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 15 of 15 for “"TSC1"”.
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The PI3-Kinase/TSC Pathway: A Role in Neural and Renal Development and Pathology
… downstream pathways. One AKT substrate is the TSC1/2 protein complex, which controls protein synthesis and cell growth through regulating mTOR activity. AKT inhibits TSC1/2 complex by directly phosphorylating TSC2, and in turn releases the inhibition of TSC1/2 complex on mTOR. Thus, loss of …
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Molecular genetic investigation of the variability of the GTPase activating protein- (GAP-) related domain of the tuberous sclerosis-2 (TSC2) gene in TSC patients and healthy subjects
… as causing TSC when they are defective: TSC1 on chromosome 9q34.3 codes for the protein hamartin and TSC2 on chromosome 16p13.3 codes for tuberin. Tuberin shows homology to GTPase activating proteins (GAPs) and hamartin and tuberin may interact with one another to control the cell cycle, …
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Prevalence of Premature Ovarian Failure In Women With Tuberous Sclerosis
… Inactivating mutations in either the <em>TSC1</em> or the <em>TSC2</em> gene cause most cases of TSC. Recently, the use of ovarian specific conditional knock-out mouse models has demonstrated a crucial role of the TSC genes in ovarian function. Mice with complete deletion of <em>Tsc1</em> …
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Intrinsic Mechanisms that Regulate T Cell Homeostasis and Function
… models, in which the targets of gene deletion, TSC1 and DGK, are molecules that regulate signals emanating from the TCR. Additionally, we have demonstrated that both of these molecules negatively regulate the mammalian target of rapamycin (mTOR) in both naïve and activated T cells. mTOR is a …
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Automated, highly scalable RNA-seq analysis
… sclerosis with a neuron-specific knockout of Tsc1. We show that upregulation of the serotonin receptor Htr2c causes aberrant calcium spiking in the Tsc1 knockout mouse, and implicate it as a novel therapeutic target for tuberous sclerosis. The third chapter of this work investigates …
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The Potential Role of Insulin (and Stress Response) Pathway Components In Breast Cancer Development and Progression
… SNPs in insulin-signaling pathway genes, IGF1, TSC1, IGFBP2, IRS1, TCF7L2, IGF1R, and PPARA, if significantly associated with tumor receptor status, provide evidence for a connection between insulin metabolism and the determination of breast tumor subtypes. The CC genotype of the TSC1 …
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Mtorc1 Signaling In Memory Formation and Dysfunction
… regulated by the tuberous sclerosis complex (TSC1/2). When ATP and growth factors are available, TSC1/2 is inhibited and mTORC1 activity can be restored. In a complementary regulatory pathway, amino acids signal to mTORC1 through the Rag GTPases and Ragulator complex, which modulate the …
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Developing Fluorescent Tools to Dissect the Role of Tuberin at Mitotic Onset
… caused by inactivating mutations in either the TSC1 or TSC2 gene encoding for Hamartin and Tuberin, respectively. Mechanistically, Hamartin and Tuberin form a tumour suppressor complex by negatively regulating the mTORC1 pathway and inhibiting protein synthesis. Our lab has characterized how …
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Targeting Glutamine Metabolism in Kidney Development and Polycystic Kidney Disease
… studies revealed the co-ablation Lkb1 along with Tsc1, a gene known to play a role in human PKD, within the developing renal epithelia prompted a drastic acceleration in the timing, number, and size of cyst formation. We utilized in vitro cell culture coupled with ex vivo culture of embryonic …
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Characterization and Treatment of A Novel Mouse Model of Tsc-Associated Autism
… disorder caused by mutations in either <em>TSC1 </em>or <em>TSC2.</em> The proteins of these genes form a complex to inhibit the mammalian target of rapamycin complex 1 (mTORC1), which controls protein translation and cell growth. TSC causes substantial neuropathology, often leading to …
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Characterizing and Treating The Neuropathology of Tuberous Sclerosis Complex In The Mouse
… caused by inactivating mutations in either <em>TSC1</em> or <em>TSC2</em>, whose protein products are known inhibitors of mTORC1, an important kinase regulating translation and cell growth. Nonetheless, neither the pathophysiology of the neurological manifestations of TSC nor the extent of …
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Sleep Disturbances in Adults with TSC: Influences of Treatment and Clinical Features
… caused by pathogenic variants in the <em>TSC1</em> or <em>TSC2</em> genes. TSC is characterized by a multisystem, neurocutaneous phenotype including skin lesions, hamartomas, and epilepsy. Additionally, TSC can present with an array of behavioral, psychiatric, academic, psychosocial, …
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Therapeutic targeting of DGKA-mediated macropinocytosis in lymphangioleiomyomatosis
… caused by mutations in tumor suppressor genes TSC1 and TSC2. Spontaneous biallelic mutations in these genes can give rise to sporadic LAM. Mammalian target of rapamycin complex I (mTORC1), a master regulator of cellular anabolic metabolism is hyperactivated in LAM cells. Upregulation of protein …
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Identification of determinants of sensitivity to duocarmycin analogues: A class of potent anti-cancer drugs
… proteins such as tuberous sclerosis complex (TSC1 and TSC2) and STK11 were identified as potential markers to duocarmycin analogues cytotoxicity.
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Neural Mechanisms of Homeostatic Need and Reward
… mice. In contrast, a POMC-specific deletion of Tsc1, which leads to a cell specific increase of mTOR activity, resulted in leptin resistance in chow-fed animals and reduced leptin sensitivity in these and ob/ob mice. In ob/ob-POMCtsc1-/- mice, rapamycin did not reduce food intake or adiposity in …