Pilot Project Awardees
Shi-Ying Cai, PhD
Senior Research Scientist, Internal Medicine: Digestive Diseases
Project Title: Role of Ca2+/NFAT signaling pathway in cholestatic liver injury
Bile acids initiated inflammatory response plays an important role in the pathogenesis of cholestatic liver injury, yet the detailed mechanisms remain to be elucidated. My preliminary data indicates that elevated levels of bile acids cause ER-stress and mitochondrial damage and result in dysregulation of Ca2+ signaling in hepatocytes. Therefore, I hypothesize that activated Ca2+/NFAT (nuclear factor of activated T-cells, a transcription factor) signaling pathway stimulates the expression of hepatic inflammatory cytokines in cholestasis. In this pilot project, I propose to assess NFAT’s role in cholestatic liver injury by examining both hepatic expression of NFAT and inflammatory cytokines in vivo in the livers of patients with primary biliary cholangitis and primary sclerosing cholangitis and ARE-Del-/- mice (a novel model of primary biliary cholangitis) and in vitro in primary hepatocyte cultures from humans and mice. Completion of this study may reveal novel mechanisms of cholestatic liver injury and help to develop new strategies for treating cholestasis.
John Onofrey, PhD
Associate Research Scientist, Radiology and Biomedical Imaging
Project Title: Automated Hepatic Lesion Detection and LI-RADS Prediction using Deep Learning for Clinical Decision Support
Dr. John Onofrey, Assistant Professor in the Departments of Radiology and Biomedical Imaging and of Urology, was awarded a 2019 Yale Liver Center Pilot grant to develop novel machine learning methods to automatically diagnose liver cancer. The overarching goal of this project is to develop methods to incorporate both imaging biomarkers and clinical indicators into an automated clinical diagnostic aid. The innovation in this project lies in the use of deep learning to automatically predict the classification of hepatic lesions according to the Liver Imaging Reporting and Data System (LI-RADS). This project, which brings together a multidisciplinary team with expertise in diagnostic and interventional radiology, engineering, biomedical data science, and hepatology, has the potential to improve clinical efficiency and reduce variation in liver cancer diagnosis.
Jittima Weerachayaphorn, PhD
Adjunct Assistant Professor, Internal Medicine: Digestive Diseases
Project Title: Role of inositol 1,4,5-trisphosphate receptors in alcoholic hepatitis
Alcoholic hepatitis is the most severe form of alcoholic liver disease and presents with high morbidity and mortality. Emerging evidence suggests that cholestasis is a dangerous complication in alcoholic hepatitis. Cholestasis that occurs in alcoholic hepatitis is due in part to cholangiocytes and results from loss of the type 3 inositol trisphosphate receptor (ITPR3) expression in cholangiocytes. Alcoholic hepatitis is associated with a neutrophilic inflammatory infiltrate in hepatic lobules and direct cell-to-cell contact between neutrophils and cholangiocytes prerequisites for the loss of ITPR3 expression. The goal of this project is to determine how neutrophils interact with cholangiocytes to decrease ITPR3 expression and that cause cholestasis and explore the intracellular pathways that decrease ITPR3 expression in cholangiocytes when they interact with neutrophils. This study will increase our understanding of the pathogenesis of cholestasis that occurs in alcoholic hepatitis, may establish a new paradigm for a new role for neutrophils in alcoholic hepatitis, and may define new targets for the treatment of alcoholic hepatitis.