The Institute of Viral and Liver Diseases develops innovative integrative research programs addressing the next challenges in liver disease by unraveling novel therapeutic targets and biomarkers. By providing a novel understanding of liver disease biology and the discovery of novel targets and biomarkers, these programs will impact the management of patients with liver disease and cancer in France, Europe and beyond.
Personalized medicine approaches for the discovery of novel therapeutic targets and biomarkers for advanced liver disease and liver cancer
Chronic liver disease and cancer are key challenges of public health with unsatisfactory treatment options. Key causes are non-alcoholic fatty liver disease (NASH) and chronic viral infection. Using a recently established single cell RNASeq pipeline (Aizarani et al. Nature 2019) combined with advanced proteomics and patient-derived cell culture and animal models (Mailly et al. Nature Biotech 2015), my group aims to understand the cell circuits of virus-induced and metabolic liver cancer (Hamdane et al. Gastroenterology 2019, Lupberger et al. Gastroenterology 2019). The understanding of disease biology on a molecular level enables us to uncover novel targets and compounds for treatment. A unique hallmark of our program is the integration of laboratory studies with patient data using advanced computational analyses. In collaboration with Biotech, Pharma and the IHU and Strasbourg University Hospitals we translate our findings and compounds into the clinic.
HBV / HDV
Molecular biology of HBV and HDV virus-host interactions
Our laboratory focuses on virus-host interactions in the context of hepatitis B and D virus (HBV and HDV) infections, the most aggressive forms of chronic viral hepatitis and leading causes of hepatocellular carcinoma worldwide. To date, no treatment allows viral cure. Our key focus is to understand the viral life cycle of HDV and uncover hepatocyte host factors mediating HDV infection as novel therapeutic targets for cure. 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. The discovery of new therapeutic agents targeting these candidate host factors constitutes a major step towards the development of novel treatments for viral cure.
HCV / SIGNALING
Signaling and virus-host interactions
To uncover the signaling pathways and drivers of liver disease progression we are assessing the phospho-proteomic landscape of liver disease models. We are using cutting edge bioinformatics to identify etiology-specific and common signaling patterns and to predict regulatory circuits and drivers of liver disease progression as putative targets for chemopreventive strategies. We validate the identified pathways using liver disease animal models and conduct small molecule drug screenings targeting identified signaling pathways with potential relevance for hepatocellular carcinoma development.
SARS-CoV-2 coronavirus-host interactions and therapeutic targets
The novel Coronavirus SARS-CoV-2 that emerged in China in December 2019 and is continuing to spread all over the world constitutes a major public health emergency with 133 M cases and over 550 k related deaths worldwide and rising.
Using our internationally recognized expertise to discover host factors as targets for antiviral therapy, we have established the expertise and model systems to contribute to the global effort to find novel compounds to fight SARS-CoV-2 infection. We aim to discover host factors for the coronavirus life cycle focusing on virus cell entry and replication. Specifically, we will assess the antiviral activity of compounds targeting common host factors of HCV and coronaviruses. Collectively, we anticipate that our program will uncover novel strategies and compounds for antiviral therapy for urgently needed control and cure of coronavirus infection.
Bridging basic and translational research with clinical and medical excellence and industrial partnership, the overall objective of this program is to promote the discovery of new diagnostic tools and treatments to improve the clinical outcome of patients affected by advanced liver diseases. The program, directed by Dr. Schuster, includes the application of research findings from cells, tissues, and animals, to clinical research in patient populations. By taking advantage of our established small animal model systems and unique patient cohorts, this program will validate the functional relevance of the uncovered mechanisms by proof-of-concept studies in vivo and in patient cohorts, accelerating the rapid translation our discoveries to clinical practice.
Measuring and comparing means better knowing and understanding current practices, learning from others, and continually questioning yourself. The “value based health care” (VBHC) is a model which proposing to compare results that are important to patients (clinical results or CROMs, patient experience results or PREMs, quality results of life reported by the patient or PROMs) and costs necessary to achieve these results.
The objective of our research group is to set up standardized questionnaires for the patient care, and to compare them with a medico-economic assessment. This voluntary approach lays the foundations and conditions for creating a virtuous circle of improving practices. All patients from the Hepato-Digestive Pole of the NHC in Strasbourg will be included in these analyses. The next step is to set-up multicenter studies to disseminate the obtained results within the French medical community.
The objective is also to create an innovative organizational support that will be evaluated by the same approach.
Finally, these new approaches will require the development of suitable tools for monitoring and transmitting information. Continuous assessment using real-life data would help introduce more agility between innovations and their application. New technologies including digitization and the contribution of Artificial Intelligence make it possible to envisage an evolution of medicine towards a Medicine known as 4.0 or rather 4P.0: Preventive, Predictive, Participatory and Personalized. The analysis of large sets of collective data will allow each patient, disease, and therapy to be fully detailed, justified and individualized.
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.
Our BSL3 laboratory offers a safe and contained environment for the production and manipulation of viruses such as HCV, HBV, HIV and 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.
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).
LIVER DISEASE ANIMAL MODELS / A3 PLATFORM
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. 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.
Our unique state-of-the-art patient-derived liver spheroid platform generates and supplies cutting-edge patient-derived models for high quality translational research. 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.