Engineering new signaling biomolecules for re-directing oncogenic and immune pathways
Molecular recognitions, such as receptor-ligand binding, enzyme-substrate recognition, or metabolite-protein interaction, are fundamental processes driving all biological pathways. My laboratory’s research focuses on repurposing natural and synthetic molecular recognition events for sensing and re-directing cell signaling responses. Our research spans three interrelated directions. First, we design sensors and signaling integrators to detect the dynamic signaling events in the tumor microenvironment (TME). This research is based on coupling a molecular recognition event to a fluorescence or luminescence output. The work will lead to a deep fundamental understanding of how tumors grow and progress in situ and how they interact with the surrounding cells, molecules, or therapeutic perturbations. Second, based on the knowledge we learned about the TME, we design new biologics and signaling circuits activated only in the disease microenvironment. This research is based on devising conditional molecular recognitions such as ATP- or phospho-activated binding domains. These new molecules will address the challenge of off-tumor toxicities and low efficacy with current cancer medicines. Lastly, we develop new biomedicine modalities that can target previously intractable drug targets. This research is based on exploiting bi-specific protein recognition to engage the downstream response of one target to the other. This research will enable new strategies to functionally manipulate “yet-to-be-drugged” protein groups through novel mechanisms.