Die Projekte meiner Arbeitsgruppe widmen sich der Erforschung der molekularen Pathogenese akuter und chronischer Lebererkrankungen und zielen auf die Entwicklung zukünftiger rationaler Therapieansätze. Hierbei stehen im Fokus unseres Interesses nukleäre Enzyme, die sowohl Alterungsprozesse als auch die zelluläre Differenzierung bzw. Entartung regulieren können. Auf molekularer Ebene wirken Sie als Sensoren für den energetischen Zustand von Zellen und koordinieren über epigenetische Genregulationsmechanismen die kontinuierliche Anpassung an unterschiedliche Stresssituationen. Wir untersuchen die Mechanismen, die bei gestörter Enzymaktivität eine fehlerhafte molekulare Anpassung hervorrufen und dadurch die Pathogenese chronisch entzündlicher Lebererkrankungen, Zirrhose und Leberkrebs fördern. Durch diese Untersuchungen sollen therapeutische Ziele definiert werden, die einen Ansatzpunkt für die Entwicklung neuer Medikamente bilden.

Castven D, Becker D, Czauderna C, Wilhelm D, Andersen JB, Strand S, Hartmann M, Heilmann-Heimbach S, Roth W, Hartmann N, Straub BK, Mahn FL, Franck S, Pereira S, Haupts A, Vogel A, Wörns MA, Weinmann A, Heinrich S, Lang H, Thorgeirsson SS, Galle PR, Marquardt JU. Application of patient-derived liver cancer cells for phenotypic characterization and therapeutic target identification. Int J Cancer. 2019 Jun 1;144(11):2782-2794. doi: 10.1002/ijc.32026.

Ahmed S, Strand S, Weinmann-Menke J, Urbansky L, Galle PR, Neumann H. Molecular Endoscopic Imaging in Cancer. Dig Endosc. 2018 May 30. doi: 10.1111/den.13199.

Kiweler N, Brill B, Wirth M, Breuksch I, Laguna T, Dietrich C, Strand S, Schneider G, Groner B, Butter F, Heinzel T, Brenner W, Krämer OH. The histone deacetylases HDAC1 and HDAC2 are required for the growth and survival of renal carcinoma cells. Arch Toxicol. 2018 Jul;92(7):2227-2243. doi: 10.1007/s00204-018-2229-5.

Czauderna C, Palestino-Dominguez M, Castven D, Becker D, Zanon-Rodriguez L, Hajduk J, Mahn FL, Herr M, Strand D, Strand S, Heilmann-Heimbach S, Gomez-Quiroz LE, Wörns MA, Galle PR, Marquardt JU Ginkgo biloba induces different gene expression signatures and oncogenic pathways in malignant and non-malignant cells of the liver. PLoS One. 2018 Dec 21;13(12):e0209067. doi: 10.1371/journal.pone.0209067.

Steinmetz C, Kashyap A, Zhivkova N, Alizor H, Ernst I, Gottfried-Brand D, Janssen H, Teufel A, Schulze-Bergkamen H, Lotz J, Kuball J, Theobald M, Heise M, Lang H, Galle PR, Strand D, Strand S. Activation of SIRT1 by human chorionic gonadotropin exerts a therapeutic effect on hepatic injury and inflammation. Hepatology. 2017 Jan 21. doi: 10.1002/hep.29072.

Wolf K, Strand S. Assessing the Histone Deacetylase Activity of SIRT6 in Primary Murine Hepatocytes via Proximity Ligation Assay. Methods Mol Biol. 2017;1510:149-158.

Sahu SK, Tiwari N, Pataskar A, Zhuang Y, Borisova M, Diken M, Strand S, Beli P, Tiwari VK.FBXO32 promotes microenvironment underlying epithelial-mesenchymal transition via CtBP1 during tumour metastasis and brain development. Nat Commun. 2017 Nov 15;8(1):1523. doi: 10.1038/s41467-017-01366-x.

Castven D, Fischer M, Becker D, Heinrich S, Andersen JB, Strand D, Sprinzl MF, Strand S, Czauderna C, Heilmann-Heimbach S, Roessler S, Weinmann A, Wörns MA, Thorgeirsson SS, Galle PR, Matter MS, Lang H, Marquardt JU.Adverse genomic alterations and stemness features are induced by field cancerization in the microenvironment of hepatocellular carcinomas. Oncotarget. 2017 Jul 25;8(30):48688-48700. doi: 10.18632/oncotarget.16231. 

Etzold A, Galetzka D, Weis E, Bartsch O, Haaf T, Spix C, Itzel T, Schweiger S, Strand D, Strand S*, Zechner U*. CAF-like state in primary skin fibroblasts with constitutional BRCA1 epimutation sheds new light on tumor suppressor deficiency-related changes in healthy tissue. Epigenetics. 2016;11(2):120-31. doi:10.1080/15592294.2016.1140295.

Fichter M, Piradashvili K, Pietrzak-Nguyen A, Pretsch L, Kuhn G, Strand S, Knuf M, Zepp F, Wurm FR, Mailänder V, Landfester K, Gehring S. Polymeric hepatitis C virus non-structural protein 5A nanocapsules induce intrahepatic antigen-specific immune responses.
Biomaterials. 2016 Nov;108:1-12. doi: 10.1016/j.biomaterials.2016.08.046. 

Itzel T, Scholz P, Maass T, Krupp M, Marquardt JU, Strand S, Becker D, Staib F, Binder H, Roessler S, Wang XW, Thorgeirsson S, Müller M, Galle PR, Teufel A. Translating bioinformatics in oncology: Guilt-by-profiling analysis and identification of KIF18B and CDCA3 as novel driver genes in carcinogenesis. Bioinformatics 2015; 31(2):216-24. doi: 10.1093/bioinformatics/btu586.

Sasca D, Hähnel PS, Szybinski J, Khawaja K, Kriege O, Pante SV, Bullinger L, Strand S, Strand D, Theobald M, Kindler T. SIRT1 prevents genotoxic stress-induced p53 activation in acute myeloid leukemia. Blood. 2014;124(1):121-33. doi: 10.1182/blood-2013-11-538819. 
Marquard JU*, Fischer K*, Baus K, Kashyap A, Ma S, Krupp M, Linke M, Teufel A, Zechner U, Strand D, Thorgeirsson SS, Galle PR, Strand S. SIRT6 dependent genetic and epigenetic alterations are associated with poor clinical outcome in HCC patients. Hepatology 2013 Mar 23,  doi: 10.1002/hep.26413. *equal first authorship

Carbajo-Pescador S, Steinmetz C, Kashyap A, Lorenz S, Mauriz JL, Heise M, Galle PR, González-Gallego J, Strand S. Melatonin induces transcriptional regulation of Bim by FoxO3a in HepG2 cells. Br J Cancer 2013, 108(2):442-9. doi: 10.1038/bjc.2012.563. 

Xia N, Strand S, Schlufter F, Siuda D, Reifenberg G, Kleinert H, Förstermann U, Li H. Role of SIRT1 and FOXO factors in eNOS transcriptional activation by resveratrol. Nitric Oxide. 2013 Aug 1;32:29-35. doi: 10.1016/j.niox.2013.04.001.

Kashyap A, Zimmermann T, Ergül N, Bosserhoff A, Hartman U, Alla V, Bataille F, Galle PR, Strand S* and Strand D*. The human Lgl polarity gene, Hugl-2, induces MET and suppresses Snail tumorgenesis. Oncogene 2012, doi: 10.1038/onc.2012.162. *equal senior authorship.

Natalio F, Kashyap A, Lorenz S, Kerschbaumer H, Dietzsch M, Tahir MN, Duschner H, Strand S, Strand D, Tremel W. Multi -photon imaging of amine-functionalized silica nanoparticles. Nanoscale. 2012 Aug 7;4(15):4680-6. doi: 10.1039/c2nr30660c.

Marcu-Malina V, Heijhuurs S, van Buuren M, Hartkamp L, Strand S, Sebestyen Z, Scholten K, Martens A, Kuball J. Redirecting ab T cells against cancer cells by transfer of a broadly tumor-reactive gd T cell receptor. Blood 2011; 118(1):50-9.

Teufel A, Maass T, Strand S, Kanzler S, Galante T, Becker K, Strand D, Biesterfeld S, Westphal H, Galle PR. Liver-specific Ldb1 deletion results in enhanced liver cancer development. J Hepatol. 2010; 53(6):1078-84.

Barreiros AP, Sprinzl M, Rosset S, Höhler T, Otto G, Theobald M, Galle PR, Strand D and Strand S (2009). EGF and HGF levels are increased during active HBV infection and enhance survival signaling through extracellular matrix interactions in primary human hepatocytes. Int J Cancer 2009, 124, 120-129.

Alla V, Kashyap A, Gregor S, Theobald M, Heid H, Galle PR, Strand D, Strand S. Human leukocyte elastase counteracts matrix metalloproteinase-7 induced apoptosis resistance of tumor cells. Cancer Lett. 2008, 268(2):331-9.

Zimmermann T, Kashyap A, Hartmann U, Otto G, Galle PR, Strand S, Strand D. Cloning and characterization of the promoter of Hugl-2, the human homologue of Drosophila lethal giant larvae (lgl) polarity gene. Biochem Biophys Res Commun. 2008, 366(4):1067-73.

Massimi P, Narayan N, Thomas M, Gammoh N, Strand S, Strand D, Banks L. Regulation of the hDlg/hScrib/Hugl-1 tumour suppressor complex. Exp Cell Res. 2008, 314(18):3306-17.

Su Z, Kuball J, Barreiros A-P, Gottfried D, Antunes Ferreira A, Theobald M, Galle PR, Strand D and Strand S. Nitric oxide promotes resistance to tumor suppression by CTLs, J. Immunol. 2006, 176, 3923-3930.

Expression of Hugl-1 is strongly reduced in malignant melanoma.Kuphal S, Wallner S, Schimanski CC, Bataille F, Hofer P, Strand S, Strand D, Bosserhoff AK. Oncogene. 2006 Jan 5;25(1):103-10.

Nair J*, Strand S,* Frank N*, Knauft J, Wesch H, Galle PR, Bartsch H.  Apoptosis and age-dependant induction of nuclear and mitochondrial etheno-DNA adducts in Long-Evans Cinnamon (LEC) rats: enhanced DNA damage by dietary curcumin upon copper accumulation. Carcinogenesis 2005, 26(7):1307-15. *equal first authorship

Strand , Strand D, Seufert R, Mann A, Lotz J, Blessing M, Lahn M, Wunsch A, Broering DC, Hahn U, Grischke E-M, Rogiers X, Otto G, Gores GJ, Galle PR. Placenta-derived CD95 ligand causes liver damage in hemolysis, elevated liver enzymes, and low platelet count syndrome, Gastroenterology 2004, 126:849-858.

Strand S, Vollmer P, van den Abeelen L, Gottfried D., Heid H, Kuball J, Theobald M, Galle PR, Strand D. Cleavage of CD95 by Matrix-Metalloproteinase-7 induces apoptosis resistance in tumor cells, Oncogene 2004, 23: 3732-3736.

Strand S, Hofmann WJ, Grambihler A, Hug H, Volkmann M, Otto G, Wesch H, Mariani SM, Stremmel W, Krammer PH, and Galle PR. Hepatic failure and liver cell damage in acute Wilson´s disease involve CD95 (APO-1/Fas) mediated apoptosis. Nature Med. 1998, 4: 588-593

Strand S, Hofmann WJ, Hug H, Müller M, Otto G, Mariani SM, Stremmel W, Krammer PH, and Galle PR. Lymphocyte apoptosis induced by CD95 (APO-1/Fas) ligand expressing tumor cells - A mechanism of immune evasion? Nature Med 1996, 2: 1361-1367