Mechanism-Based Drug Discovery and Chemical Biology

The Laboratory of Molecular Therapeutics and Chemical Biology focuses on mechanism-driven drug discovery through an interdisciplinary approach that integrates molecular design, chemical biology, and pharmacology. Our research aims to investigate disease associated molecular mechanisms and develop small-molecule strategies to modulate challenging biological targets. We are particularly interested in opportunities that extend beyond conventional approaches to drug discovery, including unconventional binding sites, complex molecular interactions, and alternative mechanisms of target modulation.

Our research combines structure-guided molecular design, computational modeling, chemical synthesis, cellular studies, and in vivo pharmacology to establish relationships between molecular structure, target engagement, and biological function. We explore diverse strategies, including allosteric and bitopic ligand design, polypharmacology, targeted protein degradation, and small-molecule modulation of protein-protein interactions. These approaches allow us to investigate novel ways to modulate biological targets, with the goal of improving selectivity, efficacy, and other pharmacological properties.

Our current research applies these strategies to opioid receptor pharmacology and cancer-associated molecular pathways. Although these areas involve different biological systems, both provide opportunities to investigate how small molecules can influence biological function through distinct mechanisms of action. We use small molecules not only as potential therapeutic candidates but also as chemical tools to investigate biological mechanisms, validate molecular targets, and identify new approaches for therapeutic intervention.

Central to our research philosophy is an iterative process in which structural insights guide molecular design, experimental studies reveal biological mechanisms, and functional outcomes inform subsequent optimization. By connecting molecular discovery with disease-relevant biology through interdisciplinary collaborations, our laboratory aims to advance innovative therapeutic strategies that address limitations of conventional treatments.