Jorge Ruas

Nonalcoholic fatty liver disease (NAFLD) is estimated to affect up to one third of the adult population in industrialized countries and 70-80% of obese patients with diabetes. The milder stage, hepatic steatosis, is often asymptomatic and undiagnosed but over 30% of these patients progress to nonalcoholic steatohepatitis (NASH). NASH impairs liver function and is a risk factor for cirrhosis, hepatocellular carcinoma, and cardiovascular disease. Amongst obese patients with diabetes, 30-50% develop NASH. There are no specific pharmacological treatments for NASH and drug development depends on a better understanding of the mechanisms underlying its pathogenesis. In addition, there are no biomarkers to diagnose and monitor NAFLD/NASH progression.We have identified a protein with previously unknown function and discovered that it operates as a major regulator of inflammation, extracellular matrix remodeling, and fibrogenesis. Based on its function, we have named it Tissue Remodeler and Activator of INflammation (TRAIN). TRAIN expression is elevated in human and rodent liver disease. We have observed that increasing TRAIN expression in mouse liver is sufficient to elicit many of the metabolic, morphological, histological, and transcriptional abnormalities characteristic of NASH. Our goal is to understand how TRAIN activation leads to NALFD/NASH, to identify reliable disease biomarkers and to develop novel therapies for NAFLD/NASH by manipulating TRAIN activity.