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 11 of 11 for “"chemical screen"”.
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Targeting tGLI1-positive Breast Cancer with Ketoconazole
… therapeutic target. Using a synthetic lethality chemical screen approach, we found that ketoconazole, an FDA-approved azole antifungal, was able to kill tGLI1-expressing cancer cells with increased efficacy against the CSC subpopulation. Additionally, ketoconazole selectively inhibited the …
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Cellulose biosynthesis inhibitors modulate defense transcripts and regulate genes that are implicated in cell wall re-structuring in arabidopsis
… Biosynthesis Inhibitors (CBIs). In this case, chemical screen for swollen organ phenotype has proved to be an important technique to identify the genes that are directly or indirectly involved in cellulose biosynthesis. In the present research, a number of synthetic CBIs were obtained through a …
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Identification of a first in-class integrin enhancing small molecule for the treatment of Duchenne Muscular Dystrophy
… DMD. Utilizing a high-throughput drug discovery chemical screen, we identified SU9516, an adenosine mimetic, as an enhancer of ITGA7 expression, the gene encoding integrin α7. We found SU9516 increased α7B integrin protein levels in C2C12 and immortalized human DMD myotubes. Preclinical studies …
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The Integration of Metabolite and Hormone Signalling Drives Seedling Development
… with sugars during seedling development, a chemical screen was performed in search of compounds that modify responses to sucrose. This screen identified an interaction between the folate inhibitor sulfamethoxazole (SMX) and sucrose that resulted in changes to auxin signalling and …
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Structure, Mechanism and Chemical Modulation of the Protein Kinase-nuclease Dual-enzyme IRE1
… the manipulation of IRE1 signaling output using chemical tools. To better understand IRE1 mechanism, I determined the crystal structure of IRE1cyto bound to ADP. Structural and mutational analyses uncovered a probable novel IRE1 nuclease active site, allowing a catalytic mechanism of RNA cleavage …
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Characterization of Host Factors and Anti-viral Compounds for Diverse Mosquito-borne Flaviviruses
… pipeline. We used a genome-scale RNAi-based screen followed by a chemical screen of FDA-approved therapeutics to identify scores of novel dengue virus (DENV) human host dependency factors (HDF) and identified more than 20 potential anti-Zika virus (ZIKV) therapeutics. </p><p>Two genes in …
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Investigating the role of the Hippo pathway in epithelial-mesenchymal transition and drug resistance
… results from a quantitative, high-throughput chemical screen in Panc02.13 cells, a pancreatic ductal adenocarcinoma (PDAC) cell line. I confirmed previously annotated resistances and sensitivities conferred by YAP-activity and identified a significant resistance to MEK inhibition (MEKi) in …
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Use of Genetically Encoded Tools to Interrogate Mechanisms of Glutathione Homeostasis from Mitochondria to Mice
… transporter by performing CRISPR-Cas9 screens that relied upon the assumption that the mitochondrial glutathione transporter(s) is/are essential for cell proliferation, and that enabling mitochondrial glutathione synthesis would enable identification of these no-longer essential genes. …
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Leveraging cell micropatterning technology for rapid cell-based assessment of chemical toxicity and population variation in toxicity susceptibility
… chemistry, the number of novel synthetic chemicals has skyrocketed over the past three decades, bringing about tremendous advances in medicine and material science. At the same time, the massive libraries of existing chemicals coupled with the unprecedented rate of new chemical generation …
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High-throughput approaches to sourcing of human hepatocytes for cell-based therapies
… the failure of organs serving a multitude of biochemical functions, such as the liver, requires cell-based therapies. Such therapies should ideally employ human cells due to immunological concerns and the substantial differences between animal and human hepatocellular functions. Human cell lines, …
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Genetic and Chemical Dissection of BloodBrain Barrier Development in Zebrafish
… model for unbiased genetic and small molecule screens. To fulfill these goals, we produced a BBB reporter line, Tg(glut1b:mCherry)sj1, to characterize the in vivo development of the BBB. We were able to show through live imaging and proof-of-principle experiments, that the processes of CNS …