Research Projects

Non-alcoholic fatty liver disease (NAFLD) is a growing metabolic disease characterized by excess hepatic fat deposition, often leading to Non-alcoholic steatohepatitis (NAsH). NAsH is a clinically alarming stage of NAFLD that can result in liver injury, fibrosis, cirrhosis, and even hepatocellular cancer. Unfortunately, there is no approved drug therapy for NAsH, and its progression may become irreversible in some individuals. Extracellular RNA (eRNA) is a heterogeneous group of damage-associated molecular patterns (DAMPs) released from hepatic injury associated with NAsH. eRNA may play a role in differentiation, chromatin modification, inflammation, and tissue injury and repair. The administration of Ribonuclease1 (RNase1), which degrades eRNA, has shown efficacy in decreasing disease severity in preclinical disease models. However, it is unknown whether eRNA plays a role in hepatic cell apoptosis and pro-inflammatory cytokine production in human NAsH and if RNase1 administration can act as an interventional strategy in reducing NAsH progression. This study aims to test the hypothesis that extracellular RNA released from injured/dead hepatocytes with lipid overload aggravates liver injury and increases pro-inflammatory cytokine production, and if RNase1 administration in NAsH may act as an interventional strategy.