LiSyM - Liver Systems Medicine

Chronic liver diseases (CLD) are caused by chronic injury through different insults, e.g. high caloric diet and chronic alcohol consumption. They trigger chronic inflammation, which induces a fibrogenic response involving parenchymal and non-parenchymal liver cells. CLD progression leads to cirrhosis and ultimately cancer, organ failure and death. Because of the complexity of this scenario, a systems medicine approach is chosen to develop strategies to better characterize progression and resolution of fibrosis. Hence, Pillar II „Disease Progression“ aims to define key molecular mechanisms and structural changes in tissue architecture during CLD by visualizing and quantifying at cellular, tissue and organ scale. Translation into clinical practice is hampered by complex disease dynamics and multidimensional cell-cell communication. Therefore, the dynamics and multifarious interactions during possible disease scenarios on different scales will be analyzed, quantified, and combined with iterative mathematical modeling approaches. Such models will allow optimized disease staging, prediction of progression and resolution, as well as to define new therapeutic and diagnostic targets.

The ICB will develop methods for multi-omics integration and subsequent pathway analysis for whole and phosphoproteome, secretome, transcriptome and methylome data in order to identify key molecular alterations in ACL.

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