Could you tell us about the career path that led you to your current position and research interests?
I suppose anxiety was one of the early motivators in my career; more specifically, the study of the role of GABAA receptors in the development of anxiety disorders, ranging from generalized anxiety to post-traumatic stress. As a post-doctoral fellow, I worked with then MD/PhD student Dennis W. Choi and Gerald D. Fischbach in the Department of Pharmacology at Harvard Medical School to uncover the cellular mechanisms of action of benzodiazepines-the class of agents that serve not only as anxiolytics, but sedative hypnotics and anticonvulsants as well. We showed that benzodiazepines act by positive allosteric modulation of GABAA receptors [1], and we provided the first measurement of the synthesis, degradation and turnover of a neurotransmitter receptor in the central nervous system [2]. My research today continues to be primarily focused on the discovery and development of neuromodulators as therapeutic agents, and on the structure, function, and cellular dynamics of ion channels and receptors in the brain and spinal cord [3]. For example, we have shown that the endogenous neuroactive steroid pregnenolone sulfate, which is formed from cholesterol via sulfotransferase action on pregnenolone, creates a branch point for activation of an allosteric modulator of NMDA and non-NMDA glutamate receptor function [4]. We have recently reported that this unique sulfated steroid can stimulate the trafficking of functional NMDA receptors to the cell surface via a non-canonical G-protein and Ca++-dependent mechanism, a finding that may further the development of treatments not only for schizophrenia, but also for other conditions associated with malfunctioning NMDA receptors, such as age-related decreases in memory and learning ability [5].