Dazert Eva, Colombi Marco, Boldanova Tujana, Moes Suzette, Adametz David, Quagliata Luca, Roth Volker, Terracciano Luigi, Heim Markus H, Jenoe Paul, Hall Michael N (2016), Quantitative proteomics and phosphoproteomics on serial tumor biopsies from a sorafenib-treated HCC patient., in Proceedings of the National Academy of Sciences of the United States of America
, 113(5), 1381-6.
Marti Patricia, Stein Claudia, Blumer Tanja, Abraham Yann, Dill Michael T, Pikiolek Monika, Orsini Vanessa, Jurisic Giorgia, Megel Philippe, Makowska Zuzanna, Agarinis Claudia, Tornillo Luigi, Bouwmeester Tewis, Ruffner Heinz, Bauer Andreas, Parker Christian N, Schmelzle Tobias, Terracciano Luigi M, Heim Markus H, Tchorz Jan S (2015), YAP promotes proliferation, chemoresistance, and angiogenesis in human cholangiocarcinoma through TEAD transcription factors., in Hepatology (Baltimore, Md.)
, 62(5), 1497-510.
Duong Francois H T, Trincucci Gaia, Boldanova Tujana, Calabrese Diego, Campana Benedetta, Krol Ilona, Durand Sarah C, Heydmann Laura, Zeisel Mirjam B, Baumert Thomas F, Heim Markus H (2014), IFN-λ receptor 1 expression is induced in chronic hepatitis C and correlates with the IFN-λ3 genotype and with nonresponsiveness to IFN-α therapies., in The Journal of experimental medicine
, 211(5), 857-68.
Heim Markus H, Thimme Robert (2014), Innate and adaptive immune responses in HCV infections., in Journal of hepatology
, 61(1 Suppl), 14-25.
Dill Michael T, Makowska Zuzanna, Trincucci Gaia, Gruber Andreas J, Vogt Julia E, Filipowicz Magdalena, Calabrese Diego, Krol Ilona, Lau Daryl T, Terracciano Luigi, van Nimwegen Erik, Roth Volker, Heim Markus H (2014), Pegylated IFN-α regulates hepatic gene expression through transient Jak/STAT activation., in The Journal of clinical investigation
, 124(4), 1568-81.
Duong François H T, Dill Michael T, Matter Matthias S, Makowska Zuzanna, Calabrese Diego, Dietsche Tanja, Ketterer Sylvia, Terracciano Luigi, Heim Markus H (2014), Protein phosphatase 2A promotes hepatocellular carcinogenesis in the diethylnitrosamine mouse model through inhibition of p53., in Carcinogenesis
, 35(1), 114-22.
Terczyńska-Dyla Ewa, Bibert Stephanie, Duong Francois H T, Krol Ilona, Jørgensen Sanne, Collinet Emilie, Kutalik Zoltán, Aubert Vincent, Cerny Andreas, Kaiser Laurent, Malinverni Raffaele, Mangia Alessandra, Moradpour Darius, Müllhaupt Beat, Negro Francesco, Santoro Rosanna, Semela David, Semmo Nasser, Heim Markus H, Bochud Pierre-Yves, Hartmann Rune (2014), Reduced IFNλ4 activity is associated with improved HCV clearance and reduced expression of interferon-stimulated genes., in Nature communications
, 5, 5699-5699.
Wieland Stefan, Makowska Zuzanna, Campana Benedetta, Calabrese Diego, Dill Michael T, Chung Josan, Chisari Francis V, Heim Markus H (2014), Simultaneous detection of hepatitis C virus and interferon stimulated gene expression in infected human liver., in Hepatology (Baltimore, Md.)
, 59(6), 2121-30.
Balmer Maria L, Slack Emma, de Gottardi Andrea, Lawson Melissa A E, Hapfelmeier Siegfried, Miele Luca, Grieco Antonio, Van Vlierberghe Hans, Fahrner René, Patuto Nicola, Bernsmeier Christine, Ronchi Francesca, Wyss Madeleine, Stroka Deborah, Dickgreber Nina, Heim Markus H, McCoy Kathy D, Macpherson Andrew J (2014), The liver may act as a firewall mediating mutualism between the host and its gut commensal microbiota., in Science translational medicine
, 6(237), 237-66.
Lange Christian M, Gouttenoire Jérôme, Duong François H T, Morikawa Kenichi, Heim Markus H, Moradpour Darius (2014), Vitamin D receptor and Jak-STAT signaling crosstalk results in calcitriol-mediated increase of hepatocellular response to IFN-α., in Journal of immunology (Baltimore, Md. : 1950)
, 192(12), 6037-44.
Heim Markus (2013), 25 years of interferon-based treatment of chronic hepatitis C: an epoch coming to an end., in Nature Reviews Immunology
Heim Markus (2013), Innate immunity and HCV., in Journal of Hepatology
Duong François H T, Dill Michael T, Matter Matthias S, Makowska Zuzanna, Calabrese Diego, Dietsche Tanja, Ketterer Sylvia, Terracciano Luigi, Heim Markus H (2013), Protein phosphatase 2A promotes hepatocellular carcinogenesis in the diethylnitrosamine mouse model through inhibition of p53., in Carcinogenesis
, 35(1), 114-22.
Makowska Zuzanna, Blumer Tanja, Duong François H T, La Monica Nicola, Kandimalla Ekambar R, Heim Markus H (2013), Sequential induction of type I and II interferons mediates a long-lasting gene induction in the liver in response to a novel toll-like receptor 9 agonist., in Journal of hepatology
, 58(4), 743-9.
Chronic hepatitis C (CHC) is a major cause of chronic liver disease. An important and striking feature of hepatitis C virus (HCV) is its tendency toward chronicity. In > 70% of infected individuals, HCV establishes a persistent infection over decades that may lead to cirrhosis and hepatocellular carcinoma. This high rate of persistence is linked to an ability of HCV to evade and antagonize the immune response of the host. Type I interferons (IFNs) are crucial and potent components of the early host response against virus infection and recombinant pegylated IFNa (pegIFNa) in combination with ribavirin is the current standard therapy for CHC. About half of the patients can be cured.In the current BoE application, we plan to address several key points of the innate immune response to hepatitis C virus infection.1. Analysis of liver biopsies of HCV infected patients with a newly developed fluorescence in situ hybridization method (FISH).We will use a newly developed FISH method to visualize and quantify HCV RNA and mRNAs of IFNs and IFN stimulated genes in liver biopsies.2. IFNa induced signaling in the human liver.The pharmacodynamic effects of pegylated IFNa will be studied in liver biopsies obtained at different time points during the week after the first injection of pegylated IFNa in patients with CHC .3. The role of IFN? in establishing and maintaining IFN stimulated gene expression in the liver of HCV infected patients.We plan to systematically study IFN? and IFN? receptor expression in liver biopsies of patients with chronic hepatitis C (and controls) and correlate the status of the IFN? system with hepatic IFN stimulated gene expression. We will investigate the molecular mechanisms that links IL28B genotype with IFN stimulated gene expression and with non-response to pegIFN-a/ribavirin combination therapies.4. Functional characterization of IFNa induced long non-coding RNAs (lncRNAs)We have identified hundreds of lncRNAs that are induced by IFNa. We plan to study if some of them have a role in negative regulation of genes by IFNa.