TY  - JOUR
A1  - Hasegawa, Maki
A1  - Kapelyukh, Yury
A1  - Tahara, Harunobu
A1  - Seibler, Jost
A1  - Rode, Anja
A1  - Krueger, Sylvia
A1  - Lee, Dongtao N.
A1  - Wolf, C. Roland
A1  - Scheer, Nico
T1  - Quantitative prediction of human pregnane X receptor and cytochrome P450 3A4 mediated drug-drug interaction in a novel multiple humanized mouse line
JF  - Molecular Pharmacology
Y1  - 2011
U6  - https://doi.org/10.1124/mol.111.071845
SN  - 1521-0111
VL  - 80
IS  - 33
SP  - 518
EP  - 528
PB  - ASPET
CY  - Bethesda, Md.
ER  - 
TY  - JOUR
A1  - Jordan, Sabine D.
A1  - Krüger, Markus
A1  - Willmes, Diana M.
A1  - Redemann, Nora
A1  - Wunderlich, F. Thomas
A1  - Brönneke, Hella S.
A1  - Merkwirth, Carsten
A1  - Kashkar, Hamid
A1  - Olkkonen, Vesa M.
A1  - Böttger, Thomas
A1  - Braun, Thomas
A1  - Seibler, Jost
A1  - Brüning, Jens C.
T1  - Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism
JF  - Nature Cell Biology
N2  - 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.
Y1  - 2011
U6  - https://doi.org/10.1038/ncb2211
SN  - 1465-7392
VL  - 13
IS  - 4
SP  - 434
EP  - 446
PB  - Nature
CY  - New York
ER  - 
TY  - JOUR
A1  - Glaser, Stefan
A1  - Lubitz, Sandra
A1  - Loveland, Kate L.
A1  - Ohbo, Kazu
A1  - Robb, Lorraine
A1  - Schwenk, Frieder
A1  - Seibler, Jost
A1  - Roellig, Daniela
A1  - Kranz, Andrea
A1  - Anastassiadis, Konstantinos
A1  - Stewart, A. Francis
T1  - The histone 3 lysine 4 methyltransferase, Mll2, is only required briefly in development and spermatogenesis
JF  - Epigenetics & Chromatin
Y1  - 2009
U6  - https://doi.org/10.1186/1756-8935-2-5
SN  - 1756-8935
VL  - 2
IS  - 5
SP  - 1
EP  - 16
ER  - 
TY  - JOUR
A1  - Kotnik, Katarina
A1  - Popova, Elena
A1  - Todiras, Mihail
A1  - Mori, Marcelo A.
A1  - Alenina, Natalia
A1  - Seibler, Jost
A1  - Bader, Michael
T1  - Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown
JF  - Plos One
Y1  - 2009
U6  - https://doi.org/10.1371/journal.pone.0005124
VL  - 4
IS  - 4
SP  - e5124
PB  - Plos
CY  - San Francisco, California, US
ER  - 
TY  - JOUR
A1  - Herold, Marco J.
A1  - Brandt, Jens van den
A1  - Seibler, Jost
A1  - Reichardt, Holger M.
T1  - Inducible and reversible gene silencing by stable integration of an shRNA-encoding lentivirus in transgenic rats
JF  - Proceedings of the National Academy of Sciences of the United States of America
Y1  - 2008
U6  - https://doi.org/10.1073/pnas.0806213105
SN  - 1091-6490
VL  - 105
IS  - 47
SP  - 18507
EP  - 18512
ER  - 
TY  - JOUR
A1  - Koch, Linda
A1  - Wunderlich, F. Thomas
A1  - Seibler, Jost
A1  - Könner, A. Christine
A1  - Hampel, Brigitte
A1  - Irlenbusch, Sigrid
A1  - Brabant, Georg
A1  - Kahn, C. Ronald
A1  - Schwenk, Frieder
A1  - Brüning, Jens C.
T1  - Central insulin action regulates peripheral glucose and fat metabolism in mice
JF  - The Journal of Clinical Investigation (JCI)
Y1  - 2008
U6  - https://doi.org/10.1172/JCI31073
SN  - 1558-8238
VL  - 118
IS  - 6
SP  - 2132
EP  - 2147
ER  - 
TY  - JOUR
A1  - Christoph, Thomas
A1  - Bahrenberg, Gregor
A1  - Vry, Jean de
A1  - Englberger, Werner
A1  - Erdmann, Volker A.
A1  - Frech, Moritz
A1  - Kögel, Babette
A1  - Röhl, Thomas
A1  - Schiene, Klaus
A1  - Schröder, Wolfgang
A1  - Seibler, Jost
A1  - Kurreck, Jens
T1  - Investigation of TRPV1 loss-of-function phenotypes in transgenic shRNA expressing and knockout mice
JF  - Molecular and Cellular Neuroscience
Y1  - 2008
U6  - https://doi.org/10.1016/j.mcn.2007.12.006
SN  - 1044-7431
VL  - 37
IS  - 3
SP  - 579
EP  - 589
ER  - 
TY  - JOUR
A1  - Cesari, Francesca
A1  - Rennekampff, Verena
A1  - Vintersten, Kristina
A1  - Vuong, Lam Giang
A1  - Seibler, Jost
A1  - Bode, Jürgen
A1  - Wiebel, Franziska F.
A1  - Nordheim, Alfred
T1  - Elk-1 knock-out mice engineered by Flp recombinase-mediated cassette exchange
JF  - Genesis : The Journal of Genetics and Development
Y1  - 2004
U6  - https://doi.org/10.1002/gene.20003
SN  - 1526-968X
VL  - 38
IS  - 2
SP  - 87
EP  - 92
ER  - 
TY  - JOUR
A1  - Bode, Jürgen
A1  - Schlake, Thomas
A1  - Iber, Michaela
A1  - Schübeler, Dirk
A1  - Seibler, Jost
A1  - Snezhkov, Evgeney
A1  - Nikolaev, Lev
T1  - The transgeneticist's toolbox: novel methods for the targeted modification of eukaryotic genomes
JF  - Biological Chemistry
Y1  - 2000
U6  - https://doi.org/10.1515/BC.2000.103
SN  - 1431-6730
VL  - 381
IS  - 9-10
SP  - 801
EP  - 813
ER  - 
TY  - JOUR
A1  - Feng, Yong-Qing
A1  - Seibler, Jost
A1  - Alami, Raouf
A1  - Eisen, Andrew
A1  - Westerman, Karen A.
A1  - Leboulch, Philippe
A1  - Fiering, Steven
A1  - Bouhassira, Eric E.
T1  - Site-specific chromosomal integration in mammalian cells: highly efficient CRE recombinase-mediated cassette exchange
JF  - Journal of Molecular Biology
Y1  - 1999
U6  - https://doi.org/10.1006/jmbi.1999.3113
SN  - 0022-2836
VL  - 292
IS  - 4
SP  - 779
EP  - 785
ER  - 
TY  - JOUR
A1  - Seibler, Jost
A1  - Schübeler, Dirk
A1  - Fiering, Steven
A1  - Groudine, Mark
A1  - Bode, Jürgen
T1  - DNA cassette exchange in ES cells mediated by Flp recombinase: an efficient strategy for repeated modification of tagged loci by marker-free constructs
JF  - Biochemistry
Y1  - 1998
U6  - https://doi.org/10.1021/bi980288t
SN  - 1520-4995
VL  - 37
IS  - 18
SP  - 6229
EP  - 6234
ER  - 
TY  - JOUR
A1  - Seibler, Jost
A1  - Bode, Jürgen
T1  - Double-reciprocal crossover mediated by FLP-recombinase: a concept and an assay
JF  - Biochemistry
Y1  - 1997
SN  - 1520-4995
VL  - 36
IS  - 7
SP  - 1740
EP  - 1747
ER  - 
TY  - JOUR
A1  - Bode, J.
A1  - Bartsch, J.
A1  - Boulikas, T.
A1  - Iber, M.
A1  - Mielke, C.
A1  - Schübeler, D.
A1  - Seibler, Jost
A1  - Benham, C.
T1  - Transcription-promoting genomic sites in mammalia: their elucidation and architectural principles
JF  - Gene therapy & molecular biology
Y1  - 1998
SN  - 1529-9120
VL  - 1
IS  - 1
SP  - 1
EP  - 29
ER  - 
TY  - JOUR
A1  - Iber, Michaela
A1  - Schübeler, Dirk
A1  - Seibler, Jost
A1  - Höxter, Maria
A1  - Bode, Jürgen
T1  - Efficient FACS selection procedure for cells undergoing Flp-mediated site-specific conversions
JF  - Technical Tips Online
Y1  - 1998
U6  - https://doi.org/10.1016/S1366-2120(08)70132-6
VL  - 4
IS  - 1
SP  - 25
EP  - 29
ER  - 
TY  - JOUR
A1  - Henken, F. E.
A1  - Oosterhuis, K.
A1  - Öhlschläger, Peter
A1  - Bosch, L.
A1  - Hooijberg, E.
A1  - Haanen, J. B. A. G.
A1  - Steenbergen, R. D. M.
T1  - Preclinical safety evaluation of DNA vaccines encoding modified HPV16 E6 and E7
JF  - Vaccine
N2  - 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.
Y1  - 2012
U6  - https://doi.org/10.1016/j.vaccine.2012.04.013
SN  - 0264-410X
VL  - 30
IS  - 28
SP  - 4259
EP  - 4266
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Immel, Timo
A1  - Grützke, Martin
A1  - Späte, Anne-Katrin
A1  - Groth, Ulrich
A1  - Öhlschläger, Peter
A1  - Huhn, Thomas
T1  - Synthesis and X-ray structure analysis of a heptacoordinate titanium(IV)-bis-chelate with enhanced in vivo antitumor efficacy
JF  - Chemical Communications
N2  - 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.
Y1  - 2012
U6  - https://doi.org/10.1039/C2CC31624B
SN  - 1364-548X
VL  - 48
IS  - 46
SP  - 5790
EP  - 5792
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Scheer, Nico
A1  - Snaith, Mike
A1  - Wolf, C. Roland
A1  - Seibler, Jost
T1  - Generation and utility of genetically humanized mouse models
JF  - Drug Discovery Today
Y1  - 2013
U6  - https://doi.org/10.1016/j.drudis.2013.07.007
SN  - 1359-6446
VL  - Vol 18
IS  - 23-24
SP  - 1200
EP  - 1211
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Bouwman, Peter
A1  - Gulden, Hanneke van der
A1  - Heijden, Ingrid van der
A1  - Drost, Rinske
A1  - Klijn, Christiaan N.
A1  - Prasetyanti, Pramudita
A1  - Pieterse, Mark
A1  - Wientjens, Ellen
A1  - Seibler, Jost
A1  - Hogervorst, Frank B. L.
A1  - Jonkers, Jos
T1  - A High-Throughput Functional Complementation Assay for Classification of BRCA1 Missense Variants
JF  - Cancer Discovery
Y1  - 2013
U6  - https://doi.org/10.1158/2159-8290.CD-13-0094
SN  - 2159-8290
IS  - 3
SP  - 1142
EP  - 1152
ER  - 
TY  - JOUR
A1  - Michalak, Ewa Malgorzata
A1  - Nacerddine, Karim
A1  - Pietersen, Alexandra
A1  - Beuger, Vincent
A1  - Pawlitzky, Inka
A1  - Cornelissen-Steijger, Paulien
A1  - Wientjens, Ellen
A1  - Tanger, Ellen
A1  - Seibler, Jost
A1  - Lohuizen, Maarten van
A1  - Jonkers, Jos
T1  - Polycomb group gene Ezh2 regulates mammary gland morphogenesis and maintains the luminal progenitor pool
JF  - Stem Cells
Y1  - 2013
U6  - https://doi.org/10.1002/stem.1437
SN  - 1549-4918
VL  - Vol 31
IS  - 9
SP  - 1910
EP  - 1920
PB  - Oxford University Press
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Gebeshuber, Christoph A.
A1  - Kornauth, Christoph
A1  - Dong, Lihua
A1  - Sierig, Ralph
A1  - Seibler, Jost
A1  - Reiss, Martina
A1  - Tauber, Stefanie
A1  - Bilban, Martin
A1  - Wang, Shijun
A1  - Kain, Renate
A1  - Böhmig, Georg A.
A1  - Moeller, Marcus J.
A1  - Gröne, Hermann-Josef
A1  - Englert, Christoph
A1  - Martinez, Javier
A1  - Kerjaschki, Dontscho
T1  - Focal segmental glomerulosclerosis is induced by microRNA-193a and its downregulation of WT1
JF  - Nature Medicine
Y1  - 2013
U6  - https://doi.org/10.1038/nm.3142
SN  - 1078-8956
VL  - 19
IS  - 4
SP  - 481
EP  - 487
ER  -