RESEARCH

In chemistry, an emphasis has been on understanding non-covalent interactions of complementary aromatics, leading to the creation of relatively large, folded structures and assemblies with applications in various fields.  Notable achievements include the development of the first abiotic folding systems operating in aqueous solution, the first abiotic molecules that accurately mimic the behavior of the amyloid seen in Alzheimer’s or other diseases and innovative DNA-binding molecules operating via a unique type of recognition and very tight binding referred to as threading polyintercalation.

More recently, the lab has been exploring the intentional control of two distinct aromatic stacking geometries to develop solid materials that undergo a dramatic bight orange to bright yellow color transition when heated or ground as a powder.  Students and post-doctoral fellows involved in these projects gain expertise in computer-guided molecular design, organic synthesis, manipulation and analysis of non-covalent interactions as they relate to protein folding, amyloid behavior, nucleic acid chemistry or even solid-state materials science.

On the molecular biology side of the lab, the focus is on protein engineering for therapeutic purposes. Collaborating with scientists such as Dr. George Georgiou, the lab has developed a number of powerful protein engineering technologies to enhance antibody ligand affinity and alter enzyme substrate specificity and activity.  One significant outcome is the development of Anthim™, an FDA-approved engineered antibody for anthrax prevention and late-stage cure.

More recently, the lab has developed a powerful technology referred to as YESS 2.0, capable of engineering and studying both proteases and kinases with unprecedented precision.  One goal of this work is to disrupt the current antibody-based biologics drug market by engineering proteases that cleave validated therapeutic disease targets with exquisite selectivity.  Because proteases would operate as a catalyst, we hypothesize that compared to antibodies, a protease therapeutic would require dramatically less treatment material, thereby significantly lowering costs and side-effects for patients.  Tyrosine kinases, currently represent a major and expanding class of therapeutic drug targets for a variety of diseases.

We have been using YESS 2.0 to understand the substrate specificities of tyrosine kinases of therapeutic interest at an unprecedented level of precision in an effort to develop a new generation of far more selective therapeutic kinase inhibitors.  Students and post-doctoral fellows involved in these projects gain expertise in many of the more applied biomedical aspects of therapeutic biologics as well as fundamental molecular biology techniques including cloning, protein expression and characterization, directed evolution, fluorescence activated cell sorting (FACS) and bioinformatic analysis of large datasets.