GRK 1331:  Cell-based Characterisation of Disease Mechanisms in Tissue Destruction and Repair

• Subject Area: Medicine
• Term: from 2006 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 16011279

• Final Report Year: 2015

Final Report Abstract

The RTG 1331 was set up to cover a wide range of biomedical topics, so that the involved doctoral researchers got a broad background on mechanisms, scientific approaches and technical solutions from different areas of disease biology. Examples for interdisciplinary research outcomes resulting from the combination of disciplines in the RTG are the finding i) that DNA repair mechanisms, commonly investigated in tumour biology, play a role in neurodegeneration; ii) that the application of riboswitches, designed for synthetic biology applications, could be practically applied to generate improved models for research in lung disease (e.g asthma); iii) that knowledge from the fields of skin regeneration could be used to understand the hepatic repair response after toxic damage. Over its runtime, the research of the RTG evolved from initially simple model systems towards the transfer of this knowledge to more complex systems such as 3-dimensional tissue culture, cell-cell interactions in culture dishes or model organisms, and to a transition from single endpoints to more systems-wide approaches that used modern Omics technologies. The broad range of medically-relevant disease biology research topics that was covered by > 140 RTG publications comprises: neurodegeneration (Alzheimer’s and Parkinson’s disease, as well as neuro-inflammation), infection and immunity (antigen processing and presentation, immune cell migration, bacteria-host cell interactions), tumour biology (DNA damage and repair, oncogene characterization, tumour vaccination), toxicology (epigenetic mechanisms, stem cell models, environmental toxicants of industrial or natural origin; use of transcriptomics to characterize toxicant responses), lung diseases (chronic obstructive pulmonary disease and asthma), developmental processes (regeneration of skin, liver, fish fins and growth of neural tissue components) and pharmacological model development (organoids, transgenic mouse models using viral vectors, human cells and their progeny/derivatives). In six areas, the RTG produced cutting edge research output recognized internationally: i) Development of alternative methods to animal testing (e.g. 3D intestinal organoids; functional tests for human neural differentiation); ii) Advanced imaging approaches (e.g. construction and use of femtosecond pulse-lasers to produce defined DNA lesions); iii) Research on functions of the recently-discovered oncogene DEK; iv) DNA repair in skin and blood cells; v) Development of new cell models (e.g. human neurons) and test systems (e.g. adenoassociated virus based genetic modification of mouse respiratory tract, or assessment of neurite network integrity by high content imaging); vi) Immune response and infection (e.g. the reciprocal interactions of pathogens and host cells; a strong research line addressed the migration of immune cells and the underlying signalling). The RTG was well-integrated with other national and international research. Particularly notable is the interaction with researchers from Baltimore (Johns-Hopkins University (JHU) and NIH). For instance, Thomas Hartung from the Bloomberg School of Public Health at JHU was a direct partner of the RTG. In this function, he hosted students and provided expertise and input for metabolomics, infection biology and development of alternative methods.

Publications

• (2006) Age-associated cellular relocation of Sod 1 as a self-defense is a futile mechanism to prevent vascular aging. Biochem Biophys Res Commun. 344:972-980
  van der Loo B, Bachschmid M, Skepper JN, Labugger R, Schildknecht S, Hahn R, Müssig E, Gygi D, Lüscher TF
  
• (2006) Autocatalytic tyrosine nitration of prostaglandin endoperoxide synthase-2 in LPS-stimulated RAW 264.7 macrophages. Biochem Biophys Res Commun.340:318-325
  Schildknecht S, Heinz K, Daiber A, Hamacher J, Kavaklí C, Ullrich V, Bachschmid M
  
• (2006) Flow-cytometric assessment of cellular poly(ADP- ribosyl)ation capacity in peripheral blood lymphocytes. Immun Ageing;3:8
  Kunzmann A, Liu D, Annett K, et al.
  
• (2006) Identification of Borrelia burgdorferi ribosomal protein L25 by the phage surface display method and evaluation of the protein's value for serodiagnosis. J Clin Microbiol. 44:3778-3780
  Mueller M, Bunk S, et al.
  
• (2006) In vitro pyrogen test for toxic or immunomodulatory drugs. J Immunol Meth, 313:169-175
  Daneshian M, Guenther A, Wendel A, Hartung T, and von Aulock S
  
• (2007) Activation of an alternative death receptor-induced signaling pathway in human hepatocytes under caspase arrest. Arch Biochem Biophys 462: 140-149
  Dünstl G., Weiland T.,Schlaeger C., Nüssler A., Künstle G., Wendel A
  
• (2007) Endothelial cells are protected against phagocyte-transmitted Chlamydophila pneumoniae infections by laminar shear stress: Shear stress protects from C. pneumoniae infection. Atherosclerosis, 198: 256 – 263
  Gueinzius K, Magenau A, Erath S, Wittke V, Urbich C, Ferrando-May E, Dimmeler S, Hermann C
  
• (2007) Human embryonic stem cells elicit an immune regulatory phenotype by upregulating CTLA-4 and IL-10 expression in T cells. J Stem Cells Regen Med. 2(1):27-8
  Ajjikuttira P, Wong S, Penzkofer S, Ying J, Kadereit S
  
• (2007) Immune control by endocannabinoids - new mechanisms of neuroprotection? J Neuroimmunol. 184:127-135
  Ullrich O, Merker K, Timm J, Tauber S
  
• (2007) Role of reduced lipoic acid in the redox regulation of mitochondrial aldehyde dehydrogenase (ALDH-2) activity. Implications for mitochondrial oxidative stress and nitrate tolerance. J Biol Chem. 282:792-799
  Wenzel P, Hink U, Oelze M, Schuppan S, Schaeuble K, Schildknecht S, Ho KK, Weiner H, Bachschmid M, Münzel T, Daiber A
  
• (2007) The influence of folic acid depletion on the Nucleotide Excision Repair capacity of human dermal fibroblasts measured by a modified Host Cell Reactivation Assay. Biofactors; 31:181-190
  Burger K, Kieser N, Gallinat S, Mielke H, Knott S, Bergemann J
  
• (2007) Use of synthetic derivatives to determine the minimal active structure of cytokine-inducing LTA Clin Vaccine Immunol. 14:1629-1633
  Deininger S, Figueroa-Perez I, Sigel S, Stadelmaier A, Schmidt RR, Hartung T, von Aulock S
  
• Apoptotic signaling beyond caspase activation in hepatocytes, Konstanz, Univ., Diss., 2007
  Weiland, Timo
  
• Immune response in persistent bacterial infections - Identification of Borrelia burgdorferi sensu lato and Chlamydia pneumoniae antigens, Konstanz, Univ., Diss., 2007
  Bunk, Sebastian
  
• (2008) A UVB fingerprint mutation on the p53 tumor suppressor gene decreases in vitro.Zhang Z, J.Cells Tissues Organs.;188:280-286
  Burger K, Hellwig S, Bergemann
  
• (2008) Acetaminophen inhibits prostanoid synthesis by scavenging the PGHS-activator peroxynitrite. FASEB J. 22:215-224
  Schildknecht S, Daiber A, Ghisla S, Cohen RA, Bachschmid MM
  
• (2008) CNS immune surveillance and neuroinflammation: endocannabinoids keep control. Curr Pharm Des;14:2266-2278
  Wolf SA, Tauber S, Ullrich O
  
• (2008) Cytokine induction by Gram-positive Bacteria, Immunobiology; 213:285-296
  Draing C, Sigel S, Deininger S, Traub S, Munke R, Mayer C, Hareng L, Hartung T, von Aulock S, Hermann C
  
• (2008) DEK is a poly(ADP-ribose) acceptor in apoptosis and mediates resistance to genotoxic stress. Mol.Cell. Biol. 28: 3245–3257
  Kappes F, Fahrer J, Khodadoust MS, Tabbert A, Strasser C, Mor-Vaknin N, Moreno-Villanueva M, Bürkle A, Markovitz DM, and Ferrando-May E
  
• (2008) Effect of zinc on cellular poly(ADP-ribosyl)ation capacity. Exp Gerontol ;43:409-414
  Kunzmann A, Dedoussis G, Jajte J, Malavolta M, Mocchegiani E, Bürkle A
  
• (2008) Endogenous peroxynitrite modulates PGHS-1-dependent thromboxane A2 formation and aggregation in human platelets. Free Radic Biol Med. 45:512-520
  Schildknecht S, van der Loo B, Weber K, Tiefenthaler K, Daiber A, Bachschmid MM
  
• (2008) Fgfr1 signalling in the development of a sexually selected trait in vertebrates, the sword of swordtail fish. BMC Developmental Biology 8:98
  Offen N, Blum N, Meyer A, Begemann G
  
• (2008) Food for thought... on the real success of 3R approaches. ALTEX.;25:17-32
  Leist M, Kadereit S, Schildknecht S
  
• (2008) High sensitivity pyrogen testing in water and dialysis solutions. J Immunol Meth. 336:64-70
  Daneshian M, Wendel A, Hartung T, and von Aulock S
  
• (2008) IL-10 release requires stronger toll-like receptor 4-triggering than TNF- a possible explanation for the selective effects of heterozygous TLR4 polymorphism Asp(299)Gly on IL-10 release. Immunobiology; 213:621-627
  Dehus, O., Bunk S., v. Aulock S. and Hermann C.
  
• (2008) Imidazoquinolinone, imidazopyridine, and isoquinolindione derivatives as novel and potent inhibitors of the poly(ADP-ribose) polymerase (PARP): a comparison with standard PARP inhibitors. Mol. Pharmacol.; 74: 1587-1598
  Eltze T, Boer R, Wagner T, Weinbrenner S, McDonald MC, Thiemermann C, Bürkle A, Klein T
  
• (2008) Imidazoquinolinone, imidazopyridine, and isoquinolindione derivatives as novel and potent inhibitors of the poly(ADP-ribose) polymerase (PARP): a comparison with standard PARP inhibitors. Mol. Pharmacol.; 74: 1587-1598
  Eltze T, Boer R, Wagner T, Weinbrenner S, McDonald MC, Thiemermann C, Bürkle A, Klein T
  
• (2008) Immunoproteomic identification and serological responses to novel Chlamydia pneumoniae antigens that are associated with persistent C. pneumoniae infections. J Immunol.; 180:5490-5498
  Bunk S, Susnea I, et al.
  
• (2008) Iodide accumulation provides kelp with an inorganic antioxidant impacting atmospheric chemistry Proc Natl Acad Sci USA. 105:6954-6958
  Küpper FC, Carpenter LJ, McFiggans GB, Palmer CJ, Waite TJ, Boneberg EM, Woitsch S, Weiller M, Abela R, Grolimund D, Potin P, Butler A, Luther GW 3rd, Kroneck PM, Meyer-Klaucke W, Feiters MC
  
• (2008). The Nrf2 transcription factor protects from toxin-induced liver injury and fibrosis. Lab Invest 88:1068-1078
  Xu W, Hellerbrand C, Köhler UA, Bugnon P, Kann YW, Werner S and Beyer TA
  
• Human Poly(ADP-Ribose) Polymerase-1-Expressing Embryonic Stem Cells and Mice - Generation and Phenotypic Characterization, Konstanz, Univ., Diss., 2008
  Mangerich, Aswin
  
• Receptor polymorphisms and non-classical immune stimuli in bacterial immune recognition, Konstanz, Univ., Diss., 2008
  Dehus, Oliver
  
• (2009) A caveat in mouse genetic engineering: ectopic gene targeting in ES cells by bidirectional extension of the homology arms of a gene replacement vector carrying human PARP-1. Transgenic Research 18:261-279
  Mangerich A, Scherthan H, Diefenbach J, Kloz U, van der Hoeven F, Beneke S, and A. Bürkle
  
• (2009) Amplification of lipopolysaccharide-induced cytokine synthesis in non-small cell lung cancer/neutrophil cocultures. Mol Cancer Res. 7(10):1729-35
  Grandel U, Heygster D, Sibelius U, Fink L, Sigel S, Seeger W, Grimminger F, Hattar K
  
• (2009) Antitumor effects of a combined 5-aza-2'deoxycytidine and valproic acid treatment on rhabdomyosarcoma and medulloblastoma in Ptch mutant mice. Cancer Res. ;69:887-895
  Ecke I, Petry F, Rosenberger A, Tauber S, Mönkemeyer S, Hess I, Dullin C, Kimmina S, Pirngruber J, Johnsen SA, Uhmann A, Nitzki F, Wojnowski L, Schulz-Schaeffer W, Witt O, Hahn H
  
• (2009) Artificial ribozyme switches containing natural riboswitch aptamer domains. Angew Chem Int Ed Engl. 48(15):2715-8
  Wieland M, Benz A, Klauser B, Hartig JS
  
• (2009) Assessment of pyrogenic contaminations with validated human whole-blood assay. Nat Protoc 4(12):1709-21
  Daneshian M, von Aulock S, Hartung T
  
• (2009) Chemical model systems for cellular nitros(yl)ation reactions. Free Radic Biol Med. 47:458-467
  Daiber A, Schildknecht S, Müller J, Kamuf J, Bachschmid MM, Ullrich V
  
• (2009) Development, validation and applications of the monocyte activation test for pyrogens based on human whole blood. ALTEX. 26(4):265-77
  Schindler S, von Aulock S, Daneshian M, Hartung T
  
• (2009) Do leucocytes reflect condition in nestling burrowing parrots Cyanoliseus patagonus in the wild? Comp Biochem Physiol A Mol Integr Physiol 152(2): 176-81
  Masello J.F., Choconi R. G., Helmer M., Kremberg T., Lubjuhn T. and Quillfeldt P.
  
• (2009) Impaired TLR-2 expression and TLR-2-mediated cytokine secretion in macrophages from patients with atopic dermatitis. Allergy. 64(11):1580-7
  Niebuhr M, Lutat C, Sigel S, Werfel T
  
• (2009) Measurement of cellular beta-site of APP cleaving enzyme 1 activity and its modulation in neuronal assay systems. Anal Biochem. 387:208-220
  Volbracht C, Penzkofer S, Mansson D, Christensen KV, Fog K, Schildknecht S, Leist M, Nielsen J
  
• (2009) Monitoring white blood cell mitochondrial aldehyde dehydrogenase activity: implications for nitrate therapy in humans. J Pharmacol Exp Ther. 330:63-71
  Wenzel P, Schulz E, Gori T, Ostad MA, Mäthner F, Schildknecht S, Göbel S, Oelze M, Stalleicken D, Warnholtz A, Münzel T, Daiber A
  
• (2009) Oatp-associated uptake and toxicity of microcystins in primary murine whole brain cells. Toxicology and Applied Pharmacology 234: 247-255
  Feurstein D, Holst K, Fischer A, Dietrich DR
  
• (2009) Peroxynitrite as regulator of vascular prostanoid synthesis. Arch Biochem Biophys. 484:183-189
  Schildknecht S, Ullrich V
  
• (2009) Probiotic Escherichia coli Nissle 1917 suppresses allergen-induced Th2 responses in the airways. Int Arch Allergy Immunol, 149(3):219-30
  Bickert T, Trujillo-Vargas CM, Duechs M, Wohlleben G, Polte T, Hansen G, Oelschlaeger TA, Erb KJ
  
• (2009) Requirement of a dopaminergic neuronal phenotype for toxicity of low concentrations of 1-methyl-4- phenylpyridinium to human cells. Toxicol Appl Pharmacol. 241(1):23-35
  Schildknecht S, Pöltl D, Nagel DM, Matt F, Scholz D, Lotharius J, Schmieg N, Salvo-Vargas A, Leist M
  
• (2009) Requirement of a dopaminergic neuronal phenotype for toxicity of low concentrations of 1-methyl-4-phenylpyridinium to human cells. Toxicology and Applied Pharmacology 241(1):23-35
  Schildknecht S, Poeltl D, Nagel DM, Matt F, Scholz D, Lotharius J, Salvo-Vargas A, Schmieg N, Leist M
  
• (2009) Sensitization by 5-azacytidine toward death receptor-induced hepatic apoptosis. J Pharmacol Exp Ther,. 328: 107-115
  Weiland T, Weiller M, Künstle G, Wendel A
  
• (2009) Sensitization by 5-azacytidine toward death receptor-induced hepatic apoptosis. J Pharmacol Exp Ther. 328(1):107-15
  Weiland T, Weiller M, Künstle G, Wendel A
  
• (2009) Signalling processes in endothelial ageing in relation to chronic oxidative stress and their potential therapeutic implications in humans. Exp Physiol. 94:305-310
  van der Loo B, Schildknecht S, Zee R, Bachschmid MM
  
• Biological consequences of alteration of cellular Poly(ADP-ribose) polymerase-1 expression in rodent cells, Konstanz, Univ., Diss., 2009
  Eltze, Tobias
  
• Erkennung von Staphylococcus-aureus-Zellwandkomponenten durch das angeborene Immunsystem : strukturelle und funktionelle Voraussetzungen, Konstanz, Univ., Diss., 2009
  Sigel, Stefanie
  
• Internalization of fibronectin-binding S. aureus into mammalian cells via integrins and membrane microdomains, Konstanz, Univ., Diss., 2009
  Hoffmann, Christine
  
• Role of inducible Nitric Oxide Synthase and Histone Deacetylase in Human Lung Epithelial Cell Model of Inflammation and Steroid Insensitivity, Konstanz, Univ., Diss., 2009
  Liu, Dan
  
• Selective induction of apoptosis via the TNF system in hepatocellular carcinoma, Konstanz, Univ., Diss., 2009
  Speicher, Tobias
  
• Strategies to Potentiate the Cellular Poly(ADP-ribosyl)ation Response to DNA Damage, Konstanz, Univ., Diss., 2009
  Kunzmann, Andrea
  
• The individual and combined neurotoxic effects of cyanobacterial toxins, Konstanz, Univ., Diss., 2009
  Feurstein, Daniel
  
• (2010) A modified fluorimetric host cell reactivation assay to determine the repair capacity of primary keratinocytes, melanocytes and fibroblasts BMC Biotechnol. 10:46
  Burger K, Matt K, Kieser N, Gebhard D, Bergemann J
  
• (2010) Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis. Cell Commun Signal. 8:12
  Wolf SA, Bick-Sander A, Fabel K, Leal-Galicia P, Tauber S, Ramirez-Rodriguez G, Müller A, Melnik A, Waltinger TP, Ullrich O, Kempermann G
  
• (2010) Caveolin limits membrane microdomain mobility and integrin-mediated uptake of fibronectin-binding pathogens. J Cell Sci. 123(Pt 24):4280-91
  Hoffmann C, Berking A, Agerer F, Buntru A, Neske F, Chhatwal GS, Ohlsen K, Hauck CR
  
• (2010) Chlamydia pneumoniae-induced memory CD4+ T-cell activation in human peripheral blood correlates with distinct antibody response patterns. Clin Vaccine Immunol. 17(5):705-12
  Bunk S, Schaffert H, Schmid B, Goletz C, Zeller S, Borisova M, Kern F, Rupp J, Hermann C
  
• (2010) Cytokine-dependent balance of mitogenic effects in primary human lung fibroblasts related to cyclic AMP signaling and phosphodiesterase 4 inhibition. J Cell Physiol. 223(2):317-26
  Selige J, Tenor H, Hatzelmann A, Dunkern T
  
• (2010) Dysregulation of CD36 upon TLR-2 stimulation in monocytes from patients with atopic dermatitis and the TLR2 R753Q polymorphism. Exp Dermatol. 19(8):e296-8
  Niebuhr M, Langnickel J, Sigel S, Werfel T
  
• (2010) Ex vivo supplementation with nicotinic acid enhances cellular poly(ADP-ribosyl)ation and improves cell viability in human peripheral blood mononuclear cells. Biochem Pharmacol. 80(7):1103-12
  Weidele K, Kunzmann A, Schmitz M, Beneke S, Bürkle A
  
• (2010) Food for thought ... considerations and guidelines for basic test method descriptions in toxicology ALTEX. 27:309-17
  Leist M, Efremova L, Karreman C
  
• (2010) Inflammatory and age-related pathologies in mice with ectopic expression of human PARP-1. Mech Ageing Dev. 131(6):389-404
  Mangerich A, Herbach N, Hanf B, Fischbach A, Popp O, Moreno-Villanueva M, Bruns OT, Bürkle A
  
• (2010) Internalization and coreceptor expression are critical for TLR2-mediated recognition of lipoteichoic acid in human peripheral blood J Immunol. 185(6):3708-17
  Bunk S, Sigel S, Metzdorf D, Sharif O, Triantafilou K, Triantafilou M, Hartung T, Knapp S, von Aulock S
  
• (2010) Investigation of microcystin congener-dependent uptake into primary murine neurons Environ Health Perspect. 118(10):1370-5
  Feurstein D, Kleinteich K, Heussner AH, Stemmer K, Dietrich DR
  
• (2010) Malignant but not naïve hepatocytes of human and rodent origin are killed by TNF after metabolic depletion of ATP by fructose. J Hepatol. 53(5):896-902
  Speicher T, Foehrenbacher A, Pochic I, Weiland T, Wendel A
  
• (2010) Markers of murine embryonic and neural stem cells, neurons and astrocytes: reference points for developmental neurotoxicity testing. ALTEX. 27(1):17-42
  Kuegler PB, Zimmer B, Waldmann T, Baudis B, Ilmjärv S, Hescheler J, Gaughwin P, Brundin P, Mundy W, Bal-Price AK, Schrattenholz A, Krause KH, van Thriel C, Rao MS, Kadereit S, Leist M
  
• (2010) Regulation of liver regeneration by growth factors and cytokines. EMBO Mol Med. (8):294-305
  Böhm F, Köhler UA, Speicher T, Werner S
  
• (2010) The Center for Alternatives to Animal Testing - Europe (CAAT-EU): a transatlantic bridge for the paradigm shift in toxicology. ALTEX. 27(1):63-9
  Daneshian M, Leist M, Hartung T
  
• (2010) The role of organic anion transporting polypeptides (OATPs/SLCOs) in the toxicity of different microcystin congeners in vitro: a comparison of primary human hepatocytes and OATP-transfected HEK293 cells. Toxicol Appl Pharmacol. 245(1):9-20
  Fischer A, Hoeger SJ, Stemmer K, Feurstein D, Knobeloch D, Nussler A, Dietrich DR
  
• Apoptosis- and Bcl-2- Induced Alterations of the Nucleocytoplasmic Barrier, Konstanz, Univ., Diss., 2010
  Strasser, Christine
  
• Pathophysiological relevance of PDE inhibition in lung fibroblasts for the treatment of pulmonary diseases, Konstanz, Univ., Diss., 2010
  Selige, Jens
  
• Rolle der NOD-Rezeptoren für die intrazelluläre Immunerkennung von Chlamydophila pneumoniae und Charakterisierung der chlamydialen NOD-Liganden, Konstanz, Univ., Diss., 2010
  Erath, Sonja
  
• (2011) A framework program for the teaching of alternative methods (replacement, reduction, refinement) to animal experimentation. ALTEX. 28(4):341-52
  Daneshian M, Akbarsha MA, Blaauboer B, Caloni F, Cosson P, Curren R, Goldberg A, Gruber F, Ohl F, Pfaller W, van der Valk J, Vinardell P, Zurlo J, Hartung T, Leist M
  
• (2011) Assessment of chemical-induced impairment of human neurite outgrowth by multiparametric live cell imaging in high-density cultures. Toxicol Sci. 121(7):73- 87
  Stiegler NV, Krug AK, Matt F, Leist M
  
• (2011) Biomarker candidates of Chlamydophila pneumoniae proteins and protein fragments identified by affinity-proteomics using FTICR-MS and LC-MS/MS. J Am Soc Mass Spectrom. 22(4):784-8
  Susnea I, Bunk S, Wendel A, Hermann C, Przybylski M
  
• (2011) CD8- dendritic cells and macrophages cross-present poly(D,L-lactateco-glycolate) acid microsphere-encapsulated antigen in vivo. J. Immunol. 187(5):2112-21
  Schliehe C, Redaelli C, Engelhardt S, Fehlings M, Mueller M, van Rooijen N, Thiry M, Hildner K, Weller H, Groettrup M
  
• (2011) Cross-talk between TCR and CCR7 signaling sets a temporal threshold for enhanced T lymphocyte migration. J Immunol 187(11):5645-52
  Schaeuble K, Hauser MA, Singer E, Groettrup M, Legler DF
  
• (2011) Differential immunotoxicity of histone deacetylase inhibitors on malignant and naïve hepatocytes. Exp Toxicol Pathol. 63(5):511-7
  Weiller M, Weiland T, Dünstl G, Sack U, Künstle G, Wendel A
  
• (2011) Growth temperature-dependent expression of structural variants of Listeria monocytogenes lipoteichoic acid. Immunobiology. 216(1-2):24-31
  Dehus O, Pfitzenmaier M, Stuebs G, Fischer N, Schwaeble W, Morath S, Hartung T, Geyer A, Hermann C
  
• (2011) How to kill tumor cells with inhibitors of poly(ADP-ribosyl)ation. Int J Cancer. 128(2):251-65
  Mangerich A, Bürkle A
  
• (2011) Induced SYK knockout leads to suppressed allergic but not neutrophilic responses in mice. European Journal of Immunology 41(11):3208-18
  Wex EE, Bouyssou T, Duechs M, Erb KJ, Gantner F, Sanderson MP, Schnapp A, and Wollin L
  
• (2011) Microcystin congener- and concentration-dependent induction of murine neuron apoptosis and neurite degeneration. Toxicol Sci. 124(2):424-31
  Feurstein D, Stemmer K, Kleinteich J, Speicher T, Dietrich DR
  
• (2011) Microencapsulation of inorganic nanocrystals into PLGA microsphere vaccines enables their intracellular localization in dendritic cells by electron and fluorescence microscopy. J Control Release. 151(3):278-85
  Schliehe C, Schliehe C, Thiry M, Tromsdorf UI, Hentschel J, Weller H, Groettrup M
  
• (2011) Neisseria meningitidis has two independent modes of recognizing its human receptor CEACAM1. PloS One;6(1):e14609
  Kuespert K, Roth A, Hauck CR
  
• (2011) Neuroprotection by minocycline caused by direct and specific scavenging of peroxynitrite. J Biol Chem. 286(7):4991-5002
  Schildknecht S, Pape R, Müller N, Robotta M, Marquardt A, Bürkle A, Drescher M, Leist M
  
• (2011) Rapid, complete and large-scale generation of post-mitotic neurons from the human LUHMES cell line. J Neurochem. 119(5):957-71
  Scholz D, Pöltl D, Genewsky A, Weng M, Waldmann T, Schildknecht S, Leist M
  
• (2011) Rapid, complete and large-scale generation of post-mitotic neurons from the human LUHMES cell line. J Neurochem. 119(5):957-71
  Scholz D, Pöltl D, Genewsky A, Weng M, Waldmann T, Schildknecht S, Leist M
  
• (2011) Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration. Dev Cell. 20(3):397-404
  Kikuchi K, Holdway JE, Major RJ, Blum N, Dahn RD, Begemann G, Poss KD
  
• (2011) Sensitivity of dopaminergic neuron differentiation from stem cells to chronic low-dose methylmercury exposure Toxicol Sci. 121(2):357-67
  Zimmer B, Schildknecht S, Kuegler PB, Tanavde V, Kadereit S, Leist M
  
• (2011) Sensitivity of dopaminergic neuron differentiation from stem cells to chronic low-dose methylmercury exposure. Toxicol Sci. 121(2):357-67
  Zimmer B, Schildknecht S, Kuegler PB, Tanavde V, Kadereit S, Leist M
  
• (2011) The automated FADU-assay, a potential high-throughput in vitro method for early screening of DNA breakage. ALTEX 28(4):295-303
  Moreno-Villanueva M, Eltze T, Dressler D, Bernhardt J, Hirsch C, Wick P, von Scheven G, Lex K, Bürkle A
  
• (2011) The cannabinoid receptors agonist WIN55212-2 inhibits macrophageal differentiation and alters expression and phosphorylation of cell cycle control proteins. Cell Commun Signal. 9:33
  Paulsen K, Tauber S, Timm J, Goelz N, Dumrese C, Stolzing A, Hass R, Ullrich O
  
• (2011) The differential impact of PDE4 subtypes in human lung fibroblasts on cytokine-induced proliferation and myofibroblast conversion. J Cell Physiol. 226(8):1970-80
  Selige J, Hatzelmann A, Dunkern T
  
• (2011) TLR-agonist mediated suppression of allergic responses is associated with increased innate inflammation in the airways. Pulmonary pharmacology & therapeutics 24(2):203-14
  Duechs M, Hahn C, Benediktus E, Werner-Klein M, Braun A, Hoymann HG, Gantner F and Erb KJ
  
• (2011) TLR2 hypersensitivity of astrocytes as functional consequence of previous inflammatory episodes. J Immunol. 186(5):3237-47
  Henn A, Kirner S, Leist M
  
• Effects of Toll-like receptor agonists on the pathogenesis of atopic asthma in mice, Diss., Univ. Würzburg, 2011
  Düchs, Matthias
  
• Influence of different noxa on DNA repair capacity of primary human skin cells, Konstanz, Univ., Diss., 2011
  Burger, Katharina
  
• Integrin-mediated uptake of fibronectin-binding bacteria. (2011) Eur J Cell Biol. 90(11):891-6
  Hoffmann C, Ohlsen K, Hauck CR
  
• Modeling of neural differentiation by using embryonic stem cells to detect developmental toxicants, Konstanz, Univ., Diss., 2011
  Zimmer, Bastian
  
• Regulation of Alzheimer’s disease-relevant protein processing in human neurons of the LUHMES cell line, Konstanz, Univ., Diss., 2011
  Scholz, Diana
  
• Screen for kinases affecting amyloidogenic cleavage by BACE1, Konstanz, Univ., Diss., 2011
  Penzkofer, Stephan
  
• The role of antigen cross-presentation in the vaccine-induced activation of cytotoxic T-lymphocytes, Konstanz, Univ., Diss., 2011
  Schliehe, Christopher
  
• (2012) A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing - t4 report* ALTEX. 29(1):3-91
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• (2012) Adjuvant effects of different TLR agonists on the induction of allergen-specific Th2 responses. Open Journal of Immunology, Vol.2 No. 1
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• (2012) Apolipoprotein B100 is a suppressor of Staphylococcus aureus-induced innate immune responses in humans and mice. Eur J Immunol. 42(11):2983-9
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• (2012) Autocatalytic nitration of prostaglandin endoperoxide synthase-2 by nitrite inhibits prostanoid formation in rat alveolar macrophages. Antioxid Redox Signal. 17(10):1393-406
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• (2012) Characterization of mouse cell line IMA 2.1 as a potential model system to study astrocyte functions. ALTEX 29(3):261-74
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• (2012) Characterization of mouse cell line IMA 2.1 as a potential model system to study astrocyte functions. ALTEX. 29(3):261-74
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• (2012) Chromatin composition is changed by Poly(ADP-ribosyl)ation during chromatin immunoprecipitation. PLoS ONE 7(3):e32914
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• (2012) Compound selection for in vitro modeling of developmental neurotoxicity. Front Biosci (Landmark Ed). 17:2442-60
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• (2012) DNA damage in Nijmegen Breakage Syndrome cells leads to PARP hyperactivation and increased oxidative stress. PloS Genetics;8(3):e1002557
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• (2012) Epigenetic changes and disturbed neural development in a human embryonic stem cell-based model relating to the fetal valproate syndrome. Hum Mol Genet. 21(18):4104-14
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• (2012) Evaluation of developmental toxicants and signaling pathways in a functional test based on the migration of human neural crest cells. Environ Health Perspect. 120(8):1116-1122
  Zimmer B, Lee G, Balmer NV, Meganathan K, Sachinidis A, Studer L, Leist M
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• (2012) Extensive transcriptional regulation of chromatin modifiers during human neurodevelopment. PLoS One. 7(5):e36708
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• (2012) Fructose protects murine hepatocytes from tumor necrosis factor-induced apoptosis by modulating JNK signaling. J Biol Chem. 287(3):1837-46
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• (2012) GFAP- independent inflammatory competence and trophic functions of astrocytes generated from murine embryonic stem cells. Glia. 60(2):218-28
  Kuegler PB, Baumann BA, Zimmer B, Keller S, Marx A, Kadereit S, Leist M
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• (2012) HemITAM signaling by CEACAM3, a human granulocyte receptor recognizing bacterial pathogens. Arch Biochem Biophys. 524(1):77-83
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• (2012) In vivo screening of ligand-dependent hammerhead ribozymes. Methods Mol Biol. 848:455-63
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• (2012) Locally resolved membrane binding affinity of the N-terminus of α-synuclein. Biochemistry. 51(19):3960-2
  Robotta M, Hintze C, Schildknecht S, Zijlstra N, Jüngst C, Karreman C, Huber M, Leist M, Subramaniam V, Drescher M
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• (2012) Pleiotropic cellular functions of PARP1 in longevity and aging: genome maintenance meets inflammation. Oxid Med Cell Longev. 2012:321653
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• (2012) Posttranscriptional Boolean computation by combining aptazymes controlling mRNA translation initiation and tRNA activation. Mol Biosyst. 8(9):2242-8
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• (2012) Quantitative analysis of WRN exonuclease activity by isotope dilution mass spectrometry. Mech Ageing Dev. 133(8) 575-9
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• (2012) Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity. Cell Commun Signal. 10(1):1
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• (2012) Regulation of MMP-9 by a WIN-binding site in the monocyte-macrophage system independent from cannabinoid receptors. PLoS One. 7(11):e48272
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• (2012) Regulation of nuclear envelope permeability in cell death and survival. Nucleus. 3(6):540-51
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• (2012) Retinoic acid signaling controls the formation, proliferation and survival of the blastema during adult zebrafish fin regeneration. Development 139(1):107-16
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• (2012) Selective protection of human liver tissue in TNF-targeting of cancers of the liver by transient depletion of adenosine triphosphate. PLoS One. 7(12):e52496
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• (2012) Stable antigen is most effective for eliciting CD8+ T-cell responses after DNA vaccination and infection with recombinant vaccinia virus in vivo. J Virol. 86(18):9782-93
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• (2012) The proteomic analysis of endogenous FAT10 substrates identifies p62/SQSTM1 as a substrate of FAT10ylation. J Cell Sci. 125(Pt 19):4576-85
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• (2012) Ubiquitylation of the chemokine receptor CCR7 enables efficient receptor recycling and cell migration. J Cell Sci 125(Pt 19):4463-74
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• (2012) Uncoupling of ATP-depletion and cell death in human dopaminergic neurons. Neurotoxicology. 33(4):769-79
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• Improvement of animal models of COPD and identification of new therapeutic intervention principles therein, Konstanz, Univ., Diss., 2012
  Synwoldt, Peggy
  
• Raising cellular NAD+ levels in human cells by nicotinic acid supplementation: biological consequences related to PARP-1 mediated reactions, Konstanz, Univ., Diss., 2012
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• Regulation der Matrix-Metalloproteinase-9 durch das synthetische Cannabinoid WIN in Zellen des Monozyten-Makrophagen-Systems, Diss. Univ. Zürich, 2012
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• (2013) A 3-dimensional human embryonic stem cell (hESC)-derived model to detect developmental neurotoxicity of nanoparticles. Arch Toxicol. 87(4):721-33
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• (2013) Evidence for the detection of nonendotoxin pyrogens by the whole blood monocyte activation test. ALTEX. 30(2):169-208
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• (2013) Human embryonic stem cellderived test system for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol 87(1):123-43
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• (2013) Imaging of the DNA damage-induced dynamics of nuclear proteins via nonlinear photoperturbation. J Biophotonics 6(8):645-55
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• (2013) Innate Recognition by Neutrophil Granulocytes Differs between Neisseria gonorrhoeae Strains Causing Local or Disseminating Infections. Infect Immun. 81(7):2358-70
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• (2013) Mechanism of the antiproliferative activity of some naphthalene diimide g-quadruplex ligands. Mol Phamacol. 83(2):470-80
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• (2013) Oxidative and nitrative alpha-synuclein modifications and proteostatic stress: implications for disease mechanisms and interventions in synucleinopathies. J Neurochem. 125(4):491-511
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• (2013) Site-specific noncovalent interaction of the biopolymer Poly(ADP-ribose) with the Werner Syndrome Protein regulates protein functions.ACS Chem Biol. 8(1):179-88
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• (2013) The roles of endogenous retinoid signaling in organ and appendage regeneration. Cell Mol Life Sci. 70(20):3907-27
  Blum N, Begemann G
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• Developmental neurotoxicity and epigenetic changes in human model systems, Konstanz, Univ., Diss., 2013
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• Evaluation of new alternative strategies to predict neurotoxicity with human based test systems, Konstanz, Univ., Diss., 2013
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• Exploring bacterial binding to receptors of the CEACAM family as a basis for translational approaches, Konstanz, Univ., Diss., 2013
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• Roles and mechanisms of action of the NRF2 transcription factor in liver homeostasis and regeneration, Diss., Eidgenössische Technische Hochschule ETH Zürich, Nr. 21630, 2013
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• The role of the oncoprotein DEK in DNA replication stress and damage repair, Konstanz, Univ., Diss., 2013
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• (2014) A High-Fat Diet and NAD(+) Activate Sirt1 to Rescue Premature Aging in Cockayne Syndrome. Cell Metab. 20(5):840-55
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• (2014) Acrylamide alters neurotransmitter induced calcium responses in murine ESC-derived and primary neurons. Neurotoxicology. 43:117-26
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• (2014) Activated Nrf2 impairs liver regeneration in mice by activation of genes involved in cell-cycle control and apoptosis. Hepatology. 60(2):670-8
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• (2014) Alpha-Synuclein Binds to the Inner Membrane of Mitochondria in an α-Helical Conformation. Chembiochem. Nov 24;15(17):2499-502
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• (2014) CCR7: roles in cancer cell dissemination, migration and metastasis formation. Int J Biochem Cell Biol. 54:78-82
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• (2014) Consensus report on the future of animal-free systemic toxicity testing. ALTEX. 31(3):341-56
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• (2014) Current approaches and future role of high content imaging in safety sciences and drug discovery. ALTEX. 31(4):479-93
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• (2014) Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 27(3):408-20
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• (2014) Development of a novel severe triple allergen asthma model in mice which is resistant to dexamethasone and partially resistant to TLR7 and TLR9 agonist treatment. PLoS One. 9(3):e91223
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• (2014) Epigenetics and transcriptomics to detect adverse drug effects in model systems of human development. Basic Clin Pharmacol Toxicol. 115(1):59-68
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• (2014) Ex vivo culture of intestinal crypt organoids as a model system for assessing cell death induction in intestinal epithelial cells and enteropathy. Cell Death Dis. 5:e1228
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• (2014) From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 88(7):1451-68
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• (2014) Impairment of glutamate signaling in mouse central nervous system neurons in vitro by tri-ortho-cresyl phosphate at noncytotoxic concentrations. Toxicol Sci. 142(1):274-84
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• (2014) iPS cell derived neuronal cells for drug discovery. Trends Pharmacol Sci. Oct;35(10):510-9
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• (2014) Mitochondrial DNA copy number - but not a mitochondrial tandem CC to TT transition - is increased in sun-exposed skin. Exp Dermatol. Mar;23(3):209-11
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• (2014) Profiling of drugs and environmental chemicals for functional impairment of neural crest migration in a novel stem cell-based test battery. Arch Toxicol. 88(5):1109-26
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• Development of neuron-astrocyte co-culture system for mechanistic and pharmacological studies in neurodegeneration, Konstanz, Univ., Diss., 2015
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• Identification of novel interaction partners of the chemokine receptor CCR7 involved in cancer and immune cell migration, Konstanz, Univ., Diss., 2015
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• Immunotherapy of Prostate Carcinoma with biodegradable PLGA Microspheres, Konstanz, Univ., Diss., 2015
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• RNA Synthetic Biology using the Hammerhead Ribozyme: Engineering of Artificial Genetic Switches, Konstanz, Univ., Diss., 2015
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