P28 PD Dr. Strnad
Iron and α1-antitrypsin accumulation as hepatocellular initiators of liver fibrosis

We aim to analyze the role of iron overload and α1-antitrypsin (AAT) mutation as human-relevant models of liver fibrosis initiation. The impact of lysosomal dysfunction will be assessed in hepcidin knockout (KOs, iron overload model) and AAT mutated animals cross-bred with p62 KO or CHOP KO mice. Animal studies will be complemented by evaluation of AAT patients in order to define mechanisms of disease development and the role of co-founding factors such as obesity and alcohol consumption. [...]

Publications

• Kuscuoglu D. , Bewersdorf L., Wenzel K., Gross A., Kobazi Ensari G., Luo Y., Kilic K., Hittatiya K., Golob-Schwarzl N., Leube R. W., Preisinger C., George J., Metwally M., Eslam M., Lampertico P., Petta S., Mangia A., Berg T., Boonstra A., Brouwer W. P., Abate M. L., Loglio A., Sutton A., Nahon P., Schaefer B., Zoller H., Aigner E., Trautwein C., Haybaeck J., Strnad P. (2021): Dual proteotoxic stress accelerates liver injury via activation of p62-Nrf2. Journal of Pathology, 254(1), 80-91, [5.979]
• Fromme M. , Schneider C. V., Pereira V., Hamesch K., Pons M., Reichert M. C., Benini F., Ellis P., Thorhauge K. T., Mandorfer M., Burbaum B., Woditsch V., Chorostowska-Wynimko J., Verbeek J., Nevens F., Genesca J., Miravitlles M., Nuñez A., Schaefer B., Zoller H., Janciauskiene S., Abreu N., Jasmins L., Gaspar R., Liberal R., Macedo G., Mahadeva R., Gomes C., Schneider K. M., Trauner M., Krag A., Gooptu B., Thorburn D., Marshall A., Hurst J. R., Lomas D. A., Lammert F., Gaisa N. T., Clark V., Griffiths W., Trautwein C., Turner A. M., McElvaney N. G., Strnad P. (2021): Hepatobiliary phenotypes of adults with alpha-1 antitrypsin deficiency. GUT 2021, gutjnl-2020-323729, [19.819]
• Heinrichs D. , Brandt E. F., Fischer P., Köhncke J., Wirtz T. H., Guldiken N., Djudjaj S., Boor P., Kroy D., Weiskirchen R., Bucala R., Wasmuth H. E., Strnad P., Trautwein C., Bernhagen J., Berres M.-L. (2021): Unexpected Pro-Fibrotic Effect of MIF in Non-Alcoholic Steatohepatitis Is Linked to a Shift in NKT Cell Populations. Cells, in press, [5.656]
• Atkinson S. , R., Grove J. I., Liebig S., Astbury S., Vergis N., Goldin R., Quaglia A., Bantel H., Guha I. N., Thursz M. R., Newcombe P., Strnad P., Aithal G. P. (2020): In Severe Alcoholic Hepatitis, Serum Keratin-18 Fragments Are Diagnostic, Prognostic and Theragnostic Biomarkers. American Journal of Gastroenterology, 115(11), 1857-1868, [10.171]
• Schneider C.V. , Hamesch K., Gross A., Mandorfer M., Moeller L. S., Pereira V., Pons M., Kuca P., Reichert M. C., Benini F., Burbaum B., Voss J., Gutberlet M., Woditsch V., Lindhauer C., Fromme M., Kümpers J., Bewersdorf L., Schaefer B., Eslam M., Bals R., Janciauskiene S., Carvão J., Neureiter D., Zhou B., Wöran K., Bantel H., Geier A., Dirrichs T., Stickel F., Teumer A., Verbeek J., Nevens F., Govaere O., Krawczyk M., Roskams T., Haybaeck J., Lurje G., Chorostowska-Wynimko J., Genesca J., Reiberger T., Lammert F., Krag A., George J., Anstee Q. M., Trauner M., Datz C., Gaisa N. T., Denk H., Trautwein C., Aigner E., Strnad P. (2020): Liver Phenotypes of European Adults Heterozygous or Homozygous for Pi∗Z Variant of AAT (Pi∗MZ vs Pi∗ZZ genotype) and Noncarriers. Gastroenterology, 159, 534-548,
• Tangudu N. K. , Buth N., Strnad P., Cirstea I. C., Spasić M.V. (2019): Deregulation of Hepatic Mek1/2⁻Erk1/2 Signaling Module in Iron Overload Conditions. Pharmaceuticals (Basel), 12, E70, [3.800]
• Strnad P. , Buch S., Hamesch K., Fischer J., Rosendahl J., Schmelz R., Brueckner S., Brosch M., Heimes C. V., Woditsch V., Scholten D., Nischalke H. D., Janciauskiene S., Mandorfer M., Trauner M., Way M. J., McQuillin A., Reichert M. C., Krawczyk M., Casper M., Lammert F., Braun F., von Schönfels W., Hinz S., Burmeister G., Hellerbrand C., Teufel A., Feldman A., Schattenberg J. M., Bantel H., Pathil A., Demir M., Kluwe J., Boettler T., Ridinger M., Wodarz N., Soyka M., Rietschel M., Kiefer F., Weber T., Marhenke S., Vogel A., Hinrichsen H., Canbay A., Schlattjan M., Sosnowsky K., Sarrazin C., von Felden J., Geier A., Deltenre P., Sipos B., Schafmayer C., Nothnagel M., Aigner E., Datz C., Stickel F., Morgan M. Y., Hampe J., Berg T., Trautwein C. (2019): Heterozygous carriage of the alpha1-antitrypsin Pi*Z variant increases the risk to develop liver cirrhosis. Gut, 68, 1099-1107, [17.160]
• Spivak I. , Arora J., Meinzer C., Durkalski-Mauldin V., Lee W. M., Trautwein C., Fontana R. J., Strnad P. (2019): Low Serum Hepicidin is associated with reuced short-term survival in adults with acute liver failure. Hepatology, 59(5), 2136-2149, [14.079]
• Hamesch K. , Mandorfer M., Pereira V. M., Moeller L. S., Pons M., Dolman G. E., Reichert M. C., Heimes C. V., Woditsch V., Voss J., Lindhauer C., Fromme M., Spivak I., Guldiken N., Zhou B., Arslanow A., Schaefer B., Zoller H., Aigner E., Reiberger T., Wetzel M., Siegmund B., Simões C., Gaspar R., Maia L., Costa D., Bento-Miranda M., van Helden J., Yagmur E., Bzdok D., Stolk J., Gleiber W., Knipel V., Windisch W., Mahadeva R., Bals R., Koczulla R., Barrecheguren M., Miravitlles M., Janciauskiene S., Stickel F., Lammert F., Liberal R., Genesca J., Griffiths W. J., Trauner M., Krag A., Trautwein C., Strnad P., European Alpha1-Liver Study Group (2019): Liver Fibrosis and Metabolic Alterations in Adults with Alpha1 Antitrypsin Deficiency Caused by the Pi*ZZ Mutation. Gastroenterology, 157, 705-719, [20.773]
• Guldiken N. , Hamesch K., Schuller S. M., Aly M., Lindhauer C., Schneider C. V., Fromme M., Trautwein C., Strnad P. (2019): Mild Iron Overload is not a major driver of liver fibrogenesis in individuals homozygous for the Alpha-1 Antitrypsin Pi*Z Variant. Cells, 8(11), 1415, [5.656]
• Levada K. , Guldiken N., Zhang X., Vella G., Mo F., James L. P., Haybaeck J., Kessler S. M., Kiemer A. K., Ott T., Hartmann D., Hüser N., Ziol M., Trautwein C., Strnad P. (2018): Hsp72 protects from liver injury via attenuation of hepatocellular death, oxidative stress and JNK-signaling. J Hepatol, 68, 996-1005, [18.946]
• Gross A. , Pack L. A. P., Schacht G. M., Kant S., Ungewiss S., Meir M., Schlegel N., Preisinger C., Boor P., Güldiken N., Krusche C. A., Sellge G., Trautwein C., Waschke J., Heuser A., Leube R. E., Strnad P. (2018): Desmoglein 2, but not desmocollin 2, protects intestinal epithelia from injury. Mucosal Immunol, 11, 1630-1639, [7.352]
• Alsamman, M. , Sterzer, V., Meurer, S. K., Sahin, H., Schaeper, U., Kuscuoglu, D., Strnad, P., Weiskirchen, R., Trautwein, C., Scholten, D. (2018): Endoglin in human liver disease and murine models of liver fibrosis – a protective factor against liver fibrosis. Liver International, 38, 858-867, [4.470]
• Strnad, P. , Tacke, F., Koch, A., Trautwein (2017): Liver - guardian, modifier and target of sepsis. Nature Reviews Gastroenterology & Hepatology, 14(1), 55-66, [14.435]
• Bruns, T. , Nuraldeen, R., Mai, M., Stengel, S., Zimmermann, H., Yagmur, E., Trautwein, C., Stallmach, A., Strnad, P. (2017): Low serum transferrin correlates with acute-on-chronic organ failure and indicates short-term mortality in decompensated cirrhosis. Wiley Liver International, 37 (2), 232–241, [4.470]
• Lunova, M. , Schwarz, P., Nuraldeen, R., Levada, K., Kuscuoglu, D., Stützle, M., Vuji´c Spasi´c, M., Haybaeck, J., Ruchala, P., Jirsa, M., Deschemin, J.-C., Vaulont, S., Trautwein, C., Strnad, P. (2017): Hepcidin knockout mice spontaneously develop chronic pancreatitis owing to cytoplasmic iron overload in acinar cells. Journal of Pathology, 241(1), 104–114, [7.381]
• Guldiken N. , Ensari G.K., Lahiri P., Couchy G., Preisinger C., Liedtke C., Zimmermann H.W., Ziol M., Boor P., Zucman-Rossi J., Trautwein C., Strnad P. (2016): Keratin 23 is a general stress-inducible marker of mouse and human ductular reaction in liver disease. Journal of Hepatology, 65(3), 552–559, [10.590]
• Djudjaj S. , Papasotiriou M., Bülow R.D., Wagnerova A., Lindenmeyer M.T., Cohen C.D., Bucala R., Strnad P., Goumenos D.S., Floege J., Boor P. (2016): Keratins as Novel Markers of Renal Epithelial Cell Injury. Kidney International, 89 (4), 792-808, [7.683]
• Usachov, V. , Urban, T. J., Fontana, R. J., Gross, A., Iyer, S., Omary, M. B., Strnad, P. (2015): Prevalence of genetic variants of keratins 8 and 18 in patients with drug-induced liver injury.. BMC Medicine, 13, 196, [2.726]
• Wallace, M. C., , Hamesch, K., Lunova, M., Kim, Y., Weiskirchen, R., Strnad, P., Friedman, S. L. (2015): Standard Operating Procedures in experimental liver research: Thioacetamide model in mice. Laboratory Animals, 49(1), 59-69, [1.120]
• Szabo, S. , Wögenstein, K. L., Österreicher, C. H., Guldiken, N., Chen, Y., Doler, C., Wiche, G., Haybaeck, J., Strnad, P., Fuchs, P. (2015): Epiplakin attenuates experimental mouse liver injury by chaperoning keratin reorganization.. J Hepatol, 62, 1357-1366, [11.340]
• Toivola, D. M. , Boor, P., Alam, C., Strnad, P. (2015): Keratins in health and disease.. Current Opinion in Cell Biology, 32, 73-81, [8.851]
• Sunami, Y. , Von Figura, G., Kleger, A., Strnad, P., Hüser, N., Hartmann, D. (2015): The Role of Telomeres in Liver Disease. Prog Mol Biol Transl Sci, 125, 159-172,
• Lunova, M. , Trautwein, C., Nahon, P., Strnad, P. (2015): Hepcidin in chronic liver disease and hepatocellular carcinoma: The plot thickens. J Hepatol, 62, 979-980, [10.590]
• Hamesch, K. , Borkham-Kamphorst, E., Strnad, P., Weiskirchen, R. (2015): Lipopolysaccharide-induced inflammatory liver injury in mice.. Lab Anim, 49(S1), 37-46, [1.120]
• Guldiken, N. , Zhou, Q., Kucukoglu, O., Rehm, M., Levada, K., Gross, A., Kwan, R., James, L. P., Trautwein, C., Omary, M. B., Strnad, P. (2015): Human keratin 8 variants promote mouse acetaminophen hepatotoxicity coupled with JNK activation and protein adduct formation.. Hepatology, , in press, [11.050]
• Guldiken, N. , Usachov, V., Levada, K., Trautwein, C., Ziol, M., Nahon, P., Strnad, P. (2015): Keratins 8 and 18 are type II acute-phase responsive genes overexpressed in human liver disease.. Liver Int, 35, 1203-1212, [4.850]
• Wögenstein, K. L. , Szabo, S., Lunova, M., Wiche, G., Haybaeck, J., Strnad, P., Boor, P., Wagner, M., Fuchs, P. (2014): Epiplakin-deficiecy aggravates caerulein-induced murine pancreatitis by impaired acinar keratin filament reorganization. PLoS One, 18 (9), e108323, [3.057]
• Strnad, P. , Nuraldeen, R., Guldiken, N., Hartmann, D., Mahajan, V., Denk, H., Haybaeck, J. (2014): Broad Spectrum of Hepatocyte Inclusions in Humans, Animals, and Experimental Models. Comprehensive Physiology, 3 (4), 1393-1436, [6.364]
• Lunova, M. , Goehring, C., Mueller, K., Chen, Y., Walther, P., Vaulont, S., Haybaeck, J., Lackner, C., Trautwein, C., Strnad, P. (2014): Hepcidin knockout mice fed with iron-rich diet develop chronic liver injury and liver fibrosis due to lysosomal iron overload.. Journal of Hepatology, 61 (3), 633-641, [10.590]
• Kucukoglu, O. , Guldiken, N., Chen, Y., Usachov, V., Elheliebi, A., Haybaeck, J., Denk, H. W., Trautwein, C., Strnad, P. (2014): High-fat diet triggers Mallory-Denk body formation via misfolding and crosslinking of excess keratin 8.. Hepatology, 60 (1), 169-178, [11.711]
• Strnad, P. , Von Figura, G., Gruss, R., Jareis, K. M., Stiehl, A., Kulaksiz, H. (2013): Oblique Bile Duct Predisposes to the Recurrence of Bile Duct Stones. Plos One, 8(1), [3.057]
• Mueller, K. , Sunami, Y., Stuetzle, M., Güldiken, N., Kucukoglu, O., Mueller, S., Kulaksiz, H. W., Schwarz, P., Strnad, P. (2013): CHOP-mediated hepcidin suppression modulates hepatic iron load. The Journal of Pathology, 231 (4), 532-542, [7.381]