dopamine receptor supersensitivity. Neuroscience 137(2): 483-92, 2006.

Bunzow J.R., Sonders M.S., Arttamangkul S., Harrison L.M., Zhang G., Quigley D.I., Darland T., Suchland K.L., Pasumamula S., Kennedy J.L., Olson S.B., Magenis R.E., Amara S.G. and Grandy D.K. Amphetamine, 3,4,-methylenedioxy-methamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor. Molecular Pharmacology 60(6): 1181-8, 2001.

Malin D.H., Lake J.R., Moon W.D., Moy D., Montellano A.L., Moy E., Bell M.V., Bryant D., Harrison L.M., and Grandy, D.K. Nociceptin/Orphanin FQ induces a quasi-morphine abstinence syndrome in the rat. Psychopharmacology 151(4): 344-50, 2000.

Harrison, L.M. and Grandy, D.K. Opiate modulating properties of nociceptin/orphanin FQ . Peptides 21(1): 151-172, 2000.

Harrison, L.M., Kastin, A.J. and Zadina, J.E. Opiate tolerance and dependence: Receptors, G-proteins, and antiopiates. Peptides 19(9): 1603-30, 1998.

Harrison, L.M., Kastin, A.J. and Zadina, J.E: Differential effects of endomorphin-1, endomorphin-2, and Tyr-W-MIF-1 on activation of G-proteins in neuroblastoma membranes. Peptides 19(4): 749-53, 1998.

Harrison L.M., Ruskin D.N: The role of dopamine input in maintaining expression of the ras homolog rhes. Brain Research 1245:16-25, 2008.

Nolan E.B., Harrison L.M., LaHoste G.J., Ruskin D.N: Behavioral synergism between D1 and D2 receptors in mice does not depend on gap junctions. Synapse 61:279-287, 2007.

Harrison L.M., LaHoste G.J: Rhes, the Ras homolog enriched in striatum, is reduced under conditions of dopamine supersensitivity. Neuroscience 137(2):483-92, 2006.


Selected Papers:

Harrison L.M., Kastin A.J., and Zadina J.E: Tyr-W-MIF-1 attenuates down-regulation of opiate receptors in SH-SY5Y human neuroblastoma cells. The Journal of Pharmacology and Experimental Therapeutics 284(2): 611-17, 1998.

Banks, W.A., Kastin, A.J., Harrison, L.M. and Zadina, J.E: Perinatal treatment of rats with opiates affects the development of the blood-brain barrier transport system PTS-1. Neurotoxicology and Teratology 18(6): 711-15, 1996.

Zadina, J.E., Harrison, L.M., Ge, L-J, Chang, S.L. and Kastin, A.J: Differential regulation of mu and delta opiate receptors by morphine, selective agonists and antagonists, and differentiating agents in SH-SY5Y human neuroblastoma cells. The Journal of Pharmacology and Experimental Therapeutics 270(3): 1086-1096, 1994.

Harrison, L.M., Zadina, J.E., Banks, W.A. and Kastin, A.J: Effects of neonatal treatment with Tyr-MIF-1, morphiceptin, and morphine on development, tail flick, and blood-brain barrier transport. Developmental Brain Research 75: 207-212, 1993. 

Additional Info

Funding:

“Mentoring Neuroscience in Louisiana”
Role: Promising Young Investigator
Agency: Centers of Biomedical Research Excellence/NIH
(P20 RR016816)
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