Chemoproteomic profiling using natural product-inspired probes

More than 7% of our genes encode proteins involved in the immune system. Yet, many of the processes underpinning the immune response still remain poorly understood. By applying and advancing chemoproteomic platforms combined with high-throughput and phenotypic screenings, we aim to discover functionally and therapeutically relevant target proteins for the development of immunomodulatory agents. Our approach is to use activity-based protein profiling (ABPP) with a range of chemical scaffolds, including protein-reactive natural products and covalent ligands. Particularly, electrophilic natural products that bind and covalently modify their targets through reactive functional groups offer ideal starting points for the development of chemical probes and facilitate the identification of their biological binding partners. Future goals of this project include understanding biological mechanisms of immunomodulators in the treatment of cancer and development of novel cancer immunotherapy.

Activity-based probes and inhibitors for proteases in immunity

Proteases are common constituents of endolysosomal compartments and play key roles in pathogen recognition, elimination, signal processing, and cell homeostasis in immune cells. Our research focuses on the development of chemical tools that allow kinetic and dynamic measurement of the network of protease activities. The major goal of this project is to study functional roles of proteases and how they are implicated in disease development and progression and ultimately provide potential therapeutic agents.

Chemical approaches for targeted and controlled activation of immune signaling

We are interested in understanding molecular and chemical codes that shape the immune responses. Our approach to this task is to develop methods that control the activation of specific immune cell subsets temporally and spatially and visualize the interaction of tissue-resident immune cells with their surroundings. We use a chemical caging approach combined with conjugation for localized activation of innate immune receptors and signaling.