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 22 for “"shRNA knockdown"”.
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Prkca: Identification of A Novel Downstream Target of Wt1
… cells of the developing kidney. siRNA knockdown, in-vivo ablation, and tet-inducible expression of <em>Wt1</em> each independently confirm regulation of <em>Prkcα</em> expression by Wt1 at both RNA and protein levels, and investigation into possible WT1 binding sites in <em>PRKCα</em> …
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Model studies aimed toward constructing PI3K pathways in leukemia T-cells from shRNA knockdowns
… capture networks is unexplored. Motivated by a shRNA knockdown experiment on leukemia cell lines treated with a PI3K inhibitor, we sought to devise and test a method to reconstruct the relevant network, which could be used to gain a deeper understanding of the networks involved in PI3K signaling …
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Inhibition of Mitochondrial Translation as a Therapeutic Strategy for Acute Myeloid Leukemia
… in AML cells over normal hematopoietic cells. ShRNA knockdown of TuFM mitochondrial translation factor in leukemia cells reproduced TIG anti-leukemia target effects previously described. We discovered that primary AML CD34+/CD38- stem cells have greater mitochondrial mass (3-fold, n=5) than …
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Suppression of telomerase component dyskerin in human haematopoietic progenitor cells
… dependent and independent effects. Inducible shRNA knockdown lentiviral vectors targeting either DKC1 or TERC were constructed for transduction into human HPCs. Using this model, it was confirmed that depletion of either dyskerin or TERC effectively suppressed telomerase activity and reduced …
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Targeting Aldehyde Dehydrogenases in NF2-null Meningioma and Schwannoma
… in meningioma cells and tissue. ALDH1A3-targeted shRNA knockdown deplete colony formation, proliferation, and ALDH activity in these cells.<br/><br/>The ALDH inhibitors nifuroxazide, DIMATE, and ABD 0171 reduce the proliferation and/or survival of meningioma cells. ABD 0171 also reduces tumour …
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The Diversity of FHF-mediated Ion Channel Regulation
… FGF13 is observed within the soma and dendrites. shRNA knockdown and rescue strategies showed that FGF14 regulates axonal VGSCs, while FGF13 only affects VGSCs in the somatodendritic compartment. Thus, FGF13 and FGF14 have nonredundant roles in hippocampal neurons, with FGF14 acting as an …
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DELINEATING REGULATORY PATHWAYS OF NOVEL CANCER STEM CELL MARKER, DCLK1-S, FOR TARGETING COLON CANCER STEM CELLS
… of DCLK1, therefore my second goal was to use shRNA knockdown methods to specifically target DCLK1-S isoform, in order to delineate the biological role of cancer specific DCLK1-S isoform. The results of our studies suggest that DCLK1-S mediates the activity of transcription factor, NFATC2 (via …
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The role of the tumor suppressor gene, NF2, in the development of malignant mesothelioma
… was reduced in "normal" mesothelial cells by shRNA knockdown. In both in vitro models, alterations in NF2 expression resulted in significant changes in cell cycle mechanisms, including proliferative, apoptotic, and cell cycle arrest. These events were linked to aberrant p53 function. Finally, …
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The role of the tumor suppressor gene, NF2, in the development of malignant mesothelioma
… was reduced in "normal" mesothelial cells by shRNA knockdown. In both in vitro models, alterations in NF2 expression resulted in significant changes in cell cycle mechanisms, including proliferative, apoptotic, and cell cycle arrest. These events were linked to aberrant p53 function. Finally, …
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Modulation of Clr-b Ligand for the Inhibitory NKR-P1B NK Cell Receptor in Response to Transformation and Genotoxic Stress
… through pharmacological inhibition of MEK1/2 or shRNA knockdown of Erk2. However, Erk2 alone is not sufficient to induce Clr-b downregulation and requires activation from upstream signals. All together, our results explore the role of genotoxic stress and transformation on the modulation of …
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Lgr5 Regulation of Stat3 Signaling and Drug Resistance In Colorectal Cancer
… reported that loss of LGR5 expression, through shRNA knockdown (KD) or CRISPR knockout (KO) in multiple CRC cell lines, increased both chemotherapy resistance and proliferation, however the complete mechanisms by which this occurs is unknown. Through comprehensive western analysis, we discovered …
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The Role of FBXO7 in Mitochondrial Biology and Parkinson's Disease
… PD models. The models examined included FBXO7 shRNA knockdown SH-SY5Y cell lines, FBXO7 CRISPR knockout SH-SY5Y cell lines, primary patient fibroblasts with a FBXO7 mutation, and MEFs and tissues from a Fbxo7 KO mouse. My analysis of fibroblasts from a patient without FBXO7 expression revealed …
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Understanding collagen-l folding and misfolding
… of these proteins in collagen-I processing using shRNA knockdown of proteins of interest. Chapter Four: Creation and Validation of Constructs for the Independent Expression of the Collagen-I C-Propeptide Domains The collagen-I C-propeptide domains are responsible for collagen-I chain selectivity …
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The Role of Viral Protein pUL21a in Human Cytomegalovirus Infection
… of the APC during HCMV infection. Finally, shRNA knockdown of the APC activator Cdh1 and to a lesser degree APC8, significantly restored late gene expression of the UL21a mutant virus, suggesting the APC has antiviral activity for HCMV. Thus, we propose that one mechanism for pUL21a to …
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The chemokine CCL2/CCR2 signaling mediates cancer associated fibroblasts-cancer cells interaction and promotes basal-like breast cancer progression
… of CCL2 expression by CRISPR mutation or shRNA knockdown in human or mouse CAFs significantly reduced tumor growth in the co-graft model. Fibroblasts condition medium or recombinant CCL2 directly promoted CA1D cancer cell growth in vitro. Mutation of the CCL2 receptor CCR2 receptor in CA1D …
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A role for the SHANK1 scaffold protein in experience-induced synaptic plasticity and memory consolidation
The processes by which the brain acquires, stores, and retrieves external information has been an extensively researched field in psychology. Findings from these studies have overwhelmingly suggested that plasticity of neuroanatomical networks across development and during various experiences …
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Investigating mechanisms and biological functions of the bHLH/PAS transcription factors SIM1 and ARNT2
… a doxycycline (Dox) inducible short hairpin RNA (shRNA) system is an attractive approach to deplete gene expression without irreversibly damaging a gene and can allow normal embryonic development to occur prior to studying effects of reduced protein levels in adult tissues. In this study, we …
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Validating the WD Repeat Protein CDC40 as a Potential Therapeutic Target for Lung Cancer
… this study, I characterized the effects of CDC40 knockdown in a panel of lung cancer cells. I show that CDC40 knockdown induced cell cycle defects resulting in strong growth inhibition and activation of late-stage apoptotic markers in all lung cancer cells tested. To further understand the …
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Investigating Notch/Dll4 signalling in retinal microvascular cells in health and disease
… We demonstrated using lentiviral-mediated shRNA knockdown that Dll4 has important roles in mediating cell-cell junction and that removal of Dll4 induces an enlarged senescent-like phenotype. These findings were linked to decreased Notch1 activation evidenced by reduced NICD levels …
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Identification of ITGBL1: A Novel Regulator of Adipogenesis
… differentiation in vitro. Here, we show that shRNA or CRISPR-mediated inactivation of ITGBL1 expression increases the propensity of mesenchymal stem cells to undergo adipocyte differentiation. RESULTS: In order to properly assess the potential adipogenic role of the top regulated genes from …
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