Jeffrey W. Smith

Biography

Jeffrey W. Smith earned his Ph.D. in biological sciences at UC Irvine in 1987. Following postdoctoral training at The Scripps Research Institute, he was appointed to their staff in 1991. Dr. Smith was recruited to Sanford Burnham Prebys in 1995.

Research Interest

Dr. Smith’s laboratory has a longstanding interest in developing new methods for proteomics. In particular, they have been interested in activity-based proteomics, in which small molecules are used to tag active sites within enzymes. By constructing such probes so that they react broadly with many members of an enzyme class, one can quantify and identify active enzymes within any biological sample. With this strategy, one can use the power of chemistry as a “separation tool” to parse the proteome into easily understandable classes. Because the chemical probes that are used for activity-based proteomics bind at the active site of a class of enzymes, one can also use this method to screen for drugs that inhibit a particular enzyme. Because activity-based probes usually bind to the homologues in an enzyme family, such drug screening also reveals cross-reactivity of many compounds, information that can be used to eliminate unwanted side effects of drugs. Our group used this approach to identify fatty acid synthase as a drug target in oncology, and to reveal that Orlistat, a drug already approved for treating obesity, is a lead antagonist of this enzyme.