Research Interests

I am chemist who is trying to understand the molecules of the human brain. Our targets are the complex, integral membrane proteins found at the synapse, and our goal is to evaluate their structure and function with chemical-scale precision. Our major tool has been unnatural amino acid mutagenesis using the Xenopus oocyte expression system, coupled with electrophysiology. With this tool, we have been able to rationally modify neuroreceptors and ion channels in both very subtle and very dramatic ways and evaluate the impact of the modification on the function of the receptor or channel. A highlight has been the determination of the broad relevance of the cation-Pi interaction to drug-receptor interactions in neurobiology. The cation-Pi interaction is a powerful noncovalent binding force that was developed in our labs and that we have shown to be employed across all molecular sciences, from structural biology to materials science. In molecular neurobiology, we have shown that the cation-Pi interaction plays an important role in the function of receptors that respond to acetylcholine, serotonin, dopamine, GABA, and glycine, as well as potassium and sodium channels. The cation-Pi interaction also plays a prominent role in nicotine addiction, provide a key binding interaction between nicotine and specific receptors in the brain.

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Primary Section

Section 14: Chemistry

Secondary Section

Section 23: Physiology and Pharmacology