Pillar research

LiSyM research is based on four pillars

The liver is a versatile organ in which hundreds of complex processes occur simultaneously. For this reason, we have divided our program into four sub-components - the LiSyM Pillars. In these pillars, researchers from the different disciplines work closely with clinical scientists and mathematical modelers. Scientists from the different pillars also collaborate. This structure enables LiSyM to cooperate in multidisciplinary research projects, which are needed to understand the many ways the metabolic liver disease NAFLD affects the liver on all scales - from cells, molecules and genes to the entire organ.

Pillar I: Early Metabolic Injury

When does a fatty liver really develop a disorder?

One of the tasks of the healthy liver is to store fat. Yet, at some stage, too much fat makes the liver sick. One critical time point occurs when a healthy fatty liver becomes inflamed and progresses to steatohepatitis, or NASH.
LiSyM-Pillar I will identify what events lead to this transition. Does it occur in all parts of the liver? Which molecules indicate that it is taking place? Can the degeneration be stopped or undone - and if so, how?

Pillar II: Chronic Liver Disease Progression

When connective tissue replaces functioning liver cells

In one in five people with NAFLD, the functioning liver cells, the hepatocytes, are replaced by connective tissue. Eventually this fibrosis becomes irreversible. In this state the liver is like a ‘scar that never heals’. Through it, the liver loses many of its vital functions.
LiSyM-Pillar II wants to know more about which factors promote fibrosis and the conditions under which fibrosis becomes irreversible How can fibrosis be diagnosed as early as possible? Researchers in the pillar are also developing anti-fibrotic drugs, but these are not yet available.

Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure

When the liver fails after a long illness

In chronic diseases, at some point the liver can suddenly stop functioning. This is called acute-on-chronic liver failure, or ACLF. This is the leading cause of death in liver patients and is often provoked by the use of transcription or freely available drugs or alcohol abuse. For this condition we need an effective treatment quickly.
LiSyM-Pillar III researches the factors that contribute significantly to ACLF. What exactly happens then? Are there any early signs that would enable ACLF to be prevented? Can the liver be repaired or regenerated after ACLF?

Pillar IV: Liver Function Diagnostics

Detect with the computer as soon as liver function changes

Disorders of the liver show up through changes in blood tests. These blood tests indicate markers for events taking place in the liver. Usually studies of liver tissue cannot be performed: as liver samples would need to be obtained through a liver biopsy, and this procedure is not without risk, therefore these samples are usually unavailable. Complex metabolism models based on existing and new scientific data can simulate changes in the liver caused by disease. They often reveal unknown relationships and interactions clearly.
Thus, LiSyM-Pillar IV is developing new computer-aided diagnostic tools. What indicates that diseases are looming? Which tests bring this to light? Do functions also change regionally in the liver?