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 “"Genetic Events"”.
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The role of PAX3/PAX7-FKHR in mesenchymal stem cell myogenic differentiation and rhabdomyosarcomagenesis
… and PAX7-FKHR fusion genes respectively. These genetic events result in a molecular gain of function of the fusion protein, which is proposed to perturb the differentiation of muscle progenitor cells. Since PAX3/7-FKHR fusions result in rearrangements of PAX3/7 and FKHR genes, such that the PAX …
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The human myeloproliferative disorders: molecular pathogenesis and clonal heterogeneity
… presence of clonal diversity in the MPD and the genetic events associated with progressive disease. Mutations in MPL were identified in 4% of ET and 7% of IMF but not in PV. Three different acquired MPL mutations were identified, one of which had been reported as an inherited allele. Although MPL …
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Comparative and Functional Genomic Analysis of <i>Streptococcus Equi</i> and <i>Streptococcus Zooepidemicus</i> : Identifying Novel Vaccine Targets
… <i>S. zooepidemicus</i> strains uncovered the genetic events that have shaped the evolution of <i>S. equi</i>, and led to its emergence as a niche-adapted pathogen. This analysis provides evidence of functional loss, changes in the organisation and sequence of genes, and pathogenic …
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THE ROLE OF THE TRANSCRIPTION FACTOR DEAF-1 IN PROSTATE FUNCTION
… suggesting DEAF-1 haploinsuffciency produces a genetic defect in prostate function. The Deaf-1 knockout mice also develop lung and liver tumors and these data show a potential role of Deaf-1 in the molecular basis of tumor formation. To facilitate the elucidation of the genetic events that may …
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Studies of a restricted signature of circulating miRNAs as non-invasive biomarker in glioma: from the molecular function to the clinical application
… diagnosis and treatment. The identification of genetic and epigenetic markers has led to an integrated diagnosis, composed of a histological diagnosis, and a molecular profile of the tumour. Among the key genetic events, mutations of the isocitrate dehydrogenase (IDH) genes are noteworthy. …
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Applications of genome editing for disease modeling in mice
… about (ie noncoding DNA). Forward and reverse genetics in cells and animal models is key to discovering causal mechanisms relating molecular and genetic events to phenotypes. Therefore, the ability to sequence and edit DNA is fundamental to understanding of the role of genetic elements in …
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Role of PRAS40 in mammalian target of rapamycin (mTOR) modulation in cancer and insulin resistance
… To directly test the importance of these genetic events in mammary tumorigenesis, we assessed whether disruption of PRAS40 could alter mammary tumor occurrence in HER2 overexpressing mice. HER2 overexpressing mice expressing the activated rat Erbb2 (c-neu) oncogene under the direction of …
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Exocytosis in Type 2 Diabetes- Functional and genetic studies of hormone secretion
… thesis has been to investigate functional and genetic events that participate in the exocytotic process. First we show that SNAP25 is essential for cAMP-dependent rapid exocytosis in insulin-secreting cells, and that the effect may be mediated by binding to cAMP-GEFII (paper I). In mouse …
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Elucidating oncogenic mechanisms in human B cell malignancies
… sequencing studies have identified hundreds of genetic alterations but, for most, their contribution to disease, or their importance as therapeutic targets, remains uncertain. I optimised a novel approach to screen the functional importance of these mutations. This was achieved by reconstituting …
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Towards a B-Lymphoid Model of E2A-PBX1-Mediated Leukemogenesis: Evaluating the Impact of Hematopoietic Cell of Origin on the Transformation Properties of a Leukemogenic Transcription Factor
… Since pre-B ALL induction requires secondary genetic events, we attempted to abrogate these E2A-PBX1-mediated effects by modulating expression of the Cdkn2a locus. Loss of Cdkn2a through deletion or Bmi1 overexpression failed to ameliorate the apoptotic response, suggesting that E2A-PBX1 …
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Merlin Regulation of Mouse Spinal Cord Neural Precursor Cell Function
… In this dissertation, we use NF2 as a tractable genetic model system to define the key intracellular signaling pathways that control SC NPC function relevant to SC ependymoma formation.</p><p>In support of an essential role for the Nf2 protein (merlin/schwannomin) in SC tumorigenesis, we …
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Modeling and Characterization of Dynamic Changes in Biological Systems from Multi-platform Genomic Data
… DNA copy number alterations (CNAs) are key genetic events in the development and progression of human cancers, and frequently contribute to tumorigenesis. We propose a statistically-principled in silico approach, Bayesian Analysis of COpy number Mixtures (BACOM), to accurately detect genomic …
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An Examination of the Broader Autism Phenotype in Simplex and Multiplex Families
Non-inherited genetic mutations are more prevalent in families with only one individual diagnosed with autism spectrum disorder (ASD; simplex) whereas inherited genetic risk factors may play a greater role in families with more than one affected individual (multiplex). Behavioral genetic studies …
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Early Blood Cell Formation "in sickness and health, ´till death do us part"
… it can also provide with clues on possible pathogenetic events in cases of altered hematopoiesis like leukemia or in the aging individual. In Article I, we have investigated the role of tumor necrosis factor (TNF) in the regulation of HSC homeostasis. We found TNF to negatively regulate HSC …
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The role of the Dnmt3aR882H mutation in the evolution of clonal haematopoiesis.
DNMT3A mutations are very frequent events in clonal haematopoiesis of indeter- minate potential (CHIP), and considered one of the earliest genetic events during the development of haematopoietic malignancies. Individuals with CHIP, in spite of having a normal full blood count are at increased risk …
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Molecular Genetic Characterization of Acute Lymphoblastic Leukemia with a Poor Prognosis
… higher age. The presence of specific acquired genetic abnormalities is important for diagnosis, prognostication, and treatment stratification. ALL can be further categorized into subgroups defined by structural or ploidy abnormalities. One such subgroup, hypodiploid ALL (<46 chromosomes) is …
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Stress response genes in the human proximal tubules
… their elevated basal levels, indicating that the genetic events that resulted in the immortalization of the HK-2 cells also elicited a stress response for hsp 27 and hsp 60, but not for hsp 70. Thus, there are differences in the regulation of the stress response between the immortal HK-2 and …
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A Compendium of Genetic Drivers for Oesophageal Adenocarcinoma defines Prognostic and Therapeutic Biomarkers for use in the Clinic
… rapidly rising incidence. Understanding of the genetic events driving OAC development is limited, and there are few molecular biomarkers for prognostication or therapeutics. This study aimed to use a large cohort of genomically characterised OACs to determine the landscape of genetic driver …
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Basal-like breast cancer: modeling its initiation and characterizing novel EGFR variants
… mostly due to our poor understanding of the key genetic events that lead to the onset and/or maintain this subtype of BC. As a result, we currently lack targeted therapies that are otherwise very effective in some of the better understood subtypes of BC. Therefore we set to work on deciphering …
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Oncogenic Kras and Telomere Biology In Crc Progression
… to metastatic disease, it is clear that genetic events beyond <em>KRAS </em>activation play a pivotal role in driving metastases. Notably, patients, irrespective of <em>KRAS</em> mutations, exhibit a nearly identical lymph node metastatic rate of approximately 40%. In order to explore …
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