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 29 for “"genetically-engineered mouse models"”.
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Genetic analysis of Kmt2d loss in tumorigenesis using genetically engineered mouse models
… cancers. To address these questions, we utilized genetically engineered mouse models (GEMMs) to study the impact of <em>Kmt2d</em> loss during melanoma, lung, and urothelial carcinoma development.</p> <p> In a mutant <em>Braf</em>-driven melanoma, <em>Kmt2d</em> loss accelerated tumor development …
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Development and characterization of immunogenic genetically engineered mouse models of pancreatic cancer
… escape, we have characterized two preclinical models of immunogenic pancreatic ductal adenocarcinoma (PDAC). In order to dissect the endogenous antigen-specific T cell response in PDAC, lentivirus encoding the Cre recombinase and a tumor specific antigen (SIINFEKL, OVA[subscript 257-264]) was …
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Investigation of T cell-mediated immune surveillance against tumor-specific antigens in genetically engineered mouse models of cancer
… To assess the role of anti-tumor T cells in models that more accurately reflect the human disease, I developed new systems to introduce exogenous antigens, to mimic neoantigens, into genetically engineered mouse models of lung cancer and sarcomas. Utilizing the mouse model of lung cancer, I …
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Investigating functions of tumor-infiltrating natural killer cells in genetically-engineered mouse models of non-small cell lung cancer
… inducing activating NK cell ligands in tumors engineered to express T cell antigens, I demonstrated that NK cell activation in immunogenic tumors results in effective immune responses that restrain tumor growth, highlighting the potential for cooperation between innate and adaptive arms of the …
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Comparison of wild-type and hotspot mutant p53 interactomes: The hunt for mutant-specific binding partners & Investigation and characterization of natural killer cell responses in genetically-engineered mouse models of non-small cell lung cancer
… killer (NK) cell responses in autochthonous models of lung cancer, using lentiviral vectors that initiate tumors and express the NK cell ligand, m157. Using this model, we demonstrate that NK cells become rapidly dysfunctional during tumor progression, but can be stimulated to regain …
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An organoid platform to study alveolar stem cells in lung generation and cancer
… treatment strategies. A wide variety of models have been developed to study LADC. Cell line- and transplant-based models offer rapid and flexible platforms for discovering and testing novel therapeutics using patient-derived specimens. On the other hand, genetically engineered mouse …
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Insights into determinants of cancer susceptibility, initiation, and progression:studies on medulloblastoma and Histiocytic Sarcoma in mouse models
… of cancer development. Both projects used genetically engineered mouse models of cancer. The introductory chapter gives a brief historical introduction to cancer, background information on models of cancer, and a short description of our current understanding of cancer. Chapter two presents …
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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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LKB1, CCL2, and Macrophages: A New Axis of Endometrial Cancer Progression
… genetic, proteomic, and in vivo studies in genetically engineered mouse models show that loss of LKB1 protein is associated with high grade, high stage tumors with unfavorable clinical outcomes. However, the mechanism(s) by which LKB1 drives malignant transformation of uterine cancers …
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Fibroblast Heterogeneity In Pancreatic Cancer Immunity
… and multiplex immunohistochemistry to assess genetically engineered mouse models (GEMMs) in which we could deplete aSMA<sup>+</sup> and FAP<sup>+</sup> CAFs. We found the aSMA<sup>+</sup> and FAP<sup>+</sup> CAFs were distinct subsets with tumor restraining and tumor supporting roles, …
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Validation of AXL as a Therapeutic Target in Pancreatic Cancer
… gemcitabine. Single cell RNA sequencing of PDA genetically engineered mouse models reveals that AXL is expressed highly in tumor cells that have a mesenchymal-like phenotype and AXL expression correlates with classic markers of mesenchymal tumor cells. This AXL-positive mesenchymal PDA cell …
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Defining and Targeting Epigenetic Rewiring During Tumor Progression
… unexplored. In the current work, we utilized genetically engineered mouse models of breast cancer recurrence to evaluate the contribution of epigenetic plasticity to tumor recurrence and chemoresistance. First, we found that recurrent tumors undergo dramatic epigenetic and transcriptional …
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A Multi-Factorial Assessment of Partial Mitochondrial Complex I Impairment in Colorectal Cancer
… cell-based systems, tumor-derived organoids, and genetically engineered mouse models, this work demonstrates that partial disruption of complex I accelerates CRC tumor growth by inducing metabolic reprogramming that sustains proliferation of cancer cells despite impaired oxidative phosphorylation. …
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Functional Analysis of Daxx In Tumorigenesis of Pancreatic Neuroendocrine Tumors and Embryonic Development
… The loss of Daxx leads to early lethality in mouse embryos around E6.5. Moreover, sequencing studies have revealed the importance of DAXX in human tumors. Mutually exclusive mutations in DAXX and ATRX occur in about 30% of pancreatic neuroendocrine tumors (PanNETs). Although lots of progress …
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Elucidating the Role of BMI1 in Lung and Colon Tumor Maintenance and Progression
… types in which BMI1 is overexpressed. Using genetically engineered mouse models, we determine that in oncogenic KRAS-driven lung adenocarcinomas, with or without Trp53 deletion, genetic ablation of Bmi1 at tumor initiation induces a pronounced proliferation defect and consequently significant …
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Constructing and deconstructing cancer using CRISPR-Cas9
… particularly in the context of in vivo models of the disease. Although existing genetically engineered mouse models (GEMMs) have led to critical insights into the initiation and progression of human cancer, their use for rapid functional characterization of new cancer genes has been …
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Cd47+ Exosomes Facilitate Effective Targeting of Oncogenic Kras In Pancreatic Cancer
… normal fibroblast-like mesenchymal cells were engineered to carry RNA interference molecules to specifically target oncogenic KRAS<sup>G12D</sup>, a mutation identified in about 50% of patients with pancreatic cancer. Compared to liposomes, exosomes containing siRNA or shRNA specific to …
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A Study of The Snd1/Prmt5 Axis In Liver Cancer By Genetic Mouse Models
… SND1 has been confirmed as a driver of HCC using genetically engineered mouse models (GEMMs), though, it remains unknown if loss of SND1 or its methyl reading ability can protect against HCC formation. PRMT5 has been reported as upregulated in many cancers and may predispose hepatocytes to develop …
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Identifying Epigenetic Regulators Of Tumor Dormancy And Recurrence
… are poorly understood. Using a HER2 inducible mouse model of breast cancer, we performed a CRISPR screen to identify novel epigenetic regulators of tumor dormancy and recurrence. We identified HDAC10 and KMT2E as recurrencepromoting genes; tumor cells with Hdac10 or Kmt2e loss were depleted …
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CRISPR-mediated interrogation of small cell lung cancer
… of which remain to be functionally validated. Genetically engineered mouse models (GEMMs) of SCLC have been developed that recapitulate many key features of human SCLC. These models have been used extensively to investigate various aspects of SCLC biology, including tumor initiation, …
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