Molecular Neuropharmacology Section - Division of Intramural Research
David R. Sibley, Ph.D., Senior Investigator
Dr. Sibley received his B.S. degree in Biology from San Diego State University and his Ph.D. in Physiology/Pharmacology from the University of California, San Diego where he worked with Ian Creese studying the ligand binding properties of dopamine receptors. He subsequently carried out postdoctoral work with Robert Lefkowitz at Duke University where he characterized adrenergic receptor regulatory mechanisms. Dr. Sibley moved to the NINDS in 1987 and was appointed Chief of the Molecular Neuropharmacology Section in 1992. His laboratory is currently investigating the molecular, cellular and biochemical properties of dopamine receptors and their role in neuronal signaling.
, B.S., Office Manager
, B.S., Graduate Student
, Ph.D., Postdoctoral Fellow
R. Benjamin Free
, Ph.D., Staff Scientist
Julia A. Meade
, B.A., Postbaccalaureate IRTA
, M.S., Laboratory Manager
, Ph.D., Postdoctoral Fellow
, Ph.D., Special Volunteer
The long-term goal of the Molecular Neuropharmacology Section is the characterization of neurotransmitter receptor-mediated information transduction, and its regulation, across neuronal membranes. The primary model systems under investigation are those neurotransmitter receptors that are linked to their signal transduction pathways via guanine nucleotide binding regulatory (G) proteins with specific emphasis on dopamine receptor subtypes. Specific G proteins have been shown to link these receptors to the activation and inhibition of various nucleotide cyclases, phospholipases, and several ion channels. In order to characterize these receptors at the biochemical and molecular levels and study their regulation, there are several ongoing interrelated lines of research. Such projects include investigating receptor structure/function/pharmacology relationships, receptor-effector coupling mechanisms, G protein interactions, and molecular mechanisms of receptor desensitization and intracellular trafficking. We are also interested in using high throughput screening approaches to develop novel ligands for modulating dopamine receptor expression and signaling. These ligands may prove useful in the development of novel pharmacological therapies for treating numerous neurological and psychiatric disorders associated with aberrant dopaminergic signaling.
Selected Recent Publications
Xiao, J., Free, R.B., Barnaeva, E., Conroy, J.L., Doyle, T.B., Miller, B., Bryant-Genevier, M., Taylor, M.K., Hu. X., Dulcey, A. E., Southall, N., Ferrer, M., Titus, S., Zheng, Z., Sibley, D.R., and Marugan, J.J.
Discovery, optimization, and characterization of novel D2 dopamine receptor selective antagonists, Journal of Medicinal Chemistry, 2014 Full Text/Abstract
Free, R.B., Chun, L.S., Moritz, A.E., Miller, B., Doyle, T.B., Conroy, J.L., Padron, Meade, J.A., Xiao, J., Hu, X., Dulcey, A.E., Han, Y., Duan, L., Titus, Bryant-Genevier, M., Barnaeva, E., Ferrer, M., Javitch, J.J., Beuming, T., Shi, L., Southall, N., Marugan, J.J., and Sibley, D.R.
Discovery and characterization of a G protein-biased agonist that inhibits β-arrestin recruitment to the D2 dopamine receptor, Molecular Pharmacology, 2014
Chun, L.S., Free, R.B., Doyle, T.B., Huang, X.-P., Rankin, M.L., and Sibley, D.R.
D1-D2 dopamine receptor synergy promotes calcium signaling via multiple mechanisms, Molecular Pharmacology, 2013, vol. 84:, pp. 190-200. Full Text/Abstract
Bergman, J., Roof, R.A., Furman, C.A., Conroy, J.L., Mello, N.K., Sibley, D.R., and Skolnick, P.,
Modification cocaine self-administration by buspirone (Buspar®): potential involvment of D3 and D4 dopamine receptors, International Journal of Neuropsychopharmacology, 2013, vol. 16:, pp. 445-458. Full Text/Abstract
Newman, A.H., Blaylock, B.L., Nader, M.A., Bergman, J., Sibley, D.R., Skolnick, P.,
Medication Discovery for Addiction: Translating the Dopamine D3 Receptor Hypothesis, Biochemical Pharmacology,, 2012, vol. 84:, pp. 882-890,. Full Text/Abstract
Skinberb, M., Sibley, D.R., Javitch, J.A., and Abi-Dargham, A.,
Imaging the High Affinity State of the Dopamine D2 Receptor: fact or fiction,, Biochemical Pharmacology,, 2011, vol. 83:, pp. 193-198,. Full Text/Abstract
Banala, A.K., Levy, B.A., Khatri, S.S., Furman, C.A., Roof, R.A., Mishra, Y., Griffin, S.A., Sibley, D.R., Luedtke, R.R., Hauk-Newman, A.,
N-(3-Fluoro-4-(4-(2-methoxy or 2,3-dichlorophenyl) piperazine-1-yl)-butyl)-aryl carboxamides as Selective Dopamine D3 Receptor Ligands: Critical Role of the Carboxamide Linker for D3 Receptor Selectivity, Journal of Medicinal Chemistry, 2011, vol. 54:, pp. 3581-3594,. Full Text/Abstract
Rankin, M.L., and Sibley, D.R.
Consitutive phosphorylation by protein kinase C regulates D1 dopamine receptor signaling, Journal of Neurochemistry, 2010, vol. 115, pp. 1655-1667. Full Text/Abstract
Selected Earlier Publications