Thomas Baumert: Researching Innovative Solutions for Fibrosis and Liver Cancer

Caused by viral hepatitis, fatty liver disease, or alcoholism, liver cancer is one of the deadliest in the world, responsible for nearly 1 million deaths each year. In order to combat this disease, it is essential to fully understand the cellular pathways involved. This is what Thomas Baumert – doctor, researcher and entrepreneur – has been dedicating his research to for more than 20 years, with new therapeutic avenues on the horizon...

Thomas Baumert © Inserm/E. Begouen
Thomas Baumert © Inserm/E. Begouen

Thomas Baumert* is a tireless researcher. The recipient of a number of prizes for the quality of his research into liver diseases, including the 2014 Galien Prize and the 2020 Académie des Sciences Mémain-Pelletier Prize, this is the fourth time that he has been awarded European Research Council (ERC) funding. « These 2.5 million euros will enable me to expand my research team committed to the FIBCAN program** aimed at developing new preventive or curative treatments for fibrosis and liver cancer. »

Chronic hepatitis of viral origin, alcoholism, or non-alcoholic steatohepatitis (also known as fatty liver disease, linked to a lack of exercise and to an unsuitable diet) promote the development of liver fibrosis. A condition which, when left untreated, progresses towards cirrhosis followed by hepatocellular carcinoma – a cancer with a particularly poor prognosis. « Although these liver diseases that have the potential to progress to cancer are different, the molecular processes they trigger actually have things in common. And this is a very interesting observation because it implies that a single treatment capable of preventing tumor progression by blocking these molecular pathways could be offered for each of these different diseases.

Molecular atlas

Baumert has been working on liver cell function for almost 20 years. A trained hepatologist, he began his career in Germany before setting off to perfect his clinical research knowledge in the US at the labs of Harvard and the National Institutes of Health (NIH) before returning to Fribourg to complete his clinical journey and found a laboratory dedicated to the molecular pathogenesis of liver diseases. It was in 2006 that the doctor and researcher joined Université de Strasbourg where he founded a new Inserm unit. Since then, he has headed up the Institute of Viral and Liver Disease as well as the HepSYS laboratory of excellence in Strasbourg. « Our approach differs in the techniques used and the importance given to translational research. What we want is to be able to offer clinical applications as quickly as possible following a fundamental discovery.

With partner teams at the Strasbourg University Hospitals and the Max-Planck Institute in Fribourg, he recently established a precise atlas of the biology of healthy and cancerous liver cells by sequencing single-cell RNA collected from patients and control subjects: « This has helped to elucidate the origin and development of the various liver cells, as well as how they interact, » he explains. Using samples taken from patients, the researchers were also able to assess how cancerous liver cells modify their microenvironment and lead healthy cells to modify their functioning. All in all, this work provides a comprehensive overview of the molecular mechanisms governing liver cell architecture and function, in physiological and pathological situations. A valuable basis for considering innovative treatments.

Des cellules infectées par le virus de l'hépatite C accumulent de grosses gouttelettes lipidiques, un phénomène appelé stéatose qui contribue au développement d'une fibrose du foie.
Hepatitis C‑infected cells accumulate large lipid droplets, a phenomenon called steatosis that contributes to the development of liver fibrosis in patients with chronic hepatitis C. © Inserm/Philippe Roingeard

Claudin‑1: an interesting protein

Thanks to this new European funding, Baumert plans to explore a cellular pathway of interest: that of claudin‑1 (CLDN1). « The ERC funding I obtained in the past had enabled us to describe the importance of this protein in the mechanism of hepatitis C virus (HCV) entry and dissemination within the liver cells. As such, we have studied its potential as a therapeutic target in the treatment of chronic HCV infection. However, it has emerged from this research that claudin‑1 itself induces signals promoting fibrosis and tumor progression. This is an important element because until now cancer has been primarily mentioned as a consequence of chronic inflammation and fibrosis of the liver. In reality, specific molecular pathways exist. Targeting CLDN1 could therefore be useful in preventing liver diseases from progressing towards cancer, whether or not they are related to a virus. » This is particularly promising at a time when the incidence of non-alcoholic steatohepatitis is rocketing in Western countries.

With his laboratory, the researcher has developed an initial candidate drug, a monoclonal antibody targeting CLDN1, whose initial preclinical assessments have just been completed. For this, the laboratory has developed spheroids, « mini-organs faithful to the liver’s three-dimensional cell architecture, which make it possible to better predict the clinical efficacy of candidate drugs. » The laboratory also has a bioinformatics platform for the integration of all results from ex vivo or in vivo experiments, from which computational analysis can identify molecular pathways or targets of interest.

Baumert has also created a start-up developing other monoclonal antibodies for the treatment of fibrosis and liver cancer. « This new ERC funding represents genuine recognition for my team’s work so far and should enable us to bring our project to fruition. »

*Unit 1110 Inserm/Université de Strasbourg, Institute of Viral and Liver Disease (Strasbourg).
** Targeted strategies for prevention and treatment of fibrosis-associated liver cancer – FIBCAN