Basic research is a major part of my career, currently accounting for about 70-75% of my total effort. For nearly two decades, my research has focused on the mechanisms responsible for general anesthesia, particularly their actions at fast neurotransmitter-gated ion channels, which are responsible for neuron-to-neuron synaptic communication. Currently, my lab is studying anesthetic actions on both nicotinic acetylcholine receptors, which are responsible for excitatory transmission in nerve and muscle, and gamma-aminobutyric acid type-A receptors, which are responsible for inhibitory neurotransmission in the brain and spinal cord. To investigate both how and where anesthetics affect the function of these ion channels, my research combines electrophysiological techniques with recombinant ion channel expression. I have pioneered advances in ultrafast superfusion of excised patches and patch-clamp electrophysiology by developing methods and building equipment for sub-millisecond switching among up to four independent flowing superfusates in an "artificial synapse." This advance has enabled demonstration of novel mechanisms of drug action. By creating mutations in specific protein regions of recombinantly expressed ion channels in living cells, my research has tested hypotheses about sites of anesthetic action. I was the first investigator to provide solid evidence for such a site on a ligand-gated ion channel, and the rigorous demonstration of these sites on receptors in brain remains a major thrust of my current research. My current research also includes collaborative projects with scientific colleagues in and outside my department. My research has been funded by the Foundation for Anesthesia Education and Research, the Medical Foundation/Charles King Trust, as well as a Scientist Training Award (K21) and Individual (P01/R01) Awards from the National Institutes of Health. I have been invited to present my research at regional, national, and international meetings. In 2004 I was awarded a Presidential Early Career Award for Scientists and Engineers (PECASE) for my research. I serve as an ad hoc reviewer for a number of scientific journals. As a member of the Dept. of Anesthesia Executive Committee on Research and the Beecher/Mallincrodt Research Laboratories Executive Committee, I have dedicated time to encouraging and supervising research activities within our department and mentoring young researchers, including students, residents, and research fellows.

Anaesthesia Pharmacology Pharmacology of Nitrous Oxide General Anesthetic Sites in GABA-A Receptor Subunit Interfacial Pockets Volatile Anesthesia and the GABAA Receptor Gamma Subunit NICOTINIC RECEPTOR SITES FOR ALCOHOL ACTIONS   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