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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.
Photo of David R. Sibley, Ph.D., Senior Investigator

Staff:



Research Interests:
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. (InPress) Discovery, optimization, and characterization of novel D2 dopamine receptor selective antagonists, Journal of Medicinal Chemistry. 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. (InPress) Discovery and characterization of a G protein-biased agonist that inhibits β-arrestin recruitment to the D2 dopamine receptor, Molecular Pharmacology.

  • Chun, L.S., Free, R.B., Doyle, T.B., Huang, X.-P., Rankin, M.L., and Sibley, D.R. (2013) D1-D2 dopamine receptor synergy promotes calcium signaling via multiple mechanisms, Molecular Pharmacology 84:, 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., (2013) Modification cocaine self-administration by buspirone (BusparŪ): potential involvment of D3 and D4 dopamine receptors, International Journal of Neuropsychopharmacology 16: , 445-458. Full Text/Abstract

  • Newman, A.H., Blaylock, B.L., Nader, M.A., Bergman, J., Sibley, D.R., Skolnick, P., (2012) Medication Discovery for Addiction: Translating the Dopamine D3 Receptor Hypothesis, Biochemical Pharmacology, 84: , 882-890, . 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., (2011) 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 54: , 3581-3594, . Full Text/Abstract

  • Skinberb, M., Sibley, D.R., Javitch, J.A., and Abi-Dargham, A., (2011) Imaging the High Affinity State of the Dopamine D2 Receptor: fact or fiction,, Biochemical Pharmacology, 83: , 193-198,. Full Text/Abstract

All Selected Publications


Contact Information:

Dr. David R. Sibley
Molecular Neuropharmacology Section, NINDS
5625 Fishers Lane, Room 4S-04
MSC-9405
Bethesda, MD 20892-9405

Telephone: (301) 496-9316 (office), (301) 496-6329 (laboratory), (301) 480-3726 (fax)
Email: sibleyd@ninds.nih.gov

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