Val J. Watts

Val J. Watts Profile Picture

Professor of Medicinal Chemistry and Molecular Pharmacology
Ph.D. - 1994 - University of North Carolina at Chapel Hill

Contact Info:

Training Group(s):
Integrative Neuroscience
Membrane Biology

Active Mentor - currently hosting PULSe students for laboratory rotations and recruiting PULSe students into the laboratory; serves on preliminary exam committees

Current Research Interests:

My research program studies the signaling pathways of G protein-coupled receptors with an emphasis on dopamine receptor systems. Dopamine receptors are of particular interest because they have been implicated in a variety of neurological disorders including schizophrenia, depression, Parkinson's disease and drug abuse. We are currently examining the effects of dopamine receptor agonist activation on second messenger systems and the effects of short and long-term agonist exposure on receptors, G proteins, and adenylate cyclases. For example, acute activation of the D2 dopamine receptor inhibits adenylate cyclase activity, however persistent activation of the D2 dopamine receptor leads to heterologous sensitization of adenylate cyclase. Heterologous sensitization is characterized by an enhanced response to drug-stimulated adenylate cyclase activity following persistent/chronic D2 receptor activation. Understanding the mechanisms involved in heterologous sensitization is complicated by the fact that there several families of G proteins that may be involved with the regulation of at least 9 molecular isoforms of the enzyme adenylate cyclase. Furthermore, each isoform of adenylate cyclase is differentially regulated, suggesting that there may be isoform specificity for heterologous sensitization. The overall goal of these studies is to identify cellular and molecular mechanisms for receptor-mediated changes at the receptor, G protein, and effector levels.

Selected Publications:

Cueva, J.P., Gallardo-Godoy, A., Juncosa, J.I., Vidi, P.A., Lill, M.A., Watts, V.J., and Nichols, D.E.., Probing the steric space at the floor of the D1 dopamine receptor orthosteric binding domain: 7a-, 7ß-, 8a-, and 8ß-methyl substituted dihydrexidine analogues. J. Med. Chem. (in press 2011).

Meyer, J.M., Ejendal, K.F., Watts, V.J., and Hill, C.A Molecular and pharmacological characterization of two D(1)-like dopamine receptors in the Lyme disease vector, Ixodes scapularis. Insect Biochem. Mol. Biol. 41:6763-6770, 2011.

Vidi, P.A., Ejendal, K.F.K., Przybyla, J.A., and Watts, V.J., Fluorescent protein complementation assays: new tools to study G protein-coupled receptor oligomerization and GPCR-mediated signaling. Mol. Cell. Endocrinol., 331:185-193, 2011.

Ejendal, K.F.K., Przybyla, J.A. and Watts, V.J., Adenylyl cyclase isoform-specific signaling of GPCRs. G Protein-Coupled Receptors: Structure, Signaling, and Physiology; Siehler, S. and Milligan, G., Editors; Cambridge University Chapter 10, 189-217, 2010.

Przybyla, J.A. and Watts, V.J., Ligand-induced regulation and localization of cannabinoid CB1 and dopamine D2 receptor heterodimers. J. Pharmacol. Exp. Therap., 332:710-719, 2010.

Vidi, P.A., Przybyla, J.A., Hu, C.D., and Watts, V.J. Visualization of G protein-coupled receptor (GPCR) interactions in living cells using bimolecular fluorescence complementation (BiFC) Curr. Protoc. Neurosci. Chapter 5, 5.29, 2010.

Przybyla, J.A., Chemel, B.R., Hsu, K.J., Riese, D.J., McCorvy, J. D., Chester, J.A., Nichols, D.E., and Watts, V.J. Comparison of the enantiomers of (±)-doxanthrine, a high efficacy full dopamine D1 receptor agonist, and a reversal of enantioselectivity at D1 versus alpha2C adrenergic receptors. Eur. J. Neuropsychopharmacol. 19:138-146, 2009.

Vidi, P.A., Chemel, B.R., Hu, C.-D., and Watts, V.J. Ligand-dependant oligomerization of dopamine D2 and adenosine A2A receptors in living neuronal cells. Mol. Pharmacol. 74:544-551, 2008.

Chester, J.A. and Watts, V.J. Adenylyl Cyclase 5: A New Clue in the Search for the "Fountain of Youth"? Sci STKE. 2007: pe64, 2007.

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