Staab, Julia F.

[["dc.contributor.author","Nast, Roswitha"],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Meyer, Thomas"],["dc.contributor.editor","Behzadi, Payam"],["dc.date.accessioned","2019-08-07T07:32:36Z"],["dc.date.available","2019-08-07T07:32:36Z"],["dc.date.issued","2019"],["dc.description.abstract","Signal transducers and activators of transcription (STATs) are a family of cytokine-regulated transcription factors, which serve the dual role of external signal transduction and transcriptional activation. The founding member of this family, STAT1, is involved in a plethora of cellular processes, including interferon-dependent upregulation of various effector mechanisms in immune and non-immune cells to control bacterial, fungal and parasitic infections. In this chapter, we discuss the principles of STAT1-driven gene expression and focus on the clinical phenotypes of various human STAT1 mutations. In particular, we highlight the significance of sequence-specific DNA binding and intact nucleocytoplasmic shuttling for full transcriptional activation of interferon-driven target genes."],["dc.identifier.doi","10.5772/intechopen.82699"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62332"],["dc.language.iso","en"],["dc.notes.status","zu prüfen"],["dc.relation.isbn","978-1-78985-683-5"],["dc.relation.isbn","978-1-78985-684-2"],["dc.relation.ispartof","Gene Regulation"],["dc.title","Gene Activation by the Cytokine-Driven Transcription Factor STAT1"],["dc.type","book_chapter"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","A143"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Psychosomatic Medicine"],["dc.bibliographiccitation.lastpage","A144"],["dc.bibliographiccitation.volume","78"],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Herrmann-Lingen, Christoph"],["dc.contributor.author","Meyer, Thomas"],["dc.date.accessioned","2018-11-07T10:15:43Z"],["dc.date.available","2018-11-07T10:15:43Z"],["dc.date.issued","2016"],["dc.identifier.isi","000373949800470"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40870"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.publisher.place","Philadelphia"],["dc.relation.conference","74th Annual Meeting of the American-Psychosomatic-Society"],["dc.relation.eventlocation","Denver, CO"],["dc.relation.issn","1534-7796"],["dc.relation.issn","0033-3174"],["dc.title","SITE-DIRECTED MUTAGENESIS OF STAT1 TRANSCRIPTION FACTOR IN THE STUDY OF INTERFERON-INDUCED DEPRESSION"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","108"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","ZEITSCHRIFT FUR PSYCHOSOMATISCHE MEDIZIN UND PSYCHOTHERAPIE"],["dc.bibliographiccitation.lastpage","109"],["dc.bibliographiccitation.volume","63"],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Meyer, Thomas"],["dc.date.accessioned","2018-11-07T10:28:51Z"],["dc.date.available","2018-11-07T10:28:51Z"],["dc.date.issued","2017"],["dc.identifier.isi","000396100900075"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43515"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Vandenhoeck & Ruprecht"],["dc.publisher.place","Gottingen"],["dc.relation.issn","2196-8349"],["dc.relation.issn","1438-3608"],["dc.title","Mechanisms of depressive Stress Responses in response to Interferon Administration: Mutagenesis of the Transcription Factor STAT1 in the Study of Interferon-induced Depression"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","234"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Gene"],["dc.bibliographiccitation.lastpage","238"],["dc.bibliographiccitation.volume","586"],["dc.contributor.author","Kobbe, Robin"],["dc.contributor.author","Kolster, Manuela"],["dc.contributor.author","Fuchs, Sebastian"],["dc.contributor.author","Schulze-Sturm, Ulf"],["dc.contributor.author","Jenderny, Jutta"],["dc.contributor.author","Kochhan, Lothar"],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Tolosa, Eva"],["dc.contributor.author","Grimbacher, Bodo"],["dc.contributor.author","Meyer, Thomas"],["dc.date.accessioned","2018-11-07T10:11:30Z"],["dc.date.available","2018-11-07T10:11:30Z"],["dc.date.issued","2016"],["dc.description.abstract","Recently, gain-of-function (GOF) mutations in the gene encoding signal transducer and activator of transcription 1 (STAT1) have been associated with chronic mucocutaneous candidiasis (CMC). This case report describes a 10-year-old boy presenting with signs of common variable immunodeficiency (CVID), failure to thrive, impaired neurological development, and a history of recurrent mucocutaneous Candida infections. Sequencing of the STAT1 gene identified a heterozygous missense mutation in exon 7 encoding the STAT1 coiled-coil domain (c.514T>C, p.Phe172Leu). In addition to hypogammaglobulinemia with B-cell deficiency, and a low percentage of Th17 cells, immunological analysis of the patient revealed a marked depletion of forkhead-box P3(+)-expressing regulatory T cells (Tregs). In vitro stimulation of T cells from the patient with interferon-alpha (IFN alpha) and/or IFN gamma resulted in a significantly increased expression of STAT1-regulated target genes such as MIG1, IRF1, MX1, MCP1/CCL2, IFI-56K, and CXCL10 as compared to IFN-treated cells from a healthy control, while no IFN alpha/gamma-mediated up-regulation of the FOXP3 gene was found. These data demonstrate that the STAT1 GOF mutation F172L, which results in impaired stability of the antiparallel STAT1 dimer conformation, is associated with inhibited Treg cell development and neurological symptoms. (C) 2016 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.gene.2016.04.006"],["dc.identifier.isi","000376696100006"],["dc.identifier.pmid","27063510"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40059"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","1879-0038"],["dc.relation.issn","0378-1119"],["dc.title","Common variable immunodeficiency, impaired neurological development and reduced numbers of T regulatory cells in a 10-year-old boy with a STAT1 gain-of-function mutation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","596"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Molecular Immunology"],["dc.bibliographiccitation.lastpage","606"],["dc.bibliographiccitation.volume","67"],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Riebeling, Theresa"],["dc.contributor.author","Koch, Verena"],["dc.contributor.author","Herrmann-Lingen, Christoph"],["dc.contributor.author","Meyer, Thomas"],["dc.date.accessioned","2018-11-07T09:51:03Z"],["dc.date.available","2018-11-07T09:51:03Z"],["dc.date.issued","2015"],["dc.description.abstract","Defective cooperative DNA binding of STAT1 (signal transducer and activator of transcription 1) transcription factor has impact on interferon-gamma(IFN gamma)-regulated transcriptional responses. In this study, we generated N-terminal gain-of-function mutants of this protein which exhibited hyperactive cooperativity and assessed their functional consequences on gene expression. Our data show that four negatively charged, surface-exposed amino acid residues in the N-terminal domain dimer are engaged in the disassembly of tyrosine-phosphorylated tetrameric complexes on DNA and prevent the occurrence of higher-order STAT1 oligomers on low-affinity DNA binding sites. Owing to their improved tetramer stability, the N-terminal mutants showed relaxed sequence requirements for the binding to DNA as compared to the wild-type protein. Similarly to a STAT1 mutant with impaired tetramerization, the N-terminal gain-of-function mutants showed elevated tyrosine-phosphorylation levels and prolonged nuclear accumulation upon stimulation of cells with IFN gamma. However, in contrast to the global impairment of IFN gamma signalling in tetramerization-deficient mutants, the transcriptional consequences of the N-terminal gain-of-function mutants are rather distinct and affect gene expression locally in a promoter-specific manner. Thus, we conclude that the STAT1 N-domain acts as a double-edged sword: while one interface is crucial for the formation of tetrameric complexes on IFN gamma-regulated promoters, the opposite interface harbours an inhibitory mechanism that limits the accumulation of higher-order oligomers simply by disrupting cooperative DNA binding. (C) 2015 Published by Elsevier Ltd."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft (DFG) [1816]; DFG"],["dc.identifier.doi","10.1016/j.molimm.2015.07.015"],["dc.identifier.isi","000361922400045"],["dc.identifier.pmid","26275341"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35836"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","0161-5890"],["dc.title","The two interfaces of the STAT1 N-terminus exhibit opposite functions in IFN gamma-regulated gene expression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e12887"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Cellular Microbiology"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Nast, Roswitha"],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Meyer, Thomas"],["dc.contributor.author","Lüder, Carsten G. K."],["dc.date.accessioned","2019-08-07T07:16:19Z"],["dc.date.available","2019-08-07T07:16:19Z"],["dc.date.issued","2018"],["dc.description.abstract","Toxoplasma gondii is an obligate intracellular parasite that infects up to 30% of humans worldwide. It can lead to severe diseases particularly in individuals with immature or defective immune responses. Control of T. gondii relies on the IFN-γ-induced signal transducer and activator of transcription-1 (STAT1) pathway. T. gondii, however, largely inactivates STAT1-mediated gene transcription by T. gondii inhibitor of STAT1-dependent transcription (TgIST), a parasite effector protein binding to STAT1. Here, we have analysed requirements of STAT1 to bind TgIST and characterised downstream effects on STAT1 signalling. TgIST bound to STAT1 dimers but more efficiently assembled with STAT1 tetramers, which are essential for effective IFN-γ responsiveness. Such binding was abrogated in N-terminal, but not C-terminal deletion mutants of STAT1. Furthermore, TgIST did not bind to the STAT1F77A substitution mutant that cannot form STAT1 tetramers, resulting in a complete unresponsiveness of parasite-infected STAT1F77A -expressing cells to IFN-γ. Remarkably, binding of TgIST considerably increased the affinity of the aberrant STAT1 tetramers for DNA consensus sequence binding motifs and even enabled binding to nonconsensus sequences. Consistent with the increased DNA binding, STAT1 from parasite-infected cells remained phosphorylated at Tyr701 and Ser727 and was retained within the nucleus in a DNA-bound state. The sustained and promiscuous binding activity particularly of STAT1 tetramers to unspecific DNA sites lacking a consensus STAT1-binding motif is an as yet unrecognised mechanism contributing to the defective IFN-γ-mediated signalling in T. gondii-infected cells."],["dc.identifier.doi","10.1111/cmi.12887"],["dc.identifier.pmid","29968354"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62329"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1462-5822"],["dc.relation.issn","1462-5814"],["dc.title","Toxoplasma gondii stabilises tetrameric complexes of tyrosine-phosphorylated signal transducer and activator of transcription-1 and leads to its sustained and promiscuous DNA binding"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","141"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Endocrine Pathology"],["dc.bibliographiccitation.lastpage","150"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Barth, Peter J."],["dc.contributor.author","Meyer, Thomas"],["dc.date.accessioned","2018-11-07T09:06:55Z"],["dc.date.available","2018-11-07T09:06:55Z"],["dc.date.issued","2012"],["dc.description.abstract","Expression of cytokine-regulated signal transducer and activator of transcription (STAT) proteins was histochemically assessed in patients diagnosed as having Hashimoto's disease or focal lymphocytic thyroiditis (n = 10). All surgical specimens showed histological features of lymphocytic thyroiditis, including a diffuse infiltration with mononuclear cells and an incomplete loss of thyroid follicles, resulting in the destruction of glandular tissue architecture. Immunohistochemical analysis demonstrated differential expression patterns of the various members of the STAT transcription factors examined, indicating that each member of this conserved protein family has its distinct functions in the development of the disease. Using an antibody that specifically recognized the phosphorylated tyrosine residue in position 701, we detected activated STAT1 dimers in numerous germinal macrophages and infiltrating lymphocytes as well as in oncocytes. In contrast, STAT3 expression was restricted to epithelial cells and showed a clear colocalization with the antiapoptotic protein Bcl-2. Moreover, expression of phospho-STAT3 was associated with low levels of stromal fibrosis, suggesting that STAT3 serves as a protective factor in the remodeling of the inflamed thyroid gland. Phospho-STAT5 immunoreactivity was detected in numerous infiltrating cells of hematopoietic origin and, additionally, in hyperplastic follicular epithelia. This tissue distribution demonstrated that activated STAT5 molecules participate in both lymphocytopoiesis and possibly also in the buildup of regenerating thyroid follicles. Taken together, the cell-type-specific expression patterns of STAT proteins in human lymphocytic thyroiditis reflect their distinct and partially antagonistic roles in orchestrating the balance between degenerating and regenerating processes within a changing cytokine environment."],["dc.identifier.doi","10.1007/s12022-012-9204-0"],["dc.identifier.isi","000307518400002"],["dc.identifier.pmid","22527947"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25663"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Humana Press Inc"],["dc.relation.issn","1046-3976"],["dc.title","Cell-Type-Specific Expression of STAT Transcription Factors in Tissue Samples from Patients with Lymphocytic Thyroiditis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","631"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Biochemical Genetics"],["dc.bibliographiccitation.lastpage","648"],["dc.bibliographiccitation.volume","58"],["dc.contributor.author","Meyer, Thomas"],["dc.contributor.author","Rothe, Isabel"],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Deter, Hans-Christian"],["dc.contributor.author","Fangauf, Stella V."],["dc.contributor.author","Hamacher, Stefanie"],["dc.contributor.author","Hellmich, Martin"],["dc.contributor.author","Jünger, Jana"],["dc.contributor.author","Ladwig, Karl-Heinz"],["dc.contributor.author","Michal, Matthias"],["dc.contributor.author","Petrowski, Katja"],["dc.contributor.author","Ronel, Joram"],["dc.contributor.author","Söllner, Wolfgang"],["dc.contributor.author","Weber, Cora"],["dc.contributor.author","de Zwaan, Martina"],["dc.contributor.author","Williams, Redford B."],["dc.contributor.author","Albus, Christian"],["dc.contributor.author","Herrmann-Lingen, Christoph"],["dc.date.accessioned","2020-12-10T14:11:22Z"],["dc.date.available","2020-12-10T14:11:22Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1007/s10528-020-09967-w"],["dc.identifier.eissn","1573-4927"],["dc.identifier.issn","0006-2928"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/71058"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Length Polymorphisms in the Angiotensin I-Converting Enzyme Gene and the Serotonin-Transporter-Linked Polymorphic Region Constitute a Risk Haplotype for Depression in Patients with Coronary Artery Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Neuroimmunomodulation"],["dc.bibliographiccitation.lastpage","10"],["dc.contributor.author","Veiz, Elisabeth"],["dc.contributor.author","Kieslich, Susann-Kristin"],["dc.contributor.author","Czesnik, Dirk"],["dc.contributor.author","Herrmann‐Lingen, Christoph"],["dc.contributor.author","Meyer, Thomas J."],["dc.contributor.author","Staab, Julia"],["dc.date.accessioned","2022-06-01T09:39:38Z"],["dc.date.available","2022-06-01T09:39:38Z"],["dc.date.issued","2022"],["dc.description.abstract","The vagus nerve constitutes the main component of the parasympathetic nervous system and plays an important role in the regulation of neuro-immune responses. Invasive stimulation of the vagus nerve produces anti-inflammatory effects; however, data on humoral immune responses of transcutaneous vagus nerve stimulation (tVNS) are rare. Therefore, the present study investigated changes in serum cytokine concentrations of interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor α (TNFα) following a short-term, non-invasive stimulation of the vagus nerve. <b><i>Methods:</i></b> Whole blood samples were collected before and after a short-lived application of active tVNS at the inner tragus as well as sham stimulation of the earlobe. Cytokine serum concentrations were determined in two healthy cohorts of younger (<i>n</i> = 20) and older participants (<i>n</i> = 19). Differences between active and sham conditions were analyzed using linear mixed models and post hoc <i>F</i> tests after applying Yeo-Johnson power transformations. This trial was part of a larger study registered on ClinicalTrials.gov (NCT05007743). <b><i>Results:</i></b> In the young cohort, IL-6 and IL-1β concentrations were significantly increased after active stimulation, whereas they were slightly decreased after sham stimulation (IL-6: <i>p</i> = 0.012; IL-1β: <i>p</i> = 0.012). Likewise, in the older cohort, IL-1β and IL-8 concentrations were significantly elevated after active stimulation and reduced after sham application (IL-8: <i>p</i> = 0.007; IL-1β: <i>p</i> = 0.001). In contrast, circulating TNFα concentrations did not change significantly in either group. <b><i>Conclusion:</i></b> Our results show that active tVNS led to an immediate increase in the serum concentrations of certain pro-inflammatory cytokines such as IL-1β, IL-6, and/or IL-8 in two independent cohorts of healthy study participants."],["dc.identifier.doi","10.1159/000524646"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/108524"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-572"],["dc.relation.eissn","1423-0216"],["dc.relation.issn","1021-7401"],["dc.relation.orgunit","Abteilung Klinische Psychologie und Psychotherapie"],["dc.relation.orgunit","Klinik für Neurologie"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.title","Increased Concentrations of Circulating Interleukins following Non-Invasive Vagus Nerve Stimulation: Results from a Randomized, Sham-Controlled, Crossover Study in Healthy Subjects"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","79"],["dc.bibliographiccitation.journal","Molecular Immunology"],["dc.bibliographiccitation.lastpage","88"],["dc.bibliographiccitation.volume","128"],["dc.contributor.author","Staab, Julia"],["dc.contributor.author","Schwämmle, Till"],["dc.contributor.author","Meyer, Thomas"],["dc.date.accessioned","2021-04-14T08:28:54Z"],["dc.date.available","2021-04-14T08:28:54Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1016/j.molimm.2020.10.005"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82738"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.issn","0161-5890"],["dc.title","The pathogenic T387A missense mutation in the gene encoding signal transducer and activator of transcription 1 exhibits a differential gene expression profile"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]