Chemical biology and drug discovery: identification of small molecules that modulate cellular signaling pathways with an emphasis on protein-protein interactions for use as biological probes and therapeutic agents.
Research interests in my laboratory lie at the interface of chemistry and biology. Our goal is to discover and develop novel molecular entities that modulate cellular signaling pathways with an emphasis on protein-protein interactions. To this end, we take a multidisciplinary approach including synthetic organic chemistry, combinatorial chemistry, medicinal chemistry, molecular biology and cell biology.
Protein-protein interactions play pivotal roles in virtually every biological process and thus are emerging as promising therapeutic targets for various diseases including cancer. However, most such interactions cannot be readily disrupted by small molecules, since protein-protein interaction sites are fairly large and shallow. To identify molecules that disrupt protein-protein interactions, we focus on the design and construction of small molecule or peptidomimetic libraries that can mimic protein secondary structures or target a compact region of protein-protein interaction, so called "hot spot", high-throughput screening of the libraries (using either forward or reverse chemical genetic approach), and functional characterization of the identified compounds. Selected lead compounds will be further elaborated structurally based on structural information such as X-ray and NMR studies to improve their potency and specificity, and evaluated functionally in vivo in collaboration with other research groups. The resulting compounds will serve as highly useful biological probes to elucidate the functions of target proteins in model systems.
