Stuart A. Forman, MD, PhD
Associate Professor, Harvard Medical School
Vascular Anesthesiology, Thoracic Anesthesiology, Combined Epidural and General Anesthesia
My research focuses on the molecular pharmacology and mechanisms of actions of general anesthetic agents. The most likely molecular targets for these agents are neurotransmitter-activated ion channels. We study muscle and neuronal nicotinic acetylcholine receptors (nAChRs), gammaaminobutyric acid type A receptors (GABAARs), serotonin receptors (5-HT3A-Rs), and other channels.
We study recombinantly expressed cloned receptors using electrophysiology in both xenopus oocytes and cultured mammalian cell expression systems. Some data is obtained using the two-electrode
oocyte clamp technique. Detailed kinetic studies of the rates of receptor activation, desensitization, and deactivation are performed using patch-clamp electrophysiology in combination with techniques for ultrafast (sub-millisecond) superfusion solution exchange.
The general hypothesis underlying my research is that anesthetics interact directly with neurotransmitter receptor proteins at sites that mediate their functional effects. We use a structure-function approach for both forward and reverse pharmacology. In forward pharmacology, we study structure-activity relationships among a number of anesthetic molecules from various classes. In reverse pharmacology, we make structural changes to putative sites on neurotransmitter receptors (using site-directed mutagenesis or chimeric subunit constructs) and study how they alter sensitivity to anesthetics.
Harvard Medical School, MD, PHD
Keith Miller, D.PHIL. Profile
Pharmacology of Anesthesia
Department of Anesthesia, Critical Care and Pain Medicine
55 Fruit Street
Boston, MA 02114