Val J. Watts

Associate Dean for Research, College of Pharmacy, Associate Head, Department of Medicinal Chemistry and Molecular Pharmacology, Professor of Medicinal Chemistry and Molecular Pharmacology
Phone:
765-496-3872
Fax:
765-494-1414
Specialization: Molecular Pharmacology

Education

B.S. - Pharmacy 1990 Ohio Northern University
Ph.D. - Pharmacology 1994 University of North Carolina (Dr. Richard B. Mailman)
Postdoc. - Molecular Pharmacology 1995-1998 Oregon Health Sciences University (Dr. Kim Neve)

Research

The research in the Watts laboratory is designed to use a multi-disciplinary approach, combining molecular biology, biochemistry, and pharmacology to study the signaling mechanisms of G protein-coupled receptors (GPCRs) and regulation of endogenous and recombinant adenylyl cyclases.  The fact that GPCRs are the target of more the 50% of today’s clinically used drugs emphasizes further the importance of these studies.  Much of the work in his lab has focused on members of the dopamine, cannabinoid, serotonin, and adenosine receptor families.  Studies have examined the pharmacology of these receptors including the characterization of novel ligands that activate these receptors as well as investigating their ability to modulate the activity of their primary effector, the enzyme adenylyl cyclase (AC).  A second area of focus has included examining the effects of persistent Gai/o-coupled receptor activation in vitro in order to understand and identify molecular changes following chronic drug exposure that may occur in vivo.  Much of this work has focused on elucidating the mechanisms for D2 dopamine receptor-induced heterologous sensitization of adenylyl cyclase.  Other exciting studies have also provided evidence that prolonged receptor activation can modulate receptor oligomerization. These investigations used bimolecular fluorescence complementation (BiFC) as well as FLIM-FRET as tools to study directly receptor homodimer and heterodimer formation in living cells.  BiFC and multicolor BiFC represent novel approaches that can be used to “visualize” and localize protein-protein interactions in living cells and are based on the complementation between fragments of fluorescent proteins that are fused to two interacting proteins.  These fluorescent approaches and others are currently being used to study drug-modulated GPCR-b arrestin, GPCR-AC, and AC-AC interactions in novel cellular models as well as in BiFC screening endeavors. More recent efforts have been focused on the development and execution of screening endeavors relevant to drug discovery and AC signaling. We have developed a number of new HTS assays for human and invertebrate GPCRs as well as individual AC isoforms that include using siRNA and small molecule libraries.  

 

Click here for PubMed Publications or see below:

Representative Publications

Brust, T.F., Alongkronusmee, D. Soto-Velasquez, M., Baldwin, T.A., Ye, Z, Dai, M. Dessauer, C.W., van Rijn, R.M., and Watts, V.J., Identification of a selective small molecule inhibitor of type 1 adenylyl cyclase activity with analgesic properties. Sci. Signal.10: eaah5381, 2017 PMID: (in press)

Rana, N., Conley, J.M., Soto-Velasquez, M., Leon, F., Cutler, S.J., Watts, V.J. and Lill, M.A., Molecular modeling evaluation of the enantiomers of a novel adenylyl cyclase 2 inhibitor. J. Chem. Inf. Model. 2017 Jan 9. doi: 10.1021/acs.jcim.6b00454. [Epub ahead of print] PMID:  28068084

Dessauer, C.W. Ostrom, R.S., Watts, V.J., Conti, M., Steegborn, C., Dove, S., and Seifert, R.  International Union of Basic and Clinical Pharmacology: Mammalian adenylyl cyclases as possible drug targets. Pharmacol. Rev. 69:1-27 (in press). DOI: 19.1124/pr.116.013078

BÅ�ehová, P., Šmídková, M., Skácel, J., DraÄ�ínský, M. Mertlíková-Kaiserová, H., Soto Velasquez, M. ,Watts, V.J., and Janeba, Z. B Design and synthesis of fluorescent acyclic nucleoside phosphonates as potent inhibitors of bacterial adenylate cyclases. Chem Med Chem 11: 2534-2546, 2016 PMID: 27775243

Hill, C.A., Doyle, T., Nuss, A.B., Ejendal, F.K.F, Meyer, J.M., and Watts, V.J. Comparative pharmacological characterization of D1-like dopamine receptors from Anopheles gambiae, Aedes aegypti and Culex quinquefasciatus suggests pleiotropic signaling in mosquito vector lineages. Parasit. Vectors 9: 192, 2016 PMID: 27048546 

Brust, T.F., Conley, J.M., and Watts, V.J. Gai/o-coupled receptor-mediated sensitization of adenylyl cyclase: 40 years later. Eur. J. Pharmacol. Invited Review 15:223-232, 2015 PMID:25981304 

Nuss, A.B., Ejendal, F.K.F, Doyle, T.B., Meyer, J.M., Lang, E.G., Watts, V.J., and Hill, C.A.,  Dopamine Receptor Antagonists as New Mode-of-Action Insecticide Leads for Control of Aedes and Culex Mosquito Vectors. PLoS Neglected Trop. Diseases 9: e3515, 2015.  PMID: 25793586

Brust, T.F., Hayes, M.P., Burris, K.D., Roman D.L., and Watts, V.J. Bias analyses of preclinical and clinical D2 dopamine ligands: studies with immediate and complex signaling pathways. J. Pharmacol. Exp. Therap. 352:480-493, 2015 PMID:  25539635

Brust, T.F., Hayes, M.P., Roman D.L., and Watts, V.J. New functional activity of aripiprazole revealed: robust antagonism of D2 dopamine receptor-stimulated Gbg signaling. Biochem. Pharmacol. 93:85-91, 2015. PMID: 25449598

Conley, J.M., Meyer, J.M., Nuss, A.M., Doyle, T.B., Savinov, S.N., Hill, C.A., and Watts. V.J. Evaluation of AaDOP2 receptor antagonists reveals antidepressants and antipsychotics as novel lead molecules for control of the yellow fever mosquito, Aedes aegypti. J. Pharmacol. Exp. Therap. 352: 53-60, 2015. PMID: 25332454

Conley, J.M., Brust, T.F., Xu, R., Burris, K.D., and Watts, V.J. Drug-induced sensitization of adenylyl cyclase: assay streamlining and miniaturization for small molecule and siRNA screening applications. JoVE 83: doi: 10.3791/51218, 2014 PMID: 24514897

Conley, J.M., Brand, C.S., Bogard, A.S., Pratt, E.P.S., Xu, R., Hockerman, G.H., Ostrom, R., Dessauer, C.W., and Watts, V.J. Development of a high-throughput screening paradigm for the discovery of small molecule modulators of adenylyl cyclase: Identification of an adenylyl cyclase 2 inhibitor. J. Pharmacol. Exp. Therap. 347: 276-287, 2013. PMID: 24008337

Conley, J.M. and Watts, V.J. Differential effects of AGS3 expression on D2L dopamine receptor-mediated adenylyl cyclase signaling. Cell. Mol. Neurobiol. 33: 551-558, 2013. PMID: 23504261

Hill, C.A., Meyer, J.M., Ejendal, F.K.F, Echeverry, D.F., Lang, E.G., Avramova, L.V., Conley, J.M., and Watts, V.J. Re-invigorating the insecticide discovery pipeline for vector control: GPCRs as targets for the identification of next gen insecticides. Pestic. Biochem. Physiol. 106:141-148, 2013. 

Ejendal, K.F.K., Dessauer, C.W., Hebert, T. E., and Watts, V.J. Dopamine D2 receptor-mediated heterologous sensitization of AC5 requires signalosome assembly. J. Sig. Trans. 2012: Article ID 210324, 2012PMID: 22523680

Meyer, J.M., Ejendal, K.F.K., Avramova. L., Garland-Kuntz, E., Giraldo-Calderón, G., Brust, T.F., Watts, V.J. and Hill, C.A. A “genome-to-lead” approach for insecticide discovery: pharmacological characterization and chemical compound screening of Aedes aegypti D1-like dopamine receptors. PLoS Neglected Trop. Diseases. 6: e1478, 2012. PMID: 22292096

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.  PMID:  20016021

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.  PMID: 19028082

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.  PMID: 18524886

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.  PMID: 18029912

Watts, V.J. Adenylyl cyclase isoforms as novel therapeutic targets: an exciting example of excitotoxicity neuroprotection.  Mol. Inter. 7:70-73, 2007. (Invited Viewpoint) PMID:17468386

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