Applied and Translational Research
Although a majority of my group’s research has focused on solving fundamental questions concerning the connection between macromolecular structure/function relationships and biology, we have also established a track record in developing innovative solutions to technical problems and in addressing practical issues, such as defining small molecule inhibitor mechanisms. For example, we helped co-develop (with Prof. Steve Quake, Stanford) the first microfluidic device for crystallizing nano-volume solutions of proteins and/or nucleic acids by free-interface diffusion, and have more recently (with Prof. Axel Brunger, Stanford) expanded on this method to develop microcrystal harvesting devices for use at synchrotron and XFEL sources. We created a high-throughput screening approach to trapping protein/DNA complexes through disulfide bond formation, and developed a novel fluorescent reporter for monitoring DNA supercoiling status in real time. We also have determined co-structures of certain nucleic acid-dependent motors bound to clinically used drugs. We anticipate continuing with these types of efforts as the need and opportunity arise, particularly in conjunction within the Chemical Therapeutics Program at the S. Kimmel Comprehensive Cancer Center, which I presently co-direct with Dr. Jun O. Liu.