Area of interest
During fifteen years in the pharmaceutical industry, my experience involved the generation and use of chemical probes to elucidate biological function of understudied protein targets. Beginning in 2000, I led programs to identify chemical probes for nuclear receptors such as LXR and ERR. The generation of these probes involved identification of chemical starting points by high-throughput screening (HTS) or focused screening. Iterative medicinal chemistry for the optimization of potency, selectivity, and other parameters was guided by several methods, including structure-based design and ligand-based rational design.
In 2008, my focus turned to the understudied protein kinome. Our team defined a set of over 800 ATP competitive kinase inhibitors to engage the scientific community. We have shared these compounds openly and have enabled hundreds of collaborators. The result has been a large body of activity annotation in a wide variety of contexts. The set has served as both to identify chemical starting points for historically understudied kinases and also as to define kinases or combinations of kinases whose inhibition leads to phenotypes of interest. This set of kinase inhibitors was crucial in the establishment of and is central to ongoing activities within the SGC-UNC, a center for open science within the UNC Eshelman School of Pharmacy.
Awards and Honors
1993 Predoctoral Fellowship, National Science Foundation
1993 Chemistry Alumni Award, Grinnell College
1998 Postdoctoral Fellowship, National Institutes of Health
2000 Research Excellence Award, GlaxoWellcome