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 “"genetically engineered mouse model"”.
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Interrogation of Changes in Cell State during Tumor Evolution of a Genetically Engineered Mouse Model of Lung Adenocarcinoma
In genetically engineered mouse models of lung adenocarcinoma (LUAD), tumors become more heterogeneous and dysregulate cell identities as they progress and evolve. In this thesis, single-cell RNA-sequencing technology was utilized to understand dynamic changes that occur during tumor evolution both …
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Integrated multiparametric deep spatial phenotyping of mouse models of lung adenocarcinoma
… predict features of tumor tissues taken from a genetically engineered mouse model (GEMM) of lung adenocarcinoma. I extracted biomarker expression levels and morphological, textural, and spatial motifs of single cells from the imaging data and used these features to train algorithms to predict …
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HISTONE LYSINE METHYLTRANSFERASE NSD3 GOVERNS TRANSCRIPTIONAL PROGRAMS THAT DRIVE PANCREATIC NEUROENDOCRINE TUMORS (PANNETS)
… for PanNET patients. Additionally, pre-clinical models that more accurately represent disease are an urgent necessity for translational studies.</p> <p>This dissertation directly addresses these challenges by identifying histone lysine methyltransferase (KMT) NSD3 as a critical oncogenic driver …
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Novel Small Molecule Induces Apoptosis in Malignant Peripheral Nerve Sheath Tumors of Neurofibromatosis Type I
… efficacy. In this study, we exploited a robust genetically-engineered mouse model of MPNST that recapitulates human NF1 associated MPNST to identify a novel small chemical compound that inhibits tumor cell growth. Compound 21 (Cpd21) inhibits growth of all available in vitro models of MPNST and …
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PRUNE_1 INVOLMENT IN TNBC ENHANCING CANCER METABOLISM
… with cytoskeleton proteins and kinases. Using a genetically engineered mouse model (GEMM) of metastatic TNBC (MMTV-Prune1/Wnt1), Prune1 was found to enhance glycolysis and OXPHOS, promoting lung metastases by inhibiting GSK-3 activity. Prune1's mitochondrial localization and interaction with …
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Functional Characterization of the C-terminal Cholinesterase-Like (ChEL) Domain of the Thyroid Hormone Precursor Protein
… the thyroid histological characteristics of a genetically engineered mouse model built for selective expression of the Tg-ChEL domain. Objective 2 establishes an <em>in vitro</em> system using recombinant AChE as a reporter to enable future functional testing of ChEL domain mutations linked to …
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Assessing the temporal role of miR-200 loss in murine models of NSCLC
… In this study we have developed a novel genetically engineered mouse model (GEMM) and derived primary cell lines from them to explore the role of microRNA-200 in early EMT and immune changes. Our model combines conditional activation of Kras<sup>G12D</sup>, Trp53<sup>R172H</sup>, and …
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Modulation of the tumor microenvironment by the CXCR4 antagonist AMD3100 in pancreatic and colorectal adenocarcinoma
… PDAC. In the KRasG12D; p53R172H; Pdx1-Cre (KPC) genetically engineered mouse model of PDAC, T cells are excluded from tumour nests and this effect is related to the chemokine CXCL12 produced by FAP+ stromal cells. Targeting the CXCL12/CXCR4 pathway with AMD3100, a CXCR4 antagonist, resulted T …
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A Gain-of-Function Role of Apolipoprotein E2 in Melanoma Progression
… the generation and characterization of a genetically engineered mouse model for melanoma that expresses each of the human APOE alleles. I show that this autochthonous model closely recapitulates the APOE2>APOE3>APOE4 order of melanoma progression observed in human patients. Transcriptomic …
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Finding Common Ground to Treat Primary and Metastatic Cancer: The Potential of Targeting Tumor Stroma
… via immune suppression and immune-independent remodeling of the stromal microenvironment. Additionally, using FAP-deficient mice, I found that FAP protease promotes early malignant cell seeding and pulmonary metastatic outgrowth, possibly through regulating coagulation pathways and the …
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The pathological and genomic impact of CTCF depletion in mammalian model systems
… and its implications for carcinogenesis. In a genetically engineered mouse model, Ctcf hemizygous cells showed modest but robust changes in almost a thousand sites of genomic CTCF occupancy; these were enriched for lower affinity binding events with weaker evolutionary conservation across the …
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A three-dimensional agent-based model of glioblastoma with applications towards in vitro and in vivo therapy simulation
… we developed a three-dimensional agent-based model of glioblastoma. The model incorporates rules governing cell proliferation, migration, and intercellular interactions between cancer cells and cytotoxic T cells. The model was parameterized using data from a genetically engineered mouse model …
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Identifying genes that are required for the maintenance of pancreatic ductal adenocarcinoma
… Ral. These genes were tested in the context of mouse cell lines derived from a genetically engineered mouse model of PDAC with conditional mutations in Kras G12D and p53. An individual gene-by-gene approach and a pooled high-throughput screening strategy were taken to identify important genes. …
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A broadened HLA ligandome uncovers new immunotherapy targets for pancreatic cancer + A prime editor mouse to model a broad spectrum of somatic mutations
… In Chapter 3, I report the development of a genetically engineered mouse model (GEMM) for performing prime editing in vivo. This system represents a rapid alternative to traditional cancer mouse models, which often take months or years to develop. Through a Creinducible prime editor enzyme …
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In Vivo Functional Significance of Ccat2 Long Non-Coding Rna In Myelodysplastic Syndrome
… processes that drive tumorigenesis using a genetically engineered mouse model. We generated transgenic mice for each <em>CCAT2</em> allele using random integration approach in C57Bl6/N background.</p> <p>CCAT2(G/T) mice displayed spontaneous induction of widespread pancytopenias with …
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Evaluation of Altered Kras Codon Bias and NOS Inhibition During Lung Tumorigenesis
… we created a knock-in <italic>Kras<super>ex3op mouse in which synonymous mutations in exon 3 converted codons from rare to common. These mice had reduced tumor burden and fewer oncogenic mutations in the <italic>Kras<super>ex3op allele following carcinogen exposure. The reduction in …
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Transcriptional regulation of metastatic progression in lung adenocarcinoma
… the major subtype of lung cancer. Using a genetically-engineered mouse model and derivative cell lines, we showed that metastatic lung adenocarcinoma cells are capable of forming proteolytic membrane protrusions known as invadopodia to degrade the extracellular matrix. The formation and …
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Calcium Remodeling through Different Signaling Pathways in Heart Failure: Arrhythmogenesis Studies of Pyk2, Dystrophin, and β-adrenergic Receptor Signaling
… and concomitant structural and functional remodeling, especially Ca handling. Ca is critical in both the electrical and mechanical properties of cardiac myoctyes, and much is known about ionic currents and the normal excitation-contraction coupling process. In heart failure, distinct impaired …
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Myxoid Liposarcoma: Models and Mechanisms of Sarcomagenesis and Response to Radiation Therapy
… murine sarcoma cell lines from a novel FUS-CHOP genetically engineered mouse model (GEMM). ChIP-seq/CUT&RUN mapped genome-wide binding sites of FUS-CHOP and identified DNA-binding motifs for the fusion oncoprotein. Co-IP of irradiated human MLPS cell lines were performed to evaluate …
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Leveraging copper chelators as targeted therapy for BRAFV600E mutant thyroid cancer
… PTC cells. TM was also effective in a genetically engineered mouse model of BrafV600E-mutant PTC; oral TM reduced tumor burden as well as a clinical BRAF inhibitor. This in vivo effect was attributed to a reduction of phospho-Erk1/2 signaling in the tumors. Additionally, long-term …
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