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Molecular Neuropharmacology Section
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.
Staff:
- David Cabrera, M.Sc, Laboratory Administrator, 301-496-5618 cabrerad@ninds.nih.gov
- R. Benjamin Free, Ph.D., Postdoctoral Fellow, 301-443-4785 freeb@ninds.nih.gov
- Lisa Hazelwood, Ph.D., Postdoctoral Fellow, 301-496-5919 hazelwol@ninds.nih.gov
- Ms. Deborah Holland, Office Manager, 301-435-3883 deborahh@ninds.nih.gov
- Yoon Namkung, Ph.D., Postdoctoral Fellow, 301-451-9163 namkungy@ninds.nih.gov
- Michele Rankin, Ph.D., Postdoctoral Fellow, 301-594-5277 rankinm@ninds.nih.gov
- Elizabeth Rex, Ph.D., Postdoctoral Fellow, 301-451-9164 elizabeth.rex@mail.nih.gov
- Rebecca A. Roof , Ph.D., Postdoctoral Fellow, 301-496-6329 roofra@ninds.nih.gov
- Mette Skinbjerb, M.S., Predoctoral Fellow, 301-496-6329 Mette@MAIL.NIH.GOV
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 which 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. These include investigating receptor structure/function/pharmacology relationships, receptor-effector coupling mechanisms, G protein interactions, and molecular mechanisms of receptor desensitization. A long standing interest is characterizing the interactions of novel antipsychotic drugs with dopamine receptor subtypes. Additional projects involve the molecular cloning and expression of genes encoding proteins which interact with dopamine receptors, site-directed mutagenesis and receptor chimera studies, analysis and characterization of gene structure, and regulation of receptor expression in both normal and pathophysiological states. Transgenic and receptor "knock-out/in" animal projects are also in progress.
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Selected Publications:
- Kim, O.J., Ariano, M.A., Namkung, Y., Marinec, P., Kim, E., Han, J., and David R. Sibley (2008) D2 dopamine receptor expression and trafficking is regulated through direct interactions with ZIP, Journal of Neurochemistry 106, 83-95. Full Text/Abstract
- Rex, E.B., Rankin, M.L., Ariano, M.A., and Sibley, D.R. (2008) Ethanol Regulation of D1 Dopamine Receptor Signaling is Mediated by Protein Kinase C in an Isozyme-Specific Fashion, Neuropsychopharmacology 32, 2900-2911. Full Text/Abstract
- Hazelwood, L.A., Free, B.F., Cabrera, D.M., Skinbjerb, M., and Sibley, D.R. (2008) Reciprocal modulation of function between the D1 and D2 dopamine receptors and the Na+, K+-ATPase, Journal of Biological Chemistry 283, 36441-36453. Full Text/Abstract
- Free, R.B., Hazelwood, L.A., Namkung, Y., Cabrera, D.M., Spalding, H.N., Rankin, M.L., and Sibley, D.R., (2007) D1 and D2 Dopamine Receptor Expression is Regulated by Direct Interaction with the Chaperone Protein Calnexin, Journal of Biological Chemistry 282, 2185-21300. Full Text/Abstract
- Rankin, M.L., Marinec, P.S., Cabrera, D.M., and Sibley, D.R. (2006) The D1 Dopamine Receptor is Constitutively Phosphorylated by G Protein Coupled Receptor Kinase 4: evidence for a novel mechanism of regulation, Molecular Pharmacology 69, 759-769 (see "Perspectives" article in same issue). Full Text/Abstract
- Kim, O.-J., Gardner, B.R., Williams, D.B., Marinec, P.S., Cabrera, D.M., Peters, J.D., Mak, C.C., Kim, K.-M. and Sibley, D.R. (2004) The Role of Phosphorylation in D1 Dopamine Receptor Desensitization: Evidence for a Novel Mechanism of Arrestin Association, Journal of Biological Chemistry 279, 7999-8010. Full Text/Abstract
- Namkung, Y. and Sibley, D.R. (2004) Protein Kinase C Mediates Phosphorylation, Desensitization and Trafficking of the D2 Dopamine Receptor, Journal of Biological Chemistry 279, 49533-49541. 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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