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Theses/Dissertations

2022

Biomedical Sciences

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Full-Text Articles in Engineering

Erk3 And Dgkζ Interact To Modulate Cell Motility In Lung Cancer Cells, Amanda Myers Jan 2022

Erk3 And Dgkζ Interact To Modulate Cell Motility In Lung Cancer Cells, Amanda Myers

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Extracellular-regulated kinase 3 (ERK3) is overexpressed in a variety of cancers, including lung cancer. This atypical mitogen-activated protein kinase (MAPK) has a unique structure which includes a C34 domain and C-terminus and about which relatively little is known. ERK3 has been demonstrated to promote cell migration and metastasis in multiple cancer types. A yeast two-hybrid assay using ERK3 as bait indicated Diacylglycerol kinase ζ (DGKζ) is a binding partner. DGKζ is an isoform in the DGK family, all the members of which phosphorylate the lipid diacylglycerol (DAG) to generate phosphatidic acid (PA). DGKζ was shown to promote migration in mouse …


Fbxl16 Promotes Breast Cancer Cell Growth And Diminishes Fulvestrant Responsiveness By Stabilizing Erα Protein, Krushangi Nirav Shah Jan 2022

Fbxl16 Promotes Breast Cancer Cell Growth And Diminishes Fulvestrant Responsiveness By Stabilizing Erα Protein, Krushangi Nirav Shah

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Breast cancer is the most prevalent cancer in women. Approximately 75% of breast cancers are estrogen receptor alpha positive (ER+) and are treatable with endocrine therapies and/or CDK inhibitors. However, endocrine therapy (ET) resistance and metastasis are major obstacles in advanced ERα+ breast cancer (ER+ BCa) therapeutics. Upregulated oncogenic ERα activity plays critical role in progression of ER+ BCa. One essential mechanism of regulating ERα signaling is the ubiquitination-dependent proteasomal degradation of ERα. Owing to its direct effect on ERα degradation, fulvestrant is a first-line FDA-approved ET for metastatic and locally advanced breast cancer and a second-line drug for treatment …


The Role Of Son In Chromatin-Mediated Gene Expression, Melissa Jordan Ward Jan 2022

The Role Of Son In Chromatin-Mediated Gene Expression, Melissa Jordan Ward

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Gene expression in mammalian cells requires complex nuclear choreography, and there is increasing evidence that spatiotemporal organization of chromatin and nuclear compartments plays an important role in gene expression. In this dissertation, I examined the function of SON, a splicing factor with a known role in nuclear organization, in chromatin-mediated gene expression. SON association with a transcriptionally inactive U2OS 2-6-3 reporter gene array provided a useful model to study SON’s chromatin dynamics. I demonstrated that SON associates with the inactive but not the activated array, and that SON’s RNA binding domains are not necessary for that association. Second, I discovered …


Reciprocal Regulation Of Transketolase-Like 1 And Hypoxia-Inducible Factor 1 Alpha In Metabolic Reprogramming And Growth Of Diffuse Midline Glioma, H3 K27m-Mutant, Christopher Andrew Waker Jan 2022

Reciprocal Regulation Of Transketolase-Like 1 And Hypoxia-Inducible Factor 1 Alpha In Metabolic Reprogramming And Growth Of Diffuse Midline Glioma, H3 K27m-Mutant, Christopher Andrew Waker

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Diffuse midline glioma, K27M-mutant (DMG) are intractable brain tumors, primarily occurring in the pediatric and adolescent population. Patients have a median survival of less than one year after diagnosis. A lack of therapeutic targets has been a barrier to improvement in patient survival. Irradiation therapy improves symptoms while chemotherapy and surgical intervention, for the most part, have not yet demonstrated utility for treatment. DMG are characterized by a histone H3 mutation that results in the genome-wide loss of epigenetic-repressive marks on K27 and is associated with the misexpression of genes, like Cancer/Testis antigens. A member of this group, transketolase-like 1 …