The Institute of Viral and Liver disease 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, this program will impact the management of patients with liver disease and cancer in France, Europe and beyond.

I- Unraveling the cell circuits of liver disease and cancer to discover novel therapeutic targets

Principal Investigator: Prof. Thomas F. Baumert, MD, PhD

Chronic liver disease and cancer are key challenges of public health with unsatisfactory treatment options. Key causes are chronic viral infection and metabolic disease (NASH). My laboratory focuses on unraveling the cell circuits of liver disease and cancer to discover novel therapeutic targets. Using a recently established single cell RNASeq pipeline (Aizarani, Saviano et al. Nature 2019) combined with advanced proteomics and patient-derived cell culture and animal models (Mailly et al. Nature Biotech 2015) my laboratory aims to understand the cell circuits of virus- and metabolic liver cancer (Hamdane et al. Gastroenterology 2019, Lupberger et al. Gastroenterology 2019). Furthermore, my team is exploring host cell targets to eliminate hepatitis B virus infection – a major cause of liver cancer world-wide. The understanding of disease biology on a molecular level enables us to uncover novel targets and compounds for treatment. A unique hallmark of my 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 concepts and compounds into the clinic.

Associated Investigators :

Dr. François Duong, PhD

Dr. Atish Mukherji, PhD

II- Molecular biology of HCV virus-host interactions

Principal Investigator: Dr. Catherine Schuster, PhD

Aiming at the identification of novel targets for preventive and therapeutic strategies against Hepatitis C virus (HCV)-induced liver disease, we focus on the characterization of virus host-interactions and the pathogenesis of HCV infection during the late steps of the HCV life cycle. We are especially interested in the relationship between HCV and cell host lipids and lipoproteins as well as the regulation of HCV IRES driven translation.

III- Signaling and virus-host interactions 

Principal Investigator: Dr. Joachim Lupberger, PhD

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 pattern 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.

IV- Molecular biology of HBV and HDV virus-host interactions

Principal Investigator: Dr. Eloi Verrier, PhD

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.

V- SARS-CoV-2 coronavirus-host interactions and therapeutic targets

Principal Investigator: Prof. Thomas F. Baumert, MD, PhD

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 currently almost 130.000 people infected and close to 5000 deceased from the Covid-19 disease the search for factors involved in virus spread and replication is paramount to develop tools to fight the ongoing pandemic.

Using our internationally recognized expertise to discover host factors as targets for antiviral therapy (Lupberger et al, Nat Med 2011; Zona et al, Cell Host Microbe 2013; Mailly, Nat Biotechnol 2015; Verrier et al, Hepatology 2016; Colpitts et al, Gut 2018, Verrier ER, Gut 2020; reviewed in Crouchet et al, Therap Adv Gastroenterol 2018) we have established the expertise and model systems to contribute to the global effort to find novel compounds to fight SARS-CoV-2 infection. Using established coronavirus model systems (Letko et al, Nat Microbiol 2020, Hoffmann et al, Cell 2020) we will 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.