@article{HasegawaKapelyukhTaharaetal.2011, author = {Hasegawa, Maki and Kapelyukh, Yury and Tahara, Harunobu and Seibler, Jost and Rode, Anja and Krueger, Sylvia and Lee, Dongtao N. and Wolf, C. Roland and Scheer, Nico}, title = {Quantitative prediction of human pregnane X receptor and cytochrome P450 3A4 mediated drug-drug interaction in a novel multiple humanized mouse line}, series = {Molecular Pharmacology}, volume = {80}, journal = {Molecular Pharmacology}, number = {33}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/mol.111.071845}, pages = {518 -- 528}, year = {2011}, language = {en} } @article{JordanKruegerWillmesetal.2011, author = {Jordan, Sabine D. and Kr{\"u}ger, Markus and Willmes, Diana M. and Redemann, Nora and Wunderlich, F. Thomas and Br{\"o}nneke, Hella S. and Merkwirth, Carsten and Kashkar, Hamid and Olkkonen, Vesa M. and B{\"o}ttger, Thomas and Braun, Thomas and Seibler, Jost and Br{\"u}ning, Jens C.}, title = {Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism}, series = {Nature Cell Biology}, volume = {13}, journal = {Nature Cell Biology}, number = {4}, publisher = {Nature}, address = {New York}, issn = {1465-7392}, doi = {10.1038/ncb2211}, pages = {434 -- 446}, year = {2011}, abstract = {The contribution of altered post-transcriptional gene silencing to the development of insulin resistance and type 2 diabetes mellitus so far remains elusive. Here, we demonstrate that expression of microRNA (miR)-143 and 145 is upregulated in the liver of genetic and dietary mouse models of obesity. Induced transgenic overexpression of miR-143, but not miR-145, impairs insulin-stimulated AKT activation and glucose homeostasis. Conversely, mice deficient for the miR-143-145 cluster are protected from the development of obesity-associated insulin resistance. Quantitative-mass-spectrometry-based analysis of hepatic protein expression in miR-143-overexpressing mice revealed miR-143-dependent downregulation of oxysterol-binding-protein-related protein (ORP) 8. Reduced ORP8 expression in cultured liver cells impairs the ability of insulin to induce AKT activation, revealing an ORP8-dependent mechanism of AKT regulation. Our experiments provide direct evidence that dysregulated post-transcriptional gene silencing contributes to the development of obesity-induced insulin resistance, and characterize the miR-143-ORP8 pathway as a potential target for the treatment of obesity-associated diabetes.}, language = {en} } @article{GlaserLubitzLovelandetal.2009, author = {Glaser, Stefan and Lubitz, Sandra and Loveland, Kate L. and Ohbo, Kazu and Robb, Lorraine and Schwenk, Frieder and Seibler, Jost and Roellig, Daniela and Kranz, Andrea and Anastassiadis, Konstantinos and Stewart, A. Francis}, title = {The histone 3 lysine 4 methyltransferase, Mll2, is only required briefly in development and spermatogenesis}, series = {Epigenetics \& Chromatin}, volume = {2}, journal = {Epigenetics \& Chromatin}, number = {5}, issn = {1756-8935}, doi = {10.1186/1756-8935-2-5}, pages = {1 -- 16}, year = {2009}, language = {en} } @article{KotnikPopovaTodirasetal.2009, author = {Kotnik, Katarina and Popova, Elena and Todiras, Mihail and Mori, Marcelo A. and Alenina, Natalia and Seibler, Jost and Bader, Michael}, title = {Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown}, series = {Plos One}, volume = {4}, journal = {Plos One}, number = {4}, publisher = {Plos}, address = {San Francisco, California, US}, doi = {10.1371/journal.pone.0005124}, pages = {e5124}, year = {2009}, language = {en} } @article{HeroldBrandtSeibleretal.2008, author = {Herold, Marco J. and Brandt, Jens van den and Seibler, Jost and Reichardt, Holger M.}, title = {Inducible and reversible gene silencing by stable integration of an shRNA-encoding lentivirus in transgenic rats}, series = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {105}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {47}, issn = {1091-6490}, doi = {10.1073/pnas.0806213105}, pages = {18507 -- 18512}, year = {2008}, language = {en} } @article{KochWunderlichSeibleretal.2008, author = {Koch, Linda and Wunderlich, F. Thomas and Seibler, Jost and K{\"o}nner, A. Christine and Hampel, Brigitte and Irlenbusch, Sigrid and Brabant, Georg and Kahn, C. Ronald and Schwenk, Frieder and Br{\"u}ning, Jens C.}, title = {Central insulin action regulates peripheral glucose and fat metabolism in mice}, series = {The Journal of Clinical Investigation (JCI)}, volume = {118}, journal = {The Journal of Clinical Investigation (JCI)}, number = {6}, issn = {1558-8238}, doi = {10.1172/JCI31073}, pages = {2132 -- 2147}, year = {2008}, language = {en} } @article{ChristophBahrenbergVryetal.2008, author = {Christoph, Thomas and Bahrenberg, Gregor and Vry, Jean de and Englberger, Werner and Erdmann, Volker A. and Frech, Moritz and K{\"o}gel, Babette and R{\"o}hl, Thomas and Schiene, Klaus and Schr{\"o}der, Wolfgang and Seibler, Jost and Kurreck, Jens}, title = {Investigation of TRPV1 loss-of-function phenotypes in transgenic shRNA expressing and knockout mice}, series = {Molecular and Cellular Neuroscience}, volume = {37}, journal = {Molecular and Cellular Neuroscience}, number = {3}, issn = {1044-7431}, doi = {10.1016/j.mcn.2007.12.006}, pages = {579 -- 589}, year = {2008}, language = {en} } @article{CesariRennekampffVinterstenetal.2004, author = {Cesari, Francesca and Rennekampff, Verena and Vintersten, Kristina and Vuong, Lam Giang and Seibler, Jost and Bode, J{\"u}rgen and Wiebel, Franziska F. and Nordheim, Alfred}, title = {Elk-1 knock-out mice engineered by Flp recombinase-mediated cassette exchange}, series = {Genesis : The Journal of Genetics and Development}, volume = {38}, journal = {Genesis : The Journal of Genetics and Development}, number = {2}, issn = {1526-968X}, doi = {10.1002/gene.20003}, pages = {87 -- 92}, year = {2004}, language = {en} } @article{BodeSchlakeIberetal.2000, author = {Bode, J{\"u}rgen and Schlake, Thomas and Iber, Michaela and Sch{\"u}beler, Dirk and Seibler, Jost and Snezhkov, Evgeney and Nikolaev, Lev}, title = {The transgeneticist's toolbox: novel methods for the targeted modification of eukaryotic genomes}, series = {Biological Chemistry}, volume = {381}, journal = {Biological Chemistry}, number = {9-10}, issn = {1431-6730}, doi = {10.1515/BC.2000.103}, pages = {801 -- 813}, year = {2000}, language = {en} } @article{FengSeiblerAlamietal.1999, author = {Feng, Yong-Qing and Seibler, Jost and Alami, Raouf and Eisen, Andrew and Westerman, Karen A. and Leboulch, Philippe and Fiering, Steven and Bouhassira, Eric E.}, title = {Site-specific chromosomal integration in mammalian cells: highly efficient CRE recombinase-mediated cassette exchange}, series = {Journal of Molecular Biology}, volume = {292}, journal = {Journal of Molecular Biology}, number = {4}, issn = {0022-2836}, doi = {10.1006/jmbi.1999.3113}, pages = {779 -- 785}, year = {1999}, language = {en} } @article{SeiblerSchuebelerFieringetal.1998, author = {Seibler, Jost and Sch{\"u}beler, Dirk and Fiering, Steven and Groudine, Mark and Bode, J{\"u}rgen}, title = {DNA cassette exchange in ES cells mediated by Flp recombinase: an efficient strategy for repeated modification of tagged loci by marker-free constructs}, series = {Biochemistry}, volume = {37}, journal = {Biochemistry}, number = {18}, issn = {1520-4995}, doi = {10.1021/bi980288t}, pages = {6229 -- 6234}, year = {1998}, language = {en} } @article{SeiblerBode1997, author = {Seibler, Jost and Bode, J{\"u}rgen}, title = {Double-reciprocal crossover mediated by FLP-recombinase: a concept and an assay}, series = {Biochemistry}, volume = {36}, journal = {Biochemistry}, number = {7}, issn = {1520-4995}, pages = {1740 -- 1747}, year = {1997}, language = {en} } @article{BodeBartschBoulikasetal.1998, author = {Bode, J. and Bartsch, J. and Boulikas, T. and Iber, M. and Mielke, C. and Sch{\"u}beler, D. and Seibler, Jost and Benham, C.}, title = {Transcription-promoting genomic sites in mammalia: their elucidation and architectural principles}, series = {Gene therapy \& molecular biology}, volume = {1}, journal = {Gene therapy \& molecular biology}, number = {1}, issn = {1529-9120}, pages = {1 -- 29}, year = {1998}, language = {en} } @article{IberSchuebelerSeibleretal.1998, author = {Iber, Michaela and Sch{\"u}beler, Dirk and Seibler, Jost and H{\"o}xter, Maria and Bode, J{\"u}rgen}, title = {Efficient FACS selection procedure for cells undergoing Flp-mediated site-specific conversions}, series = {Technical Tips Online}, volume = {4}, journal = {Technical Tips Online}, number = {1}, doi = {10.1016/S1366-2120(08)70132-6}, pages = {25 -- 29}, year = {1998}, language = {en} } @article{HenkenOosterhuisOehlschlaegeretal.2012, author = {Henken, F. E. and Oosterhuis, K. and {\"O}hlschl{\"a}ger, Peter and Bosch, L. and Hooijberg, E. and Haanen, J. B. A. G. and Steenbergen, R. D. M.}, title = {Preclinical safety evaluation of DNA vaccines encoding modified HPV16 E6 and E7}, series = {Vaccine}, volume = {30}, journal = {Vaccine}, number = {28}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0264-410X}, doi = {10.1016/j.vaccine.2012.04.013}, pages = {4259 -- 4266}, year = {2012}, abstract = {Persistent infection with high-risk human papillomaviruses (hrHPV) can result in the formation of anogenital cancers. As hrHPV proteins E6 and E7 are required for cancer initiation and maintenance, they are ideal targets for immunotherapeutic interventions. Previously, we have described the development of DNA vaccines for the induction of HPV16 E6 and E7 specific T cell immunity. These vaccines consist of 'gene-shuffled' (SH) versions of HPV16 E6 and E7 that were fused to Tetanus Toxin Fragment C domain 1 (TTFC) and were named TTFC-E6SH and TTFC-E7SH. Gene-shuffling was performed to avoid the risk of inducing malignant transformation at the vaccination site. Here, we describe the preclinical safety evaluation of these candidate vaccines by analysis of their transforming capacity in vitro using established murine fibroblasts (NIH 3T3 cells) and primary human foreskin keratinocytes (HFKs). We demonstrate that neither ectopic expression of TTFC-E6SH and TTFC-E7SH alone or in combination enabled NIH 3T3 cells to form colonies in soft agar. In contrast, expression of HPV16 E6WT and E7WT alone or in combination resulted in effective transformation. Similarly, retroviral transduction of HFKs from three independent donors with both TTFC-E6SH and TTFC-E7SH alone or in combination did not show any signs of immortalization. In contrast, the combined expression of E6WT and E7WT induced immortalization in HFKs from all donors. Based on these results we consider it justified to proceed to clinical evaluation of DNA vaccines encoding TTFC-E6SH and TTFC-E7SH in patients with HPV16 associated (pre)malignancies.}, language = {en} } @article{ImmelGruetzkeSpaeteetal.2012, author = {Immel, Timo and Gr{\"u}tzke, Martin and Sp{\"a}te, Anne-Katrin and Groth, Ulrich and {\"O}hlschl{\"a}ger, Peter and Huhn, Thomas}, title = {Synthesis and X-ray structure analysis of a heptacoordinate titanium(IV)-bis-chelate with enhanced in vivo antitumor efficacy}, series = {Chemical Communications}, volume = {48}, journal = {Chemical Communications}, number = {46}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1364-548X}, doi = {10.1039/C2CC31624B}, pages = {5790 -- 5792}, year = {2012}, abstract = {Chelate stabilization of a titanium(IV)-salan alkoxide by ligand exchange with 2,6-pyridinedicarboxylic acid (dipic) resulted in heptacoordinate complex 3 which is not redox-active, stable on silica gel and has increased aqueous stability. 3 is highly toxic in HeLa S3 and Hep G2 and has enhanced antitumor efficacy in a mouse cervical-cancer model.}, language = {en} } @article{ScheerSnaithWolfetal.2013, author = {Scheer, Nico and Snaith, Mike and Wolf, C. Roland and Seibler, Jost}, title = {Generation and utility of genetically humanized mouse models}, series = {Drug Discovery Today}, volume = {Vol 18}, journal = {Drug Discovery Today}, number = {23-24}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1359-6446}, doi = {10.1016/j.drudis.2013.07.007}, pages = {1200 -- 1211}, year = {2013}, language = {en} } @article{BouwmanGuldenHeijdenetal.2013, author = {Bouwman, Peter and Gulden, Hanneke van der and Heijden, Ingrid van der and Drost, Rinske and Klijn, Christiaan N. and Prasetyanti, Pramudita and Pieterse, Mark and Wientjens, Ellen and Seibler, Jost and Hogervorst, Frank B. L. and Jonkers, Jos}, title = {A High-Throughput Functional Complementation Assay for Classification of BRCA1 Missense Variants}, series = {Cancer Discovery}, journal = {Cancer Discovery}, number = {3}, issn = {2159-8290}, doi = {10.1158/2159-8290.CD-13-0094}, pages = {1142 -- 1152}, year = {2013}, language = {en} } @article{MichalakNacerddinePietersenetal.2013, author = {Michalak, Ewa Malgorzata and Nacerddine, Karim and Pietersen, Alexandra and Beuger, Vincent and Pawlitzky, Inka and Cornelissen-Steijger, Paulien and Wientjens, Ellen and Tanger, Ellen and Seibler, Jost and Lohuizen, Maarten van and Jonkers, Jos}, title = {Polycomb group gene Ezh2 regulates mammary gland morphogenesis and maintains the luminal progenitor pool}, series = {Stem Cells}, volume = {Vol 31}, journal = {Stem Cells}, number = {9}, publisher = {Oxford University Press}, address = {Oxford}, issn = {1549-4918}, doi = {10.1002/stem.1437}, pages = {1910 -- 1920}, year = {2013}, language = {en} } @article{GebeshuberKornauthDongetal.2013, author = {Gebeshuber, Christoph A. and Kornauth, Christoph and Dong, Lihua and Sierig, Ralph and Seibler, Jost and Reiss, Martina and Tauber, Stefanie and Bilban, Martin and Wang, Shijun and Kain, Renate and B{\"o}hmig, Georg A. and Moeller, Marcus J. and Gr{\"o}ne, Hermann-Josef and Englert, Christoph and Martinez, Javier and Kerjaschki, Dontscho}, title = {Focal segmental glomerulosclerosis is induced by microRNA-193a and its downregulation of WT1}, series = {Nature Medicine}, volume = {19}, journal = {Nature Medicine}, number = {4}, issn = {1078-8956}, doi = {10.1038/nm.3142}, pages = {481 -- 487}, year = {2013}, language = {en} }