Many modern drugs were discovered using high-throughput phenotypic screening approaches. Historically, the subsequent identification of cellular targets of the screening hits has been cumbersome and inconsistent, thus holding back their development into promising drug candidates. Recent progress in mass spectrometry-based chemoproteomics, a highly interdisciplinary and rapidly emerging research area our laboratory is specialized in, made the target identification step much more manageable. Chemical probes and their cellular targets discovered by chemoproteomics can be used to investigate the disease involvement of certain biological pathways and concomitantly serve as leads for clinical drug development.
Broadly speaking, our laboratory is working at the interface of synthetic chemistry, biochemistry and proteomics. We seek to develop chemical tools and mass spectrometry-based platforms for chemoproteomics-enabled target identification and drug discovery with a specific focus on proteins of high therapeutic promise that are currently considered “undruggable".
Chemoproteomic probe and method development
We are developing new chemoproteomic probes and platforms for target identification. We are particularly interested in hypervalent iodine-based reagents and their application as bioorthogonal chemoproteomic probes.
Natural product target identification
We are applying our probes and methods to identify and biochemically characterize the molecular targets of natural products with intriguing bioactivities with the goal of understanding their molecular mechanism of action.
Chemoproteomics-enabled drug discovery
We are evolving novel synthetic routes that allow rapid access to structurally diverse collections of small molecules, screen these small molecules in various disease models of interest, and identify their targets using our in-house chemoproteomic profiling methods.
Small MW tags for transporter mediated cellular delivery
We are designing and synthesizing small MW covalent-reversible tags which bind to specific cell surface proteins and enable cellular delivery of impermeable cargos such as peptides, proteins and nucleic acids (tags for transporter-mediated cellular delivery).