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 40 for “"Phosphoproteomics"”.
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Phosphoproteomics analysis of Alzheimer's disease
Alzheimer's disease (AD) is a form of dementia characterized by the appearance of amyloid-[beta] plaques, neurofibrillary tangles, and inflammation in brain regions involved in memory. Despite numerous clinical trials, a limited understanding of disease pathogenesis has prevented the development of …
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Development Of Kinase Catalyzed Biotinylation To Study Phosphoproteomics
… occurs with catalytic efficiency appropriate for phosphoproteomics application. Next, the susceptibility of the biotin tag to phosphatases was characterized and found that the phosphorylbiotin group was relatively insensitive to protein phosphatases. Importantly, robust kinase-catalyzed …
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Translational phosphoproteomics methods to identify biomarkers and novel therapeutic targets
… platform using mass spectrometry imaging, phosphoproteomics and multiplexed tissue imaging for mapping drug distribution, target engagement, and adaptive response to gain insights into heterogeneous response to therapy. In the last part of thesis, we demonstrate the application of …
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Development of Dendrimer-based Technologies for Phosphoproteomics and Glycoproteomics in Biomarker Discovery
The dynamics of post-translational modifications (PTMs) of proteins keeps cells adapting to the ever-changing microenvironment by regulating protein structure and function in the real-time mode. Of all PTMs, protein phosphorylation and glycosylation are undoubtedly two of the most common and …
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Development of mass spectrometry based technologies for quantitative cell signaling phosphoproteomics : the epidermal growth factor receptor family as a model system
Ligand binding to cell surface receptors initiates a cascade of signaling events regulated by dynamic phosphorylation on a multitude of pathway proteins. Quantitative features, including intensity, timing, and duration of phosphorylation of particular residues play a role in determining cellular …
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Regulation of tumor necrosis factor-alpha induced apoptosis via posttranslational modifications in a human colon adenocarcinoma cell line
(cont.) phosphoproteomics technology, IMAC/LC/MS/MS, [approximately] 200 phosphosites were identified from HT-29 cells, some of which were detected only from insulin-treated cells. Our phosphoproteomics approach also enabled us to detect alteration of both known and unknown phosphorylation states …
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Mechanistic Characterization of RTK Signaling Networks Using Phosphoproteomic Approaches
… need to be deeply understood. The field of phosphoproteomics has advanced over the past few decades to allow analysis of phosphorylated proteins with increased sensitivity and accuracy. Using these methods in combination with a systematic mutational strategy that evaluates the network …
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Statistical methods to infer kinase activities and kinase-substrate interactions using phosphoproteomic data
… (MS) based phosphorylation studies (i.e. phosphoproteomics) has revolutionized the study of kinase signalling, allowing for the quantification of thousands of phosphorylated protein sites.However only a small fraction of these events are associated with a regulatory kinase. In this work, …
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Analysis of the understudied parts of the phospho-signalome using machine learning methods
… on kinase specificities and high throughput phosphoproteomics and transcriptomic data. The network was validated using independent high throughput data and used to identify novel kinase-kinase regulatory interactions. This project was done in collaboration with Brandon Invergo, a postdoc in …
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Elucidating the Role of the Essential Kinase TgGSK in the Human Parasite Toxoplasma Gondii
… cycle. We determined through microscopy and phosphoproteomics that TgGSK may play its role in parasite division through an interaction with the centrosome, an organelle which is a main feature of cell division in many organisms. Our findings suggest that TgGSK also regulates messenger RNA …
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Analysis of CDPK1 targets identifies a trafficking adaptor complex that regulates microneme exocytosis in Toxoplasma
… I discuss combining sub-minute resolution phosphoproteomics and bio-orthogonal labeling of kinase substrates in T. gondii to identify 163 proteins phosphorylated in a CDPK1-dependent manner. In addition to known regulators of secretion, I identify uncharacterized targets with predicted …
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Oncogene-driven post-transcriptional regulation in lung cancer
… may be tumorigenic. Then, with quantitative phosphoproteomics, I found that KRAS variant cells differentially phosphorylated SR protein phosphosites. To determine how KRAS may regulate alternative splicing, I analyzed unique RNA sequencing profiles of lung adenocarcinoma cells ectopically …
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Proteomic Analysis of WNT Signaling and Metabolism of Fibrolamellar Hepatocellular Carcinoma
… as well as transcriptomics, proteomics, and phosphoproteomics analysis to investigate some of the ways mitochondria are altered in FLC.</p>
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Identification of the ERK5 Kinase as a Key Regulator of Embryonic Stem Cell Pluripotency
… pluripotency.<br/><br/>I employ quantitative phosphoproteomics to elucidate molecular mechanisms by which ERK5 functions in mESCs. Within a cohort of high confidence ERK5responsive phosphopeptides, I identify a dual phosphosite on the core naïve pluripotency transcription factor KLF2. ERK5 …
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Identification of the molecular pathways that mediate cytokine induced immunopathology of the gut epithelium
… different cell death pathways (Chapter-III). Phosphoproteomics identified potential target substrates for sustained JAK1 and JAK2 kinase activity. These JAK1/2 substrate proteins are associated with epithelial junctions, cell adhesion and cell-cell interactions, highlighting the importance of …
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Daily organisation of cellular physiology by mTOR kinase
… characterise them by quantitative proteomics and phosphoproteomics. I find that, in both cultured cells and in mouse liver, soluble protein rhythms are modulated by mTORC activity. Through pharmacological inhibition of mTORC1 and 2 I explore how circadian regulation of physiological outputs, such …
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The Mycobacterium tuberculosis protein O-phosphorylation landscape
… (GoF) mutants with mass spectrometry (MS)-based phosphoproteomics. We found that the Mtb phosphoproteome is 5x larger than was previously reported. By identifying hypo-phosphorylated proteins in the LoF mutants and hyper-phosphorylated protein in the GoF mutants, we comprehensively identified …
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With No Gly-Loop Family of Kinases
… understanding of the network's functions. Phosphoproteomics data indicated that many PV resident proteins are phosphorylated, including ones that have roles is the biogenesis and maintenance of these tubular networks. Since phosphorylation is a common method to regulate protein functions we …
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Elucidating the role of the EGFR-family members in cell motility through the use of novel engineered bivalent ligands
… on these results, a mass spectrometry (MS)-based phosphoproteomics approach to quantitatively map cellular signaling events mediated by Her-3 downstream of Met proceeded. The thesis concludes by quantitatively exploring the relationship between the measured signals of phosphorylated proteins and …
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