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The Hamm Laboratory investigates the molecular mechanisms of G protein-coupled receptor (GPCR) signaling and how these pathways regulate physiology and contribute to human disease. Building on decades of work defining the fundamental mechanisms of heterotrimeric G protein signaling, our research now integrates molecular pharmacology, chemical biology, biochemistry, cellular signaling, and disease models to translate mechanistic discoveries into potential therapeutic strategies.

A major focus of the laboratory is protease-activated receptor 4 (PAR4), a thrombin-activated GPCR with important roles in platelet activation, thrombosis, inflammation, and vascular disease. We are developing and characterizing novel PAR4 antagonists and using these pharmacological tools, together with genetic models, to define the contribution of PAR4 signaling to cardiovascular disease and vascular complications associated with disorders such as Alzheimer’s disease and kidney injury.

The laboratory also investigates G protein βγ (Gβγ) signaling in the nervous system, particularly the direct interaction between Gβγ and the SNARE complex that regulates synaptic vesicle fusion and neurotransmitter release. Using biochemical, cellular, structural, and protein-engineering approaches, we seek to better understand this signaling interface and develop new tools for selectively manipulating Gβγ–SNARE signaling.

Together, these studies connect fundamental mechanisms of G protein signaling with drug discovery and disease biology, with the goal of identifying new ways to therapeutically modulate GPCR signaling while preserving normal physiological function.