Professor, Department of Pharmacology
School of Medicine
Michael Hooker Chair Protein Therapeutics and Translational Proteomics Professor
Division of Medicinal Chemistry and Natural Products School of Pharmacy
Director, NIMH Psychoactive Drug Screening Program
M.D., Ph.D.
St. Louis University School of Medicine
and Department of Biochemistry
G-protein coupled receptors (GPCRs) represent one of the most evolutionarily diverse superfamilies of the human genome. My lab studies all aspects of GPCR structure and function ranging from the atomic-level analysis of ligand-receptor interactions to in vivo studies. Currently we are focused on members of the serotonin (5-hydroxytryptamine; 5-HT) and opioid receptor families and their accessory proteins.
Drug Discovery
We are actively engaged in drug discovery efforts via the shared resources of the National Institute of Mental Health's Psychoactive Drug Screening Program. Our goals are to discover and develop novel small molecule probes for in vitro and in vivo validation of molecular targets for therapeutic drug discovery. We have particular strengths with GPCR and ion-channels and are gradually expanding our capabilities to, eventually, screen the receptorome (the entire complement of receptors in the genome) and kinome (the entire complement of kinases in the genome) in massively parallel screening campaigns (see figure).
Recent Publications:
Armbruster, B.N., Li, X., Pausch, M.H., Herlitze, S., and Roth, B.L. (2007)
Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand.
Proc Natl Acad Sci USA 104(12): 5163-8. Abstract
Roth, B.L. (2007) Drugs and valvular heart disease.
N Engl J Med 356(1):
6-9. Abstract
Vortherms TA, Mosier PD, Westkaemper RB, Roth BL. (2007) Differential Helical Orientations among Related G Protein-coupled Receptors Provide a Novel Mechanism for Selectivity: Studies with Salvinorin A and the {kappa}-Opiod Receptor.
J Biol Chem 282(5): 3146-56. Abstract
Sheffler, D.J., Kroeze, W.K., Garcia, B.G., Deutch, A.Y., Hufeisen, S.J., Leahy, P., Bruning, J.C., Roth, B.L. (2006) p90 ribosomal S6 kinase 2 exerts a tonic brake on G protein-coupled receptor signaling.
Proc Natl Acad Sci USA 103(12): 4717-22. Abstract
Goldberg, M.S., Pisani, A., Haburcak, M., Vortherms, T.A., Kitada, T., Costa,C., Tong, Y., Martella, G., Tscherter, A., Martins, A., Bernardi, G., Roth, B.L., Pothos, E.N., Calabresi, P., and Shen, J. (2005) Nigrostriatal Dopaminergic Deficits and Hypokinesia Caused by Inactivation of the Familial Parkinsonism-Linked Gene DJ-1. Neuron 45(4): 489-96. Abstract
O'Connor, K.A., and Roth, B.L. (2005) Finding new tricks for old drugs: an efficient route for public-sector drug discovery. Nat Rev Drug Discovery 4(12): 1005-14. Abstract
Elphick, G.F., Querbes, W., Jordan, J.A., Gee, G.V., Eash, S., Manley, K., Dugan, A., Stanifer, M., Bhatnagar, A., Kroeze, W., Roth, B.L., and Atwood, W.J.(2004) The human polyoma virus, JCV, uses serotonin receptors to infect cells. Science 306(5700): 1380-1383. Abstract
