Jaehyung (Gus) Cho, PhD

Professor, WashU Medicine

Mechanisms of platelet and neutrophil activation in thrombosis and inflammation

Using intravital microscopy with tissue-specific conditional knockout mice, we demonstrated that extracellular protein disulfide isomerase (PDI, a prototypic thiol isomerase) and its signaling promote platelet and neutrophil adhesive functions by facilitating thiol exchange in cell surface adhesion receptors and enhancing their ligand-binding activities in arterial thrombosis and vascular inflammation (Hahm et al. Blood 2013; Kim et al. Blood 2013; Kim et al. Blood 2015; Li et al. Circulation 2019). We have further identified a key oxidase regulating PDI activity and are investigating its role in platelet and neutrophil functions in numerous vascular diseases. It is known that PDI and its oxidase are abundantly expressed in the brain tissue and that PDI plays a crucial role in the pathophysiology of sporadic Parkinson’s or Alzheimer’s disease (Uehara et al. Nature 2006). In collaboration with investigators at the Hope Center, I would like to study the roles for PDI and its regulator(s) in ischemic stroke and other neurodegenerative diseases. Our study using conditional knockout mice and specific inhibitors generated by my lab may provide insight into the development of a novel therapeutic agent for treating patients with neurological disease.

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