Thomas Jefferson University - Michael E. O'Leary
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Michael E. O'Leary
Pathology, Anatomy and Cell Biology
Thomas Jefferson University
Jefferson Medical College
Department of Pathology
Anatomy & Cell Biology
Associate Professor
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Mailing Address
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1020 Locust Street, JAH 265
Philadelphia, Pennsylvania 19107
United States
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Qualifications
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Ph.D., College of Medicine, Physiology and Biophysics, 1987
M.S., University of Connecticut, Physiology, 1982
B.S., University of Connecticut, Biology, 1978
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Expertise and Research Interests
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Sensory nerve fibers originate in the dorsal root ganglion and produce long branches that terminate in peripheral tissues. The termini of these sensory neurons elaborate specialized membrane bound proteins that convert mechanical, thermal, and chemical stimuli into electrical signals that are transmitted along the sensory nerve fibers back to the spinal cord. Included in these sensory nerve fibers are subsets of unmyelinated fibers that predominately respond to painful stimuli. These nociceptive nerve fibers are the initial link in the pain-sensing pathway. The research in my laboratory utilizes a combination of electrophysiology and molecular biology to investigate the mechanisms of sensory neuron transduction and the propagation of electrical signals along nociceptive nerve fibers. To do this we developed novel methodologies that permit electrical recording and genetic screening of individual sensory neurons. Quantitative analysis of the mRNA transcripts expressed in single nociceptors enables us to correlate the electrical properties with the specific proteins expressed in these neurons. Using this approach we have identified voltage-gated ion channels that are uniquely expressed in nociceptors. The long-term goal of our studies is to identify the ligand- and voltage-gated ion channels expressed in nociceptors. These findings will enhance our understanding of nociceptor function and guide the development of novel strategies for treating acute and chronic pain.
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Keywords
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Sensory neuron, Sodium channel, potassium channel, RT-PCR, Patch clamp, Voltage Clamp
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Publications
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- O'Leary M.E. and J.C. Hancox, Role of voltage-gated sodium, potassium and calcium channels in cocaine-associated cardiac arrhythmia. British Journal of Clinical Pharmacology (In Press).
- Zhao, J., Zaine, R., Chatelier, A., O'Leary, M., Chahine M., (2007) Lidocaine promotes the trafficking and functional expression of Nav1.8 sodium channels in mammalian cells. Journal of Neurophysiology, 98:467-477.
- Winkelman, LB., C.L. Beck, D.L. Ypey, and M.E. O'Leary, (2005) Inhibition of the A-type K channels of dorsal root ganglion neurons by the long duration anesthetic butamben. Journal of Pharmacology and Experimental Therapeutics, 314:1177-1186.
- Ramos, E. and M.E. O'Leary, (2004) State-dependent trapping of flecainide in the cardiac sodium channel. Journal of Physiology, 560:37-49.
- O'Leary, M.E., DiGregorio, M., and M. Chahine, (2003) Closing and inactivation of cardiac sodium channels stabilize cocaethylene binding by different mechanisms. Molecular Pharmacology, 64:1575-1585.
- Beekwilder, J.P., O'Leary, M.E., van den Broek, L.P., Van Kempen, G.Th.H., Ypey, D.L., and R.J. Van den Berg, (2003) Kv1.1 channels of dorsal root ganglion neurons are inhibited by n-butyl-p-aminobenzoate, a promising anesthetic for the treatment of chronic pain. Journal of Pharmacology and Experimental Therapeutics, 304:531-538.
- O'Leary M.E., and M. Chahine, (2002) Cocaine binds to a common site on open and inactivated human heart (Nav1.5) sodium channels. Journal of Physiology, 541:701-716.
- O'Leary, M.E, (2002) Inhibition of HERG potassium channels by cocaethylene; a metabolite of cocaine and ethanol. Cardiovascular Research, 53:59-67.
- Vijayaragavan, K., O'Leary, M.E., and M. Chahine, (2001) Modulation of peripheral nerve sodium channels Nav1.7 and Nav1.8 by the b1 subunit. Journal of Neurophysiology, 21:7909-7918.
- O'Leary, M.E., (2001) Inhibition of human ether-a-go-go potassium channels by cocaine. Molecular Pharmacology, 59:269-277.
- O'Leary M.E., (1998) Characterization of the isoform-specific differences in the gating of neuronal and muscle sodium channels. Canadian Journal of Physiology and Pharmacology, 76:1041-1050.
- O'Leary M.E., Chen, L.Q., Kallen, R.G., and R. Horn, (1995) A molecular link between activation and inactivation of sodium channels. Journal General Physiology, 106:641-658.
- O'Leary M.E., Kallen, R.G., and R. Horn, (1994) Evidence for a direct interaction between internal tetra-alkylammonium cations and the inactivation gate of cardiac sodium channels. Journal of General Physiology, 104:523-539.
- O'Leary M.E., and R. Horn, (1994) Internal block of human heart sodium channels by symmetrical tetra-alkylammoniums. Journal of General Physiology, 104:507-522.
- O'Leary M.E., Filatov, G.N., and M.W. White, (1994) Characterization of d-tubocurarine binding site of Torpedo acetylcholine receptor. American Journal of Physiology, 266:C648-C653.
- O'Leary, M.E., and M.W. White, (1992) Mutational analysis of ligand induced activation of the Torpedo acetylcholine receptor. Journal of Biological Chemistry, 267:8360-8365.
- O'Leary M.E., and B.K. Krueger, (1989) Batrachotoxin and a-scorpion toxin stabilize the open state of single voltage-gated sodium channels. Molecular Pharmacology, 36:789-795.
- Suszkiw J.B., O'Leary, M.E., Murawsky, M.M., and T. Wang, (1986) Presynaptic calcium channels in rat cortical synaptosomes: Fast-kinetics of phasic calcium influx, channel inactivation, and relationship to nitrendipine receptors. Journal of Neuroscience, 6:1349-1357.
- Suszkiw, J.B.,and M.E. O'Leary, (1983) Temporal characteristics of K-evoked ACh release and inactivation of Ca2+ influx in rat brain synaptosomes. Journal of Neurochemistry 41:868-873.
- O'Leary, M.E., and J.B. Suszkiw, (1983) Effect of colchicine on Ca2+ and choline uptake and acetylcholine release in rat brain synaptosomes. Journal of Neurochemistry 40:1192-1195.
- Suszkiw, J.B., and M.E. O'Leary, (1982) Differential labeling of depot and active acetylcholine pools in non-depolarized and potassium-depolarized rat brain synaptosomes. Journal of Neurochemistry 38:1668-1675.
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Individual Expertise profile of
Michael E. O'Leary, Copyright © Michael E. O'Leary.
Last Updated
by Admin
: Wednesday, October 14, 2009 10:35:42 AM
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