Thalia Newman
Investigating Novel Targets for the Mitigation of Pathogenic NETosis in APS
Abstract
Autoantibodies targeting beta-2 glycoprotein I (anti-ß2GPI) trigger thrombosis and inflammation in antiphospholipid syndrome (APS). Anticoagulation, the standard treatment for APS, inconsistently prevents thrombosis and fails to mitigate long-term organ damage. How to combat anticoagulant-resistant APS manifestations remains unknown. We have previously shown that anti-ß2GPI activate neutrophils through Toll-like receptor 4 (TLR4) to promote the release of pathogenic neutrophil extracellular traps (NETs), which are critical for inflammation and immunothrombosis in models of APS. We recently observed that APS neutrophils transcriptionally upregulate CD14, a co-receptor for TLR4, and zDHHC19, an understudied palmitoyltransferase. Through flotillin palmitoylation, zDHHC19 may play a role in lipid raft stabilization and CD14 surface localization. We hypothesize that inhibiting CD14 and/or zDHHC19 will mitigate pathogenic APS-associated NETosis, reducing the risk of thrombosis in APS.
Being selected for the PhRMA Foundation Predoctoral Fellowship in Translational Medicine is both an honor and an investment in my development, empowering me to drive research that translates scientific insight into meaningful patient impact.
