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diagram of platelet-neutrophils

Goal: Characterize PAR4 GPCR signaling in response to cathepsin G cleavage.

Protease activated receptor 4 (PAR4) regulates platelet-neutrophil interactions in stroke ischemia-reperfusion (I/R) injury.  We have shown that neutrophil cathepsin G (CatG) amputates the thrombin tethered ligand; the resulting CatG tethered ligand induces PAR4 signaling & platelet activation.  We have on-going studies to identify the CatG tethered ligand binding site and to test both the role of CatG in stoke outcomes and the potential therapeutic benefit of inhibition CatG cleavage of PAR4.