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Faculty Detail    
Name ROBIN A J LESTER
 
Campus Address SHEL 1006 Zip 2182
Phone 205-934-4483
E-mail nicotine@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Neurobiology  Neurobiology Professor
Secondary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Professor
Secondary  Pharmacology/Toxicology   Pharmacology/Toxicology Chair's Office Associate Professor
Center  Civitan International Research Center  Civitan International Research Center Professor
Center  General Clinical Research Center  Comprehensive Neuroscience Center Professor

Graduate Biomedical Sciences Affiliations
Cellular and Molecular Biology Program 
Hughes Med-Grad Fellowship Program 
Integrative Biomedical Sciences 
Medical Scientist Training Program 
Neuroscience 
Neuroscience Graduate Program 
Neurosciences 

Biographical Sketch 
Robin A.J. Lester received his Ph.D. in Pharmacology from the University of Bristol, UK in 1988. Following a Research Assistant Professor position at Baylor College of Medicine, he joined UAB in 1995. He is presently an Associate Professor of Neurobiology.

Research/Clinical Interest
Title
Molecular & Cellular Mechanisms of Nicotine Addiction
Description
The critical role of CNS nicotinic acetylcholine receptors (nAChRs) in tobacco addiction has focused our attentions on understanding the overall function of these receptors in the brain both under physiological and diseased conditions. nAChRs are ligand-gated ion channels composed of five individual protein subunits that cause neuronal excitation when bound and activated by synaptically released neurotransmitter, acetylcholine, or exogenous drugs like nicotine. Molecular biological studies have characterized at least twelve receptor subunits that can be assembled together in numerous combinations giving rise to a wide variety of nAChRs with distinct functional roles. It is because of this diversity that nAChRs have been implicated in a range of CNS behaviors from pain sensation to learning and memory, and multiple pathological states such as epilepsy and schizophrenia. High-resolution electrophysiological (patch-clamp) techniques combined with intracellular calcium measurements provide the most powerful way of examining these receptors. The physiological and pharmacological properties of single and multiple nAChR channels in isolated membrane patches and whole cells can be fully resolved using these methods. The roles of nAChRs at both pre and postsynaptic zones of central synapses can be studied by recording from visually identified neurons in brain slice preparations. These approaches are complemented by molecular biological approaches that allow the expression and characterization of known cloned nAChRs and the determination of nAChR RNAs from CNS neurons (by single cell RT-PCR). Thus, a full array of methods are available to address the following types of questions. How do nAChRs contribute to synaptic transmission and plasticity? How are nAChRs regulated by intracellular calcium, phosphorylation and the cytoskeleton? How does chronic nicotine affect the long-term functioning of the various nAChRs and untilmately lead to drug craving and relapse?

Selected Publications 
Publication PUBMEDID
Fenster, C.P., Rains, M.F., Noerager, B., Quick, M.W. and Lester, R.A.J. Influence of subunit composition on desensitization of nicotinic receptors at low concentrations of nicotine. J. Neurosci. 17: 5747-5759, 1997.  9221773 
Quick, M.W. and Lester, R.A.J. Desensitization of neuronal nicotinic receptors J. Neurobiol. 53:457-478.2002.  8943251 
Guo, X. and Lester, R.A.J. Ca2+ flux and signaling implications by nicotinic acetylcholine receptors in rat medial habenula. J. Neurophysiol. 97:83-92, 2007a.   17050826 
Guo, X.and Lester, R.A.J. Regulation of nicotinic acetylcholine receptor desensitization by Ca2+. J. Neurophysiol. 97:93-101, 2007b.  17050825 
Cho, C.-H., Song, W., Leitzell, K., Teo, E., Meleth, A.D., Quick, M.W. and Lester, R.A.J. Rapid upregulation of alpha7 nicotinic acetylcholine receptors by tyrosine dephosphorylation.
J. Neurosci. 25:3712-3723, 2005. 
15814802  
Lester, R.A.J. Activation and desensitization of heteromeric neuronal nicotinic receptors: implications for non-synaptic transmission.
Bioorg. Med. Chem. Lett. 14:1897-1900, 2004. 
15050622 
Parker, J.C., Sarkar, D., Quick, M.W. and Lester, R.A.J. Interactions of atropine with heterologously expressed and native alpha3 subunit-containing nicotinic acetylcholine receptors. Br. J. Pharmacol. 138:801-810, 2003.  12642381 
Hicks, J.H., Dani, J.A. and Lester, R.A.J. Regulation of the sensitivity of acetylcholine receptors to nicotine in rat medial habenula neurons. J. Physiol. 529: 579-597, 2000.  11118491 
Sheffield, E.B., Quick, M.W. and Lester, R.A.J. Nicotinic acetylcholine receptor subunit mRNA expression and channel function in medial habenula neurons. Neuropharmacol. 39:2591-2603, 2000.  11044729 
Fenster, C.P., Whitworth, T., Quick, M.W and Lester, R.A.J. Upregulation of surface alpha4beta2 nicotinic receptors is initiated by receptor desensitization following chronic exposure to nicotine. J. Neurosci., 19:4804-4814, 1999a.  10366615 
Fenster, C.P., Beckman, M.L., Parker, J.C., Sheffield, E.B., Whitworth, T.L., Quick, M.W. and Lester, R.A.J. Regulation of alpha4beta2 nicotinic receptor desensitization by calcium and protein kinase C. Mol. Pharmacol., 55:432-443, 1999b.  10051526