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Two UNC scientists, Jian Liu, Distinguished Professor in the Eshelman School of Pharmacy, Division of Chemical Biology & Medicinal Chemistry and Rafal Pawlinski, Professor in the Department of Medicine, Division of Hematology and Oncology, Member of McAllister Heart Institute, have been awarded a 1.6-million, four-year grant from the NIH-NHLBI to investigate the potential therapeutic effect of new synthetic heparan sulfates in a model of drug-induced liver injury.

Acetaminophen (APAP) overdose is the leading cause of drug-induced liver failure in the United States and Europe. Drs. Pawlinski and Liu have discovered that a synthetic, 18-saccharide long heparan sulfate (18-mer) protects against APAP-induced acute liver injury in mice. Importantly, they demonstrate that 18-mer administered 6 hours after APAP overdose is still protective, and therefore may offer a potential therapeutic advantage over standard treatment with N-acetyl cysteine, which is only effective when administered within first few hours after APAP overdose. The protective effect of 18-mer is mediated, in part, by targeting high mobility group box 1 (HMGB-1) and subsequent reduction of sterile inflammation. The awarded project aims to identify further molecular mechanisms mediating the protective effects of 18-mer and will explore the hypothesis the 18-mer treatment restores the protection provided by endogenous heparan sulfate proteoglycan called syndecan-1.