Research
The key focus of our research is to understand the disease biology and the discovery of novel strategies to prevent and treat liver cancer caused by viruses or metabolic disease. Liver fibrosis progressing to cancer is a significant public health burden with rising prevalence, with 5.3 million patients in the EU alone. The aging population combined with lifestyle changes, obesity, and diabetes result in a rapidly increasing number of patients with hepatobiliary cancer world-wide. Around one million patients die each year from liver cancer.
Treatment options for liver diseases and cancer are unsatisfactory. Currently approved therapies to treat metabolic liver disease are still unsatisfactory by limited efficacy for fibrosis, the main risk factor for liver cancer. When fibrosis progresses to cancer, only a minority of patients are eligible for curative approaches, Current therapies for advanced hepatocellular or cholangiocarcinoma remain unsatisfactory by limited response and significant adverse effects. While hepatitis C virus infection is curable, chronic hepatitis B and D infection can be efficiently treated by antivirals but cure is rare and the risk to develop liver cancer remains.
Prevention of chronic liver disease and cancer requires cure of chronic viral infection. Another challenge for prevention of liver cancer is the absence of antivirals effectively curing chronic HBV and HDV infection. A better comprehension of the molecular mechanisms governing HBV/HDV-host interactions is needed to develop novel strategies for HBV/HDV cure beyond the state-of-the-art.
There is an unmet need for non-invasive biomarkers robustly predicting liver disease progression and HCC risk. Quantification of liver disease and fibrosis by liver biopsy is still the gold standard. However, this procedure presents a significant risk for the patients and is not suitable for detailed longitudinal studies. While there has been marked progress in surrogate biomarkers assessing the degree liver fibrosis including non-invasive biomarkers such as the ELF score, MRI imaging or the prognostic liver signature (PLS), next generation non-invasive biomarkers to identify patients with advanced fibrosis at risk for decompensation or development of HCC are needed.
Discovery of novel therapeutic approaches and biomarkers will require novel patient-derived liver disease model systems. Since many compounds in clinical development target specifically human biology (such as monoclonal antibodies or immune-based approaches), patient-derived models expressing the human target are needed for fast-track development.
Our aim is to make impactful discoveries that will change patient lives.
Prof. Thomas Baumert
Our Research Program
The flagship of our unit is an innovative, integrative liver disease research program addressing the next challenges in liver disease by unraveling novel therapeutic targets and biomarkers. Our research is organized around several complementary axes:
Unravelling the cell circuits driving liver disease progression and cancer as therapeutic targets
Combining single cell RNASeq, spatial transcriptomics, epigenetics and proteomics pipelines investigating patient tissues and applying patient-derived cell culture and animal models, our work aims to unravel the cell circuits of liver disease and cancer to discover novel therapeutic targets. A unique hallmark of this program is the integration of experimental perturbation studies with patient data using advanced computational bioinformatic analyses, machine learning and artificial intelligence.
Uncovering virus-host interactions to discover novel targets for cure of chronic hepatitis B and D viruses
Focusing on virus-host interactions of hepatitis B and D virus (HBV and HDV) infections, our key goal is to understand the viral life cycle of HBV and HDV and uncover hepatocyte host factors mediating HBV and HDV infection. In collaboration with national and international leading research groups, we are applying novel model systems and cutting-edge functional genomics for drug and target discovery. New therapeutic agents targeting these candidate host factors constitute a major step towards the development of novel treatments for viral cure.
Developing cutting-edge patient-derived models for liver disease and cancer
We are developing next generation patient-derived systems to model fibrosis and cancer in patients and gain a better understanding of the disease biology. Such systems enable us to identify and characterize novel therapeutic approaches, and accelerate their clinical translation.
Translating discoveries into novel clinical therapeutic strategies in the patient
Bridging basic and translational research with clinical and medical excellence and industrial partnerships, we promote the discovery of new diagnostic tools and therapeutics to improve the clinical outcome of patients. The program includes the application of research findings from cellular models, patient tissues, and small animal models, to clinical research in patient cohorts. We aim to validate the functional relevance of the uncovered mechanisms by proof-of-concept studies in vivo and in patient cohorts, accelerating the rapid translation of our discoveries to clinical practice.
Understand the role of Claudin-1 for fibrosis and cancer as a novel therapeutic target
One example of our translational work is the discovery of Claudin-1 as a therapeutic target for liver fibrosis and cancer. We discovered and characterized highly potent and safe monoclonal antibodies which are now in clinical trials led by our spin-off Alentis Therapeutics. Based on this translational work and our unique monoclonal antibodies, therapeutic tools and models in the field of Claudin-1 disease biology, we aim to understand the role of Claudin-1 as a therapeutic target in fibrosis and cancer across organs including the development of next generation therapeutics and modalities targeting Claudin-1 and other members of the Claudin family.
Relevance of patient care pathways and the ecological transition in healthcare
The sustainability of a modern healthcare system relies on three pillars: it’s economical efficiency, it’s social equity, and it’s environmental sustainability. This work group focuses on integrating care practices and on establishing evaluation frameworks that take all of these criteria into account in patient management and throughout the patient pathway. For that purpose, the development of tools adapted to monitoring and transmitting information is necessary. Leveraging new technologies and artificial intelligence can enable us to reach 4P.0 medicine: preventive, predictive, participative and personalized. The inclusion of novel environmental indicators is necessary for the health sector to reduce it’s environmental impact, while guaranteeing high quality care. This research axis explores the evolution of care practices and the integration to a ecological dimension. These objectives are in line with those of the Cet axe de recherche explore l’évolution de l’évaluation des soins, et l’intégration d’une dimension écologique. Ces objectifs sont en phase avec ceux du Collective for Eco-Responsibility in Health (CERES), presided par Prof. Pessaux.
Our Research Platforms
Our institute boasts several state-of-the-art facilities including a BSL3 facility, animal models facilities and high-throughput model systems suitable for target and/or therapeutic drug discovery for viral infections and liver disease. We can provide access to the scientific community through collaborations or fee-for-service agreements. The high standard of our facilities and services has been repeatedly called upon by industry and world-class research leaders and we have several ongoing programs with external partners.
Patient-Derived Platform
Our unique state-of-the-art patient-derived liver spheroid platform generates and supplies cutting-edge patient-derived models for high quality translational research research for liver and biliary fibrosis as well as liver and gastrointestinal cancers. These models are handled by a highly qualified licensed staff. Infrastructure and approaches are available to the scientific community within collaborations or fee-for-service agreements.
Translational Medicine / Bioinformatics
We model cell circuits in human disease biology. Our expertise comprises the integration of cell, animal and patient data contributing to unravel novel therapeutic concepts and targets, single- cell transcriptomics and proteomics, as well as data analyses from epigenetic (ChIP-seq), mutational (DNA-seq), and transcriptomic (RNA-seq) next-generation sequencing. We study functional gene pathway enrichment analysis and contribute to drug screen assessment using genome-wide and signature approaches (such as NanoString® technology). We apply machine learning and artificial intelligence to uncover novel pathways for disease biology and therapeutic targets.
BSL3 Platform
Our BSL3 laboratory offers a safe and contained environment for the production and manipulation of viruses such as HCV, HBV, HIV, SARS-CoV-2. It contains six class II biological safety cabinets, a Biomek NXP automated workstation for high-throughput manipulation and a Mithras LB 940 Multimode Microplate Reader from Berthold (equipped for luminescence, BRET, FRET, fluorescence and colorimetry) as well as, a SONY cell sorter. We offer our services to external users interested in using our technology and that would like to benefit from our expertise.
Patient-derived Animal Models / A3 Platform - AEPIC
Our unique state-of-the-art animal facility includes an A3 zone and a specific pathogen-free area to ensure that research programs involving small animal models can be performed to the highest standard of animal care welfare and scientific quality. We are developing cutting-edge models in liver disease and viral infection. A hallmark of the platform are patient-derived animal models including human liver chimeric mouse models and patient-derived xenograft models. These models are developed and maintained by highly qualified licensed staff. Infrastructure and approaches are available to the scientific community within collaborations or fee-for-service agreements.
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