Massachusetts General Hospital
55 Fruit St.
Boston, MA 02114
- M.D.; Ph.D., Harvard Medical School
- Residency, Massachusetts General Hospital
- Fellowship, Massachusetts General Hospital
American Board Certifications
- Anesthesiology, American Board of Anesthesiology
Accepted Insurance Plans
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- Molecular Mechanisms of General Anesthetics
- Structure and Function of Ligand-gated Ion Channels
- Allosteric Drug Mechanisms
- Kinetic Models for Ion Channel function
- New General Anesthetic Drug Development
Description of Research
My research aims are to understand where and how general anesthetics act at the molecular level in order to help design better drugs for use in clinical settings. The molecular targets studied are anesthetic sensitive pentameric ligand-gated ion channels, including g-aminobutyric acid-A (GABAA), glycine, nicotinic acetylcholine, and serotonin receptors. Of greatest interest are potent intravenous agents including etomidate, propofol, alphaxalone, and barbiturates. We express cloned channels in cells and use electrophysiological methods to study channel function. We developed a unique 'artificial synapse' technique for high-resolution kinetic studies. Based on an allosteric co-agonist mechanism that we established for etomidate and propofol, we conduct structure-function studies in mutant receptors. We are also mapping out binding sites for anesthetics using substituted cysteine accessibility methods that combine electrophysiology with real-time chemical modification of receptors. In collaboration with Keith Miller, DPhil and Doug Raines, MD, my group also contributes to research on new photo-reactive general anesthetics, production of GABAA receptor protein for photolabeling, and development of new general anesthetics for clinical use.