Xinru Chen

Research/Areas of Interest

Non-alcoholic fatty liver disease (NAFLD), a manifestation of cardio-metabolic disorder in the liver, has been rising in incidence with the epidemic of type II diabetes, obesity, and dyslipidemia in the US and worldwide. However, there are currently no approved therapeutic options that can treat or prevent this disease. Our lab recently showed that the severity of NASH and plasma LDL cholesterol levels significantly correlated with hepatocyte protease-activated receptor 2 (PAR2, F2RL1) expression in patients. Mice with whole-body PAR2 knockout had reduced expression of key genes involved in cholesterol synthesis, reduced plasma and total liver cholesterol, and increased cholesterol transport into the bile, fecal bile acid secretion, along with reductions in triglycerides, NAS score, liver ballooning, inflammation, and obesity. However, we still don’t know what’s the mechanism of PAR2 activation in NAFLD and which PAR2-expressing cell type(s) contribute to NAFLD pathology. In my thesis study, I will answer these questions using our newly established tissue-specific PAR2 knock-out mice strains: hepatocyte PAR2 KO PAR2^deltaHep and myeloid cell PAR2 KO PAR2^deltaMp. I will use RNA sequencing and single cell RNA sequencing to conduct detailed mechanisms study. My study will provide strong evidence for using PAR2 as a drug target and help inform clinical practice in the future.