Massachusetts General Hospital

BiographyI have been a member of the Harvard Medical School community as a student, clinician, researcher, and teacher.  My current roles include Staff Anesthesiologist at MGH, Investigator on several NIH-sponsored basic research grants, Ad hoc reviewer for NIH grants (Surgery Anesthesia and Trauma study section), OR administration, Chair of the DACCPM Grand Rounds Steering Committee, Subcommittee Chair for HST medical admissions, Co-director of HST150 (Principles of Clinical Pharmacology), and several scientific subcommittees of the American Society of Anesthesiologists. I am an Associate Professor of Anaesthesiology at Harvard Medical School and an Associate Anesthetist at MGH.

BA-- Chemistry, Wesleyan University
MD-- HMS/MIT Health Sciences and Technology Division
PhD-- Biophysics, Harvard University
Internship-- Internal Medicine, Beth Israel Hospital, Boston
Residency-- Anesthesiology, Mass General Hospital
Fellowship-- Neurobiology, Harvard Medical School

Research

Research Areas

• 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 atthe molecular level in order to help design better drugs for use in clinicalsettings. The molecular targets studiedare anesthetic sensitive pentameric ligand-gated ion channels, including g-aminobutyricacid-A (GABA_A), glycine, nicotinic acetylcholine, and serotoninreceptors. Of greatestinterest are potent intravenous agents including etomidate, propofol,alphaxalone, and pentobarbital. We expresscloned channels in cells and use electrophysiological methods to study channelfunction. We developed a unique@artificial synaps? technique for high-resolutionkinetic studies.  Based on an allostericco-agonist mechanism that we established for etomidate and propofol, we conductstructure-function studies in mutant receptors. We are also mapping out binding sites for anesthetics using substitutedcysteine accessibility methods that combine electrophysiology with real-timechemical modification of receptors. Incollaboration with Keith Miller, Phd and Doug Raines, MD, my group alsocontributes to research on new photo-reactive general anesthetics, productionof GABA_A receptor protein for photolabeling, and development of newgeneral anesthetics for clinical use.

Publications

View my most recent publications at PubMed