After completing undergraduate work in Chemistry at Rutgers University, Charles Thompson received M.S. (1980) and Ph.D. (1982) degrees in Chemistry from The University of California, Riverside. Following postdoctoral appointments at Harvard University (1982-1983) and The University of California, Berkeley (1983-1985) he held a faculty position in Chemistry at Loyola University of Chicago (1985-1994). He moved to the University of Montana as an Associate Professor in 1994 and was promoted to Professor in 1996. In 2000, he became the co-Director of the University of Montana National Science Foundation (NSF) Experimental program to Stimulate Competitive Research (EPSCoR) at the University of Montana.

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INTERESTS OF THE THOMPSON LABORATORY

Research in our group uses a combination of [bio]chemical, cellular and spectroscopic approaches to solve problems in neuroscience, particularly the neurotransmitter systems, glutamate acetylcholine and glutamate. Four principal approaches a currently underway include:

1) Design and synthesis of pharmacologically active compounds to probe, regulate and inhibit neurotransmitter systems.
2) Computer-aided modeling to design, simulate and visualize pharmacophore models for receptors, enzymes and transporters.
3) Application of proteomics to neurotransmitter systems.
4) Development and applications of custom-tailored antibodies for immunologic detection in neurotransmitter systems.

Glutamate Neurotransmitter System: The primary goal of this project is to define the structural requirements for selective and potent binding to the vesicular glutamate transporter (VGLUT) protein. The long-range goal of this study is to develop a pharmacophore model of the glutamate vesicular transporter protein and utilize this information to regulate vesicular storage, uptake and release of glutamate. To date, few competitive inhibitors have been identified and therefore the principle strategy of our work is to design and synthesize new inhibitors using the structural and functional group characteristics of certain known inhibitors in combination with key features of the glutamate molecule. Once identified, the new inhibitor library will be used to develop a pharmacophore model and affinity ligands to probe the structure and function of the transporter.

Acetylcholine Neurotransmitter System: Our principle aim is to study how organophosphate (OP) insecticides may be partially or wholly responsible for an diverse array of modes of toxic action. Most OP insecticides (e.g., malathion, diazinon, chlorpyriphos, etc.) impart their toxic action by initial conversion to an oxon which then inhibits acetylcholinesterase (the enzyme responsible for the hydrolysis of the neurotransmitter acetylcholine). Following cholinesterase inhibition, the organism generally dies of complications associated with cholinergic poisoning. However, more recent evidence suggests that OP compounds may injure cells and/or covalently modify non-target proteins via non-cholinergic modes of action. Using neuronal cell culture and AChE knock-outs, our goal is to identify non-target proteins that are susceptible to OP's and to identify proteins that are up- or down-regulated in response to an OP insult
Some of the specific questions we are trying to answer in the glutamate and acetylcholine neurotransmitter system include:

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SELECTED PUBLICATIONS

Thiagaraj, H.V.; Russo, E.B.; Burnett, A.; Goldstein, E.;  Thompson, C.M.; Parker, K.K. (2005) Binding Properties of Dipropyltryptamine at the Human 5HT1a Receptor. Pharmacology (in press).

Lockridge, O., Duysen, E. G.; Voelker, T.; Thompson, C.M.; Schopfer, L.M. (2005) Life Without Acetylcholinesterase: The Implications of Cholinesterase Inhibitor Toxicity in AChE-Knockout Mice."  Environ. Tox. Pharmacol (in press).

Peeples, E.; Schopfer, L.M.; Duysen, E.G.; Spaulding, R.; Voelker, T.; Thompson, C.M.; Lockridge, O. (2005) Albumin, a New Biomarker of OP Exposure Identified by Mass Spectroscopy.  Toxicological Sci. 83: 303-312.

Tongcharoensirikul, P.; Suarez, A.I.; Voelker, T. Thompson, C.M. (2004) Effect of Chiral Auxiliaries on the Stereoselective Addition of Dimethyl Thiophosphite to Imines. J. Org. Chem. 69: 2322-2326.

Thompson, C. M., Richardson, R. J. (2004) Anticholinesterase Insecticides. In Pesticide Toxicology and International Regulation (Current Toxicology Series), Marrs, T. C. and Ballantyne, B., Eds. John Wiley & Sons Ltd, Chichester, (2004) 89-127.

Coughenour, H.D.; Spaulding, R.S.; Thompson, C.M. (2004) The Synaptic Vesicle Proteome: A Comparative Study in Membrane Protein Identification. Proteomics, 4: 3141-3155.