Core 1: Metabolomics

PROJECT SUMMARY – CORE 1 The liver is of central importance to whole-body metabolism, with major roles, among others, in glucose and fatty acid metabolism, and cholesterol and bile acid synthesis. Excess nutrition leads to the development of aberrant fat deposition, which contributes to metabolic stress and the potential for progression of liver disease to

hepatocellular carcinoma (HCC). Study of metabolism is therefore of great relevance for understanding the development of HCC and is a central theme within this P01 application. Core 1 will support the metabolic research in Projects within this program both by providing an analytical service and by provision of expert advice

on the design of experiments and interpretation of results. Core 1 will quantify metabolites and measure the stable isotope content (labeling) of metabolites in cells and tissues, and will use the labeling data to calculate metabolic flux. Areas of metabolism of specific interest are glycolysis, the pentose phosphate pathway, TCA

cycle, fatty acid synthesis, cholesterol, oxy-sterol, bile acid and hexosamine metabolism. These assays will be implemented for in vitro cell and tissue slice cultures, and in vivo, with analysis of liver, tumor, and plasma specimens. Through these studies, we aim to contribute to knowledge of the metabolic landscape of HCC, and

how by differing from normal metabolism it might offer avenues for therapeutic intervention leading to improved HCC treatment.