Dittmann, Kai

[["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","The Journal of Immunology"],["dc.bibliographiccitation.volume","183"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T11:25:03Z"],["dc.date.available","2018-11-07T11:25:03Z"],["dc.date.issued","2009"],["dc.format.extent","2891"],["dc.identifier.doi","10.4049/jimmunol.0990063"],["dc.identifier.isi","000269391400001"],["dc.identifier.pmid","19696426"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56544"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Immunologists"],["dc.relation.issn","0022-1767"],["dc.title","Comment on \"Direct Hematological Toxicity and Illegitimate Chromosomal Recombination Caused by the Systemic Activation of CreER(T2)\""],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.subtype","letter_note"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","19614"],["dc.bibliographiccitation.issue","32"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","19628"],["dc.bibliographiccitation.volume","290"],["dc.contributor.author","Linder, Benedikt"],["dc.contributor.author","Weber, Susanne"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Adamski, Jerzy"],["dc.contributor.author","Hahn, Heidi"],["dc.contributor.author","Uhmann, Anja"],["dc.date.accessioned","2018-11-07T09:53:20Z"],["dc.date.available","2018-11-07T09:53:20Z"],["dc.date.issued","2015"],["dc.description.abstract","The Patched1 (Ptch)-mediated inhibition of Smoothened (Smo) is still an open question. However, a direct Ptch/Smo interaction has been excluded, Smo modulators were identified, but the endogenous signal transmitting molecule remains undiscovered. Here, we demonstrate that calcitriol, the hormonally active form of vitamin D-3, is an excellent candidate for transmission of Ptch/Smo interaction. Our study reveals that Ptch expression is sufficient to release calcitriol from the cell and that calcitriol inhibits Smo action and ciliary translocation by acting on a site distinct from the 7-transmembrane domain or the cysteine-rich domain. Moreover calcitriol strongly synergizes with itraconazole (ITZ) in Smo inhibition, which did not result from elevated calcitriol bioavailability due to ITZ-mediated 24-hydroxylase inhibition but rather from a direct interaction of the compounds at the level of Smo. Together, we suggest that calcitriol represents a possible endogenous transmitter of Ptch/Smo interaction. Moreover calcitriol or calcitriol derivatives combined with ITZ might be a treatment option of Hedgehog-associated cancers."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [UH 228/2-1, UH228/2-2]"],["dc.identifier.doi","10.1074/jbc.M115.646141"],["dc.identifier.isi","000359364600023"],["dc.identifier.pmid","26126827"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36311"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","1083-351X"],["dc.relation.issn","0021-9258"],["dc.title","A Functional and Putative Physiological Role of Calcitriol in Patched1/Smoothened Interaction"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","134"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Gastroenterology"],["dc.bibliographiccitation.lastpage","U256"],["dc.bibliographiccitation.volume","144"],["dc.contributor.author","Pelczar, Penelope"],["dc.contributor.author","Zibat, Arne"],["dc.contributor.author","van Dop, Willemijn A."],["dc.contributor.author","Heijmans, Jarom"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Gruber, Wolfgang"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Guijarro, Maria V."],["dc.contributor.author","Hernando, Eva"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Wojnowski, Leszek"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Taguchi, Takahiro"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Hogendoorn, Pancras Cornelis Wilhelmus"],["dc.contributor.author","Antonescu, Cristina R."],["dc.contributor.author","Rubin, Brian P."],["dc.contributor.author","Schulz-Schaeffer, Walter Joachim"],["dc.contributor.author","Aberger, Fritz"],["dc.contributor.author","van den Brink, Gijs R."],["dc.contributor.author","Hahn, Heidi Eva"],["dc.date.accessioned","2018-11-07T09:30:42Z"],["dc.date.available","2018-11-07T09:30:42Z"],["dc.date.issued","2013"],["dc.description.abstract","BACKGROUND & AIMS: A fraction of gastrointestinal stromal tumor (GIST) cells overexpress the platelet-derived growth factor receptor (PDGFR) A, although most overexpress KIT. It is not known if this is because these receptor tyrosine kinases have complementary oncogenic potential, or because of heterogeneity in the cellular origin of GIST. Little also is known about why Hedgehog (HH) signaling is activated in some GIST. HH binds to and inactivates the receptor protein patched homolog (PTCH). METHODS: Ptch was conditionally inactivated in mice (to achieve constitutive HH signaling) using a Cre recombinase regulated by the lysozyme M promoter. Cre-expressing cells were traced using R26R-LacZ reporter mice. Tumors were characterized by in situ hybridization, immunohistochemistry, immunoblot, and quantitative reverse-transcriptase polymerase chain reaction analyses. Cell transformation was assessed by soft agar assay. RESULTS: Loss of Ptch from lysozyme M-expressing cells resulted in the development of tumors of GIST-like localization and histology; these were reduced when mice were given imatinib, a drug that targets KIT and PDGFRA. The Hh signaling pathway was activated in the tumor cells, and Pdgfr alpha, but not Kit, was overexpressed and activated. Lineage tracing revealed that Cre-expressing intestinal cells were Kit-negative. These cells sometimes expressed Pdgfr alpha and were located near Kit-positive interstitial cells of Cajal. In contrast to KIT, activation of PDGFRA increased anchorage-independent proliferation and was required for tumor formation in mice by cells with activated HH signaling. CONCLUSIONS: Inactivation of Ptch in mice leads to formation of GIST-like tumors that express Pdgfr alpha, but not Kit. Activation of Pdgfr alpha signaling appears to facilitate tumorigenesis."],["dc.identifier.doi","10.1053/j.gastro.2012.09.061"],["dc.identifier.isi","000312965100034"],["dc.identifier.pmid","23041331"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31367"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","W B Saunders Co-elsevier Inc"],["dc.relation.issn","0016-5085"],["dc.title","Inactivation of Patched1 in Mice Leads to Development of Gastrointestinal Stromal-Like Tumors That Express Pdgfr alpha but Not Kit"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2620"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Journal of Investigative Dermatology"],["dc.bibliographiccitation.lastpage","2629"],["dc.bibliographiccitation.volume","134"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Hess, Ina"],["dc.contributor.author","Frommhold, Anke"],["dc.contributor.author","Koenig, Simone"],["dc.contributor.author","Zabel, Sebastian"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Reifenberger, Julia"],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T09:34:46Z"],["dc.date.available","2018-11-07T09:34:46Z"],["dc.date.issued","2014"],["dc.description.abstract","The development of basal cell carcinoma (BCC), the most frequently diagnosed tumor among persons with European ancestry, is closely linked to mutations in the Hedgehog (Hh) receptor and tumor suppressor Patched1 (Ptch). Using Ptch(flox/flox)CD4Cre(+/-) mice, in which Ptch was ablated in CD4Cre-expressing cells, we demonstrate that the targeted cells can give rise to BCC after treatment with DMBA (7,12-dimethylbenz(a)anthracene)/TPA (12-O-tetradecanoylphorbol-13-acetate), but not after wounding of the skin. In addition, in this model, BCC are not caused by malfunctioning of Ptch-deficient T cells, as BCC did not develop when bone marrow (BM) of Ptch(flox/flox)CD4Cre(+/-) mice was transplanted into Ptch wild-type mice. Instead, lineage-tracing experiments and flow cytometric analyses suggest that the tumors are initiated from rare Ptch-deficient stem cell-like cells of the epidermis that express CD4. As DMBA/TPA is a prerequisite for BCC development in this model, the initiated cells need a second stimulus for expansion and tumor formation. However, in contrast to papilloma, this stimulus seems to be unrelated to alterations in the Ras signaling cascade. Together, these data suggest that biallelic loss of Ptch in CD4(+) cells does not suffice for BCC formation and that BCC formation requires a second so far unknown event, at least in the Ptch(flox/flox)CD4Cre(+/-) BCC mouse model."],["dc.identifier.doi","10.1038/jid.2014.157"],["dc.identifier.isi","000342200400023"],["dc.identifier.pmid","24662765"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32249"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","1523-1747"],["dc.relation.issn","0022-202X"],["dc.title","DMBA/TPA Treatment Is Necessary for BCC Formation from Patched Deficient Epidermal Cells in Ptch(flox/flox)CD4Cre(+/-) Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","831"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Arthritis & Rheumatology"],["dc.bibliographiccitation.lastpage","840"],["dc.bibliographiccitation.volume","66"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Wuelling, Manuela"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Hahn, Heidi"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Vortkamp, Andrea"],["dc.contributor.author","Wienands, Juergen"],["dc.date.accessioned","2018-11-07T09:41:33Z"],["dc.date.available","2018-11-07T09:41:33Z"],["dc.date.issued","2014"],["dc.description.abstract","Objective. During development of the vertebrate skeleton, chondrocytes form a cartilage template that is gradually replaced by bone. Hormones of the Hedgehog (HH) family have been implicated in the ossification process, but their exact relationship to normal or pathogenic bone formation is unclear. This study was undertaken to establish a genetic tool that allows the discrete inactivation of genes in spinal chondrocytes, and to investigate in vivo how chondrocyte-specific ablation of the inhibitory HH receptor Patched 1 (Ptch1) affects skeleton integrity. Methods. A Cre-deleter mouse strain, mb1-Cre, for selective gene recombination in spinal chondrocytes was identified by in situ hybridization and histologic analysis. The mb1-Cre(+/-) animals were crossed with mice that harbor a loxP-flanked Ptch1 gene (Ptch1(flox/flox)) to abrogate the inhibition of the HH signaling pathway in chondrocytes. The skeletal integrity of F1 mice was characterized by high-resolution flat-panel-based volume computed tomography and histologic staining procedures. Results. During the first weeks after birth, all mb1-Cre(+/-)/Ptch1(flox/flox) mice developed progressive spinal fusion with malformation of the vertebrae. This phenotype was caused by aberrant chondrocyte proliferation in the intervertebral discs that blocked endochondral ossification. Importantly, the disease pattern occurred in an inflammation-independent manner. Conclusion. Our findings indicate that chronic activation of the HH signal pathway in spinal chondrocytes can trigger an ankylosing spine morphology without immune cell contributions. Hence, the destruction of cartilage and loss of axial joint integrity can result from chondrocyte-intrinsic defects of monogenic origin."],["dc.description.sponsorship","DFG [TRR130]"],["dc.identifier.doi","10.1002/art.38325"],["dc.identifier.isi","000337361000009"],["dc.identifier.pmid","24757136"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33760"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","2326-5205"],["dc.relation.issn","2326-5191"],["dc.title","Inactivation of Patched1 in Murine Chondrocytes Causes Spinal Fusion Without Inflammation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1814"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Blood"],["dc.bibliographiccitation.lastpage","1823"],["dc.bibliographiccitation.volume","110"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Koleva, Milena"],["dc.contributor.author","Frommhold, Anke"],["dc.contributor.author","Zibat, Arne"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Adham, Ibrahim M."],["dc.contributor.author","Nitsche, Mirko"],["dc.contributor.author","Heller, Tanja"],["dc.contributor.author","Armstrong, Victor"],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T10:58:34Z"],["dc.date.available","2018-11-07T10:58:34Z"],["dc.date.issued","2007"],["dc.description.abstract","A first step in hematopoiesis is the specification of the lymphoid and myeloid lineages from multipotent progenitor cells in the bone marrow. Using a conditional ablation strategy in adult mice, we show that this differentiation step requires Patched (Ptch), the cell surface-bound receptor for Hedgehog (Hh). In the absence of Ptch, the development of T- and B-lymphoid lineages is blocked at the level of the common lymphoid progenitor in the bone marrow. Consequently, the generation of peripheral T and B cells is abrogated. Cells of the myeloid lineage develop normally in Ptch mutant mice. Finally, adoptive transfer experiments identified the stromal cell compartment as a critical Ptch-dependent inducer of lymphoid versus myeloid lineage commitment. Our data show that Ptch acts as a master switch for proper diversification of hematopoietic stem cells in the adult organism."],["dc.identifier.doi","10.1182/blood-2007-02-075648"],["dc.identifier.isi","000249671700022"],["dc.identifier.pmid","17536012"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50494"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Hematology"],["dc.relation.issn","0006-4971"],["dc.title","The Hedgehog receptor Patched controls lymphoid lineage commitment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3383"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","The Journal of Immunology"],["dc.bibliographiccitation.lastpage","3391"],["dc.bibliographiccitation.volume","186"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Hess, Ina"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Fassnacht, Martin"],["dc.contributor.author","Bhandoola, Avinash"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2018-11-07T08:58:08Z"],["dc.date.available","2018-11-07T08:58:08Z"],["dc.date.issued","2011"],["dc.description.abstract","We recently described that T cell specification in mice deficient in the Hedgehog (Hh) receptor Patched (Ptch) is blocked at the level of the common lymphoid progenitor in the bone marrow (BM). Adoptive transfer of wild-type BM in Ptch-deficient mice provides evidence that T cell development strictly depends on Ptch expression in the nonhematopoietic compartment. Transplantation experiments using BM deficient in the glucocorticoid receptor exclude any involvement of the stress hormone corticosterone in our model. Using cell-type-specific knockout mice, we show that T cell development is independent of T cell-intrinsic Ptch expression. Furthermore, Ptch expression by the thymus stroma is dispensable, as revealed by fetal thymus organ culture and thymus transplantation. In contrast, analysis of the earliest thymic progenitors in Ptch-deficient mice indicated that Ptch is required for the development or supply of thymic homing progenitors that give rise to earliest thymic progenitors. Collectively, our findings identified Ptch as an exclusive T cell-extrinsic factor necessary for proper development of T cells at their prethymic stage. This observation may be important for current considerations using Hh inhibitors upstream of Ptch in diseases accompanied by aberrant Hh signaling. The Journal of Immunology, 2011, 186: 3383-3391."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [HA 2197/6-1, RE 1631/8-1]"],["dc.identifier.doi","10.4049/jimmunol.1001939"],["dc.identifier.isi","000287923500014"],["dc.identifier.pmid","21317383"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23570"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Immunologists"],["dc.relation.issn","0022-1767"],["dc.title","T Cell Development Critically Depends on Prethymic Stromal Patched Expression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]