Pawlinski and Liu awarded a $1.6-million, four-year grant from NIH-NHLBI

Two UNC-Chapel Hill scientists, Jian Liu, PhD, Distinguished Professor in the UNC Eshelman School of Pharmacy, Division of Chemical Biology & Medicinal Chemistry, and Rafal Pawlinski, PhD, Professor in the Department of Medicine, Division of Hematology and Oncology, 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.

Pawlinski and Liu awarded a $1.6-million, four-year grant from NIH-NHLBI click to enlarge Dr. Pawlinski & Dr. Liu

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.

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