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'Silent killers'. This is how liver diseases are often described. But, are they really that silent? ERC grantee Mathieu Vinken, a pharmacist by training and worldwide expert in toxicology based at Vrije Universiteit Brussel (VUB), has just proven the contrary.

The liver: that large organ situated on the right side of your belly in charge of filtering blood, detoxifying the body and balancing energy metabolism, among other vital tasks. Although the liver is strong and has a great capacity to regenerate, liver diseases represent the fifth main cause of mortality in the world and remain a great concern for public health. Understanding the mechanisms of these conditions is essential for the development of clinical treatments and early diagnosis. That is exactly what Mathieu Vinken does within his EU-funded project CONNECT.

"Like people, our body's cells interact and communicate with each other to function and accomplish their daily tasks", explains Vinken. "In disease conditions, however, this whole communication falls apart, but there is more to it", he says.

Breaking bad

What Vinken and his team members have found, is that in certain forms of acute liver toxicity as well as in chronic pathologies, such as liver fibrosis and non-alcoholic steatohepatitis, liver cells initiate a "different type of conversation".

During illness, such as in liver disease, cells start to communicate via so-called hemichannels, which are otherwise closed in healthy circumstances” says Vinken.

While it is not yet clear how exactly and why these hemichannels open up, Vinken's research team has been the first to prove the existence of this harmful form of cell communication, which leads to inflammation and cell death, in liver. When health is compromised, this general mechanism can also be observed in other body organs.
Hence, Vinken's findings could represent a major step forward in tackling other widespread conditions that are also associated with inflammation and cell death, including cardiovascular and brain diseases.

To study this specific type of cell communication, the team worked both in vitro, using cultures of liver cells, and in vivo, using human-relevant mouse models of liver disease. The focus is now on developing specific drugs that will shut down hemichannels. And the first results are extremely promising.

From the bench to the clinic

Bridging the gap between fundamental research and the pharmaceutical industry is the next step", says Vinken. For his ERC-funded findings, he has just received the Galenus award, praising major advances in pharmaceutical research. Beyond this important recognition, the research project opens a promising path for people with liver pathologies and could lead to new drugs and clinical treatments in the years to come.

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