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Professor Berend Isermann has been awarded an ERC Advanced Grant by the European Research Council in recognition of the high relevance of his scientific work. The award is endowed with around 2.5 million euros and is one of the most prestigious research funding programmes in Europe. The Professor of Laboratory Medicine at Leipzig University is investigating the molecular mechanisms underlying thrombo-inflammation, as they occur frequently and can be life-threatening, yet lack specific treatment options. Thrombo-inflammation is a pathological process that occurs when the balance between blood clotting and inflammation gets out of control.
“Tame thrombo-inflammation” is the title of the successful proposal submitted by Professor Isermann to the European Research Council. “For most people, the term ‘thrombo-inflammation’ sounds very abstract, but it plays a role in almost all diseases. The coronavirus pandemic was a good example of this. In the case of COVID-19, the viral infection itself was not the problem. People died from the complications, largely from thrombo-inflammation. This catastrophic experience made us realise that we do not have a treatment for thrombo-inflammation,” says Professor Isermann.
When we fall ill, or when a wound heals, two processes are always activated: inflammation and coagulation. “The desire to better understand these mechanisms has been with me throughout my career. During pregnancy, for example, thrombo-inflammation occurs in the placenta. It’s a part of pregnancy. But if it gets out of control, then patients can suffer from pre-eclampsia, for example. I later studied the topic in chronic illnesses – such as kidney disease, heart disease and diabetes.” In thrombo-inflammation, the immune system and the coagulation cascade are activated and reinforce each other. When these processes get out of control, as they did with COVID, the result is unchecked inflammation and a tendency for the blood to clot – which can be fatal.
So far, no central molecular mechanism has been found that controls both processes. “Looking at the process from an evolutionary perspective, it is clear that there was originally one cell that controlled both. The genetic separation of the process into coagulation and inflammation came later. However, there is one factor that is different – it is called tissue factor. This is the only coagulation factor that has a different origin,” explains the medical laboratory specialist from Leipzig.
Professor Isermann’s team recently demonstrated a new property of tissue factor in the kidney. The scientists were able to show that tissue factor directly forms a complex with an important inflammatory regulator. This complex is a molecular switch that can “turn on” or “turn off” thrombo-inflammation. “This molecular switch is like a keystone in an arch which brings the two together – inflammation and coagulation. This is exactly the molecular mechanism that we have been looking for for years and that regulates both at the same time,” says Isermann. Researchers have found this activated switch not only in various kidney diseases, but also in heart attacks in animal models, in patients with severe COVID and in patients with autoinflammatory syndromes. The findings were published in a high-impact journal at the beginning of 2024. “This means that if I can turn off this switch, I might also be able to control these diseases,” says Professor Isermann.
Professor Isermann and an interdisciplinary team at the University of Leipzig Medical Center will use the ERC Advanced Grant to investigate this molecular switch over the next five years. Research questions will include: how is the switch regulated? What does the switch control at the cellular level? What is the significance of the switch in mouse models of heart disease, obesity or cancer? The team plans to pursue scientific approaches that include the further development of analytical methods to measure the switch in humans and link it to disease progression, as well as the development of new therapeutic approaches that regulate this molecular switch. “I am very confident that we have found a switch that plays an important role in thrombo-inflammation in various diseases. If we succeed in demonstrating this with our great team from the various departments at the University of Leipzig Medical Center, and perhaps also in developing therapeutic approaches, then that would be a milestone,” says Professor Isermann.
Berend Isermann studied medicine in Würzburg (Germany), Bristol (England) and New Haven (US). After gaining his licence to practise medicine at Heidelberg University Hospital, he spent five years as a researcher at the Blood Research Institute in Milwaukee (US). Back in Heidelberg, he qualified as a specialist in internal medicine, endocrinology and laboratory medicine, as well as a diabetologist and clinical chemist. He was appointed Professor of Laboratory Medicine at the University of Magdeburg in 2011 and Professor of Laboratory Medicine at Leipzig University in 2019.
Professor Berend Isermann
Professor of Laboratory Medicine, Leipzig University
Director, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig Medical Center
Email: berend.isermann@medizin.uni-leipzig.de
Tel.: +49341-9722200
Professor Berend Isermann.
Christian Hüller
Universität Leipzig
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