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| David R. Sibley, Ph.D., Senior Investigator |
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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.
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Staff:
- Lani Chun, B.S., Graduate Student, (301) 451-9163 Lani.Chun@nih.gov
- Jennie Conroy, Ph.D., Postdoctoral Fellow, (301) 451-9164 conroyjl@mail.nih.gov
- R. Benjamin Free, Ph.D., Staff Scientist, (301) 443-4785 freeb@ninds.nih.gov
- Deborah Holland, Office Manager, (301) 435-3883 deborahh@ninds.nih.gov
- Julia A. Meade, B.A., Postbaccalaureate IRTA, (301) 594-5277 julie.meade@nih.gov
- Amy Moritz, Ph.D., Postdoctoral Fellow, (301) 443-4790 moritzae@mail.nih.gov
- Adrian Padron, B.S., Laboratory Manager, (301) 496-5618 padronan@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 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.
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Selected Recent Publications:
Chun, L.S., Free, R.B., Doyle, T.B., Huang, X.-P., Rankin, M.L., and Sibley, D.R. (InPress) D1-D2 dopamine receptor synergy promotes calcium signaling via multiple mechanisms, Molecular Pharmacology.
Full Text/Abstract
Rex, E., Rankin, M.L., Yang, Y., Lu, Q., Gerfen, C.R., and Sibley, D.R. (2010) Identification of RanBP9/10 as interacting partners for protein kinase Cs γ/δ and the D1 dopamine receptor: regulation of PKC-mediated receptor phosphorylation, Molecular Pharmacology 78, 69-80.
Full Text/Abstract
Rankin, M.L., and Sibley, D.R. (2010) Consitutive phosphorylation by protein kinase C regulates D1 dopamine receptor signaling, Journal of Neurochemistry 115, 1655-1667.
Full Text/Abstract
Namkung, Y., Dipace, C., Javitch, J.A., and Sibley, D.R. (2009) G protein-coupled receptor kinase-mediated phosphorylation mediates post-endocytic trafficking of the D2 dopamine receptor, Journal of Biological Chemistry 284, 15038-15051.
Full Text/Abstract
Namkung, Y., Dipace, C., Urizar, U., Javitch, J.A., and Sibley, D.R. (2009) G protein-coupled receptor kinase-2 constitutively regulates D2 receptor expression and signaling independent of receptor phosphorylation, Journal of Biological Chemistry 284, 34103-34115.
Full Text/Abstract
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.
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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
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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