Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 56 for “"NOTCH1"”.
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Ikkalpha Mediated Notch1 Activation Promotes Tumorigenesis Via Foxa2 Suppression
… of IKKa, pFOXA2 (S107/ 111), and activated NOTCH1 were significantly higher in hepatocellular carcinoma tumors than in normal liver tissues and that pFOXA2 (S107/111) expression was positively correlated with IKKa and activated NOTCH1 expression in tumor tissues. Therefore, dysregulation of …
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Untersuchung zur Rolle von Notch1 in T-Zellentwicklung und Lymphomgenese
… Organen gezeigt werden. Insbesondere unterdrückt Notch1 nach Ligandenbindung die Bildung von B-Zellen im Thymus und fördert stattdessen die Entwicklung von T-Zellen. Durch Aktivierung der γ-Sekretase wird die intrazelluläre Domäne von Notch1 freigesetzt und transloziert in den Kern. Dort wirkt …
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The Role of Notch1 in Adult Hippocampal Neurogenesis and Function
… underlying mechanisms are still poorly defined. Notch1 is a master regulator of developmental neurogenesis, yet its role in adult hippocampal neurogenesis is unclear. To test the hypothesis that cell-intrinsic Notch1 is critical to both basal and exercise-induced SGZ neurogenesis, we generated …
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Jagged1 regulates adult neural stem cell maintenance and multipotency through activation of Notch1
… dass Jagged1 mittels seiner Wirkung durch Notch1 in der Aufrechterhaltung und in der Differenzierung der adulten neuralen Stammzellen ein zentrales Element ist. Als Folge der Inaktivierung <br>von Jagged1 können multipotente neurale Stammzellen ihr Stammzell-ähnliches <br>Potential nicht …
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Probing the druggability of the Notch1 ankyrin domain using a fragment-based approach
… small molecules binding to the ankyrin domain of Notch1 receptor.
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Molecular And Therapeutic Implications Of Notch1 Signaling In Pediatric T-Cell Acute Lymphoblastic Leukemia
… of unique features on which to base therapy. NOTCH1 mutations are of particular interest since these were reported in 37-71% of T-ALLs. The prognostic value of NOTCH1 mutations remains controversial as both favorable and unfavorable associations were reported, whereas in other studies, there …
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Investigating the Post-Translational Modification of Notch1 Intracellular Domain: From Proteolytic Cleavage to Mass Spectrometric Profiling
… the post-translational regulation of the Notch1 intracellular domain (N1ICD), focusing on its potential proteolytic processing, post-translational modification (PTM) landscape, and associated protein interactors. In the first part of the study, the role of NRDc, a zinc-dependent …
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Characterization of Notch1 and Pi3K-Pten-Akt/Mtor Pathway Interaction In Head and Neck Squamous Cell Carcinoma
… demonstrated that HNSCC cell lines bearing <em>NOTCH1</em> inactivating mutations are sensitive to PI3K and dual PI3K/mTOR inhibitors, leading us to investigate the interaction of these pathways in HNSCC. The NOTCH pathway plays key roles in cell proliferation, differentiation, and apoptosis. …
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The Tumor Suppressor Notch Inhibits Head and Neck Squamous Cell Carcinoma (Hnscc) Tumor Growth and Progression By Modulating Proto-Oncogenes Axl and Ctnnal1 (Α-Catulin)
… We were among the first to discover that NOTCH1<em> </em>is one of the most frequently mutated genes in this cancer type. The spectrum of inactivating NOTCH1 mutations in HNSCC suggested a tumor suppressive role for this protein; however, the mechanism of its function is currently …
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Role of Notch Signaling in T Cell Polarization
… I have shown that Notch signaling, particularly Notch1, plays a crucial role in Th17 polarization. By using pharmacological inhibitors and specific knockdown of Notch1, I have shown that Notch1 is necessary for Th17 differentiation. Furthermore, IL-17 promoter assays and chromatin …
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Investigating Notch/Dll4 signalling in retinal microvascular cells in health and disease
… aggregation as well as increased N-Cadherin and Notch1 expression, the latter of which correlated with increased availability of the Notch intracellular domain (NICD). The results from chapter1 implicate eNOS in promoting an epithelial-like phenotype with increased cell-cell adhesion which was …
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Investigating the role of Notch signalling during mesoderm development and cell proliferation
… novel insight, which revealed that human Notch1 forms nuclear biomolecular condensates, raised questions regarding the effect of physical interactions between Notch1 proteins and target gene RNA products on transcriptional regulation and dynamics. Here, we aimed to answer the two questions …
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Notch deficiency leads to arteriovenous malformations and altered pericyte function
… vascular permeability. Endothelial cells express Notch1, whereas pericytes express both Notch1 and Notch3. Here we show that Notch signaling is essential for pericyte function. Through genetic manipulation and pharmacological tools we show that Notch regulates pericyte recruitment and …
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Investigating the genome of Anaplastic Lymphoma Kinase-positive Anaplastic Large Cell Lymphoma
… in mutations. In particular, variant T349P of Notch1, which confers a growth advantage to cells in which it is expressed, was detected in 12% of ALK+ and ALK- ALCL patient samples. Furthermore, we demonstrate that the nucleophosphomin 1-Anaplastic lymphoma kinase (NPM-ALK) chimeric protein …
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Autonomous and non-autonomous regulation of chromatin structure during cellular senescence
… (SASP), we have recently identified that NOTCH1 can drive a unique form of senescence in adjacent cells via juxtacrine signalling. Here, we show that NOTCH1 signalling confers a dramatic impact on chromatin structure during senescence. RAS-induced senescent (RIS) fibroblasts often develop …
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Anti-Tumor Effects of The Notch Pathway In Gastrointestinal Stromal Tumors
… constitutively active intracellular domain of Notch1 (ICN-1) expression potently induced growth arrest and downregulated KIT expression. We have performed a retrospective analysis of 15 primary GIST patients and found that high mRNA level of <em>Hes1,</em> a major target gene of Notch pathway, …
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Transcription factor modulation in T-cells to improve cancer immunotherapy
… cellular differentiation across diverse tissues. NOTCH1 agonism restricted the differentiation of CAR-T derived from naïve CD4+ T-cells, and upregulated expression of AhR and c-MAF, driving heightened production of IL-22, IL-10 and Granzyme B upon tumor encounter. NOTCH1-agonized CD4+ CAR-T …
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