WFU Physics Colloquium

TITLE: Chemoproteomic discovery of novel serine hydrolase targets in platelets

SPEAKER: Professor Leslie V. Parise

TIME: Wednesday March 23, 2016 at 4:00 PM

PLACE: Room 101 Olin Physical Laboratory

Activated platelets are critical for both normal blood clotting (hemostasis) and pathological thrombotic diseases typified by myocardial infarction and ischemic stroke. Therefore, a comprehensive understanding of complex networks controlling platelet activation is necessary for the identification of new therapeutic targets. To identify new targets, we used a chemoproteomic approach called activity-based protein profiling to identify a novel regulator of human platelet activation called arylacetamide deacetylase-like 1 (AADACL1 or NCEH1), an ether lipid hydrolase never before described in human platelets. We have shown that AADACL1 hydrolyzes an ether lipid substrate and that this substrate or a small molecule inhibitor of AADACL1 blocks platelet aggregation and thrombus formation ex vivo and in whole animal models. We also show how this lipid substrate may inhibit platelet function via interaction with specific protein kinase C isoforms that affect key signaling pathways in platelets. Thus, AADACL1 or its substrates represent novel targets for inhibiting thrombotic events.