Improvements in Structural and Quantitative Lipidomics with Applications to Liver Cancer

A thorough analysis of the lipidome is a prerequisite for understanding of biochemical mechanisms of disease and drug effects. The most common method for this is LC-MS.

However, there are a number of analytical challenges to meet in order to obtain refined biochemical information beyond the capability of today’s methods.

Lipids with accessible phosphates, such as cardiolipins, yield severely distorted peaks in reversed-phase LC (RPLC) hampering their analysis. Regioisomers and enantiomers of glycerolipids co-elute in RPLC.

Separate determination of these isomers would provide important information on the regulation of certain biochemical pathways. Furthermore, only relative quantifications or semi-quantifications are available today. Absolute quantifications would provide a deeper understanding of the regulation of the lipidome.

We will address all these analytical challenges in this project. We will use new buffers for improved peak shapes, 2D LC-SFC for chiral separation.

The regioisomerism of glycerolipids will be determined by MS fragmentation in combination with ion-mobility and chemoinformatics.

In order to enable quantitative analysis, we will model the response of a number of selected standards and then predict the response of other lipids.We will apply our novel analytical tools to cellular models, organoids and murine models of hepatocellular carcinoma, to draw refined conclusions on the mechanism of anthracyclin-induced cell death.