Chair and Professor, Pharmacology and Eric L. and Lila D. Nelson Chair in Neuropharmacology
Joint Appointment, Developmental & Cell Biology
Joint Appointment, Pharmaceutical Sciences
|Molecular neurobiology, G protein-coupled receptors, Neuropeptides, Orphan receptors, Novel neurotransmitters, Dopamine receptors, Orphanin FQ/nociceptin, MCH, traditional Chinese medicines|
|URLs||Pharmacology Home Page|
|Dr. Civelli's Lab|
|See below for selected publications or click here for additional publication listings available via PubMed|
1989, Pfizer traveling fellow award, Clinical Research Institute of Montreal
1991, Lecturer in the "Distinguished Speaker Series" of the Department of Pharmacology, University of Toronto
1992, Presidential Lecture, Annual Meeting of the Society for Neuroscience
1992, Robert and Adele Blank Lectureship, New York University Medical Center
2002, Athalie Clarke Research Award, University of California, Irvine
2004, Interviewed by Nature Drug Discovery as one of the 20 world’s leading experts on GPCR research (Nature Drug Discovery 3: 575-626)
2006, ISI Highly Cited Researcher
2010, NARSAD Distinguished Investigator Award
2011 Visiting Professorship for Senior International Scientists, Chinese Academy of Sciences
2011 Guest Professorship, Nantong University, China
2011 Tourette Syndrome Association Research Grant
2015 Chinese Academy of Sciences President’s International Fellowship Initiative for Visiting Scientists
The main focus of our research aims at furthering our understanding of the diversity of brain function by identifying and studying novel molecules which mediate synaptic transmission. Synaptic transmission is the mechanism which underlies the biochemical reactions that make brain functions and relies on the recognition of transmitters by their specific receptors.
Among the receptors that direct brain functions, the most numerous are the G protein-coupled receptors (GPCRs). We have been among the first at the end of the 80”s to clone GPCRs. Several cloned GPCRs do not bind any of the presently known transmitters, these are the "orphan" GPCRs. We expect them to bind thus far undescribed transmitters. This led us to use orphan GPCRs as targets to discover new transmitters. We were the first in 1995 to discover a novel neuropeptide through this approach. Since then, this approach has been used around the world to identify the receptors of a dozen of new transmitters.
The second phase of our studies consists in determining the biological significance of the novel transmitters. We first define the neuronal pathways in which the novel transmitter acts and then determine its effects on physiological responses and behavior. Because transmitters can have a broad spectrum of effects, this part of our approach is combined to two different approaches. The first one is to engineer strains of mice that can point at the roles of the novel transmitter in vivo. The second one is to screen for molecules that can be used in behavioral experiments in controlled conditions. More recently this approach has led us to study traditional medicines as sources of compounds that are validated in their efficacy against particular human disorders.
30 Patents Issued.
Bunzow, J.R., Van Tol, H.H., Grandy, D.K., Albert, P., Salon, J., Christie, M., Machida, C., Neve, K.A. and Civelli, O. (1988) Cloning and expression of a rat D2 dopamine receptor cDNA. Nature, 336:783-787
Zhou, Q.Y., Grandy, D.K., Thambi, L., Kushner, J., Van Tol, H.H.M., Cone, R., Pribnow, D., Salon, J., Bunzow, J.R. and Civelli, O. (1990) Cloning and expression of human and rat D1 dopamine receptors. Nature, 347:76-80.
Van Tol, H.H.M., Bunzow, J.R., Guan, H.C., Sunahara, R.K., Seeman, P., Niznik, H.B. and Civelli, O. (1991) Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature, 350:610-614
Grandy, D.K., Zhang, Y., Bouvier, C., Zhou, Q.Y., Johnson, R.A., Allen, L., Buck, K., Bunzow, J.R., Salon, J. and Civelli, O. (1991) Multiple human D5 dopamine receptor genes: A functional receptor and two pseudogenes. Proceedings of the National Academy of Sciences, USA, 88:9175-9179.
Zhou, Q.Y., Li, C., Olah, M.E., Johnson, R.A., Stiles, G.L. and Civelli, O. (1992) Molecular cloning and characterization of an adenosine receptor: The A3 adenosine receptor. Proceedings of the National Academy of Sciences, USA, 89:7432-7436.
Reinscheid, R.K., Nothacker, H.P., Bourson, A., Ardati, A., Henningsen, R. A., Bunzow, J.R., Grandy, D.K., Langen, H., Monsma, F.J. and Civelli, O. (1995) Orphanin FQ: A neuropeptide that activates an opioid-like G protein-coupled receptor. Science, 270:792-794.
Jenck, F., Moreau, J.L., Martin, J.R., Kilpatrick, G.J., Reinscheid, R.K., Monsma, F.J., Nothacker, H.P. and Civelli, O (1997) Orphanin FQ acts as an anxiolytic to attenuate behavioral responses to stress. Proceedings of the National Academy of Sciences, USA, 94:14854-14858
Saito, Y., Nothacker, H.P., Wang, Z., Lin, S.H.S., Leslie, F. and Civelli, O. (1999) Molecular characterization of the melanin-concentrating hormone receptor. Nature, 400:265-269.
Nothacker, H.P., Wang, Z., McNeill, A.M., Saito, Y., Merten, S., O’Dowd, B., Duckles, S.P. and Civelli, O. (1999) Identification of the natural ligand of an orphan G protein-coupled receptor involved in the regulation of vasoconstriction. Nature Cell Biology, 1:383-385.
Xu, Y.L., Reinscheid, R.K., Huitron-Resendiz, S., Clark, S.D., Wang, Z, Lin, S.H., Brucher, F.A., Zeng, J., Ly, N.K, Henriksen, S.J., de Lecea, L., and Civelli, O. (2004). Neuropeptide S: a novel neuropeptide promoting arousal and anxiolytic-like effects Neuron 43:487-497.
Nagasaki, H., Chung, S., Dooley, C.T., Wang, Z., Li, C., Saito, Y., Clark, S.D., Houghten, R.A. and Civelli, O. (2009) The pharmacological properties of a novel MCH1 receptor antagonist isolated from combinatorial libraries. European Journal of Pharmacology 602:194-202
Chung S., Hopf F.W., Nagasaki H., Li CY., Belluzzi J.D., Bonci A. and Civelli O. (2009) The melanin-concentrating hormone system modulates cocaine reward. Proceedings National Academy of Sciences, USA 106(16):6772-6777.
Chung, S., Verheij, M.M., Hesseling, P., van Vugt, R.W., Buell, M., Belluzzi, J.D., Geyer, M.A., Martens, G.J. and Civelli O. (2011) The Melanin-Concentrating Hormone (MCH) System Modulates Behaviors Associated with Psychiatric Disorders PLoS One. 2011;6(7):e19286. Epub 2011 Jul 19.
Civelli O (2013) Orphan GPCRs and Neuromodulation. Neuron. Oct 4;76(1):12-21.
Civelli O, Reinscheid RK, Zhang Y, Wang Z, Fredriksson R, Schiöth HB (2013) G Protein-Coupled Receptor Deorphanizations. Annual Review of Pharmacology and Toxicology 53:127-146
Zhang Y, Wang C, Wang L, Parks GS, Zhang X, Guo Z, Ke Y, Li KW, Kim MK, Vo B, Borrelli E, Ge G, Yang L, Wang Z, Garcia-Fuster MJ, Luo ZD, Liang X, Civelli O (2014) A Novel Analgesic Isolated from a Traditional Chinese Medicine. Curr Biol. 2014 24 1-7
|Wang L, Alachkar A, Sanathara N, Belluzzi JD, Wang Z, Civelli O (2015).A Methionine-Induced Animal Model of Schizophrenia: Face and Predictive Validity. Int J Neuropsychopharmacol. 18(12).|
|Grant||National Institute on Drug Abuse (NIDA) R01 DA024746, 02/01/10-01/31/14, $1,033,372 direct costs, A novel neuropeptide system involved in drug abuse (Role: P.I.).|
European College of Neuropsychopharmacology
American Society for Pharmacological and Experimental Therapeutics
American Association of the Advancement of Science
American Society for Neuroscience
European Neuroscience Association
American College of Neuropsychopharmacology
Chair, Department of Pharmacology
School of Medicine, UC Irvine 2011—pres
F. Hoffmann-La Roche, AG 1992—1996
Interdepartmental Neuroscience Program
Cellular and Molecular Biosciences
Medicinal Chemistry and Pharmacology
|Link to this profile||http://www.faculty.uci.edu/profile.cfm?faculty_id=3277|