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 28 for “"Kinome"”.
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Elucidating the Secreted Bacterial Kinome
In the post-genomic era, millions of amino acid sequences have been acquired and revealed a remarkable diversity among protein families. This is especially apparent in pathogenic species where host and pathogen participate in an intense evolutionary arms race, and horizontal gene transfer is …
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Screening for kinases regulating subcellular localization of clock proteins using human kinome library
… Plasmids and cloning 6 B. Establishment of human kinome expression library 9 C. Cell culture and transfection 9 D. Fluorescence microscopy 11 E. Quantitative real-time RT-PCR 12 F. Cell lysis 2 G. Western blotting 13 H. Immunoprecipitation (IP) and λphosphatase treatment 14 I. Fly genetics …
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In Vivo Kinome Screen Reveals Non-Canonical Cdk-Driven Metabolic Adaptation In Brain Metastasis
… nature, I performed an unbiased <em>in vivo</em> kinome screen to identify potential driver kinases of experimental brain metastasis in a nude xenograft model using the human breast cancer cell line MDA-MB-231. Several of the kinase pools led to decreased brain metastasis-specific survival in nude …
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High-throughput functionalization of the Toxoplasma kinome uncovers a novel regulator of invasion and egress
… gondii. To systematically examine the parasite kinome, we developed a high-throughput tagging (HiT) strategy to endogenously label protein kinases with an auxin-inducible degron and fluorophore. Hundreds of tagging vectors were assembled from synthetic sequences in a single reaction and used to …
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The discovery and anticancer preclinical investigation of novel piperazinylpyrimidine derivatives designed to target the human kinome
<p>The current dissertation describes a multidisciplinary research project centered on the discovery and investigation of the anticancer activities exhibited by novel piperazinylpyrimidine derivatives designed to target kinases protein family. Primary screening of the antiproliferative effects …
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Global characterization of oncogenic kinase signaling
… integrating mass spectrometry-based quantitative kinome profiling and siRNA-based functional genomics screens was applied to provide insights into this problem. Firstly, a novel broad-spectrum kinase inhibitor CTx-0294885 was developed and characterized as a kinase-capturing tool in order to …
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Investigating the role of the Hippo pathway in epithelial-mesenchymal transition and drug resistance
… thesis, I present two projects investigating the kinome signaling downstream of YAP and a survey of YAP-activity mediated changes to drug response. In the first project, I describe the first comprehensive survey of kinome signaling downstream of YAP. YAP hyper-activity results in widespread …
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Identification of cellular signaling events dysregulated in Huntington’s disease.
… complement of which is referred to as its kinome. The kinases responsible for driving the fate of phosphoproteomes are central to elucidating various complex cellular events. The interactive capacity of the phosphate group makes the phosphorylated protein versatile in communicating. The …
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Hear Today, Gone Tomorrow: Exploring Quinoxaline Derivatives as a Treatment for Noise-Induced Hearing Loss
… using an in silico ADME assay from SwissADME. A kinome activity assay was performed on organs of Corti to assess changes in kinase activity following noise exposure. We found that Qx34 and Qx62 had the most beneficial effects on noise-exposed animals; they recovered ABR and DPOAE thresholds the …
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Therapeutic Potential of Protein Kinases and Their Downstream Targets Following Traumatic Cervical Spinal Cord Injury
… work demonstrates the importance of targeted kinome-based therapeutics to alter the secondary response following traumatic SCI.
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Using Evolutionary Genomics to Elucidate Parasite Biology and Host-Pathogen Interactions
… source of functional innovation. The T. gondii kinome displays previously under-appreciated diversity in parasite-specific secreted kinases associated with the rhoptry organelles required for host cell invasion. Evolutionary analysis points to the importance of this ‘ROPK’ family, and functional …
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A comparative evaluation of the gastrointestinal immune response of the modern and heritage broiler chicken
… that received the treatment were subjected to kinome array analysis and compared to the same tissues from birds that received the control, a non-stimulatory oligonucleotide. The kinome array provides a real-time snapshot of kinase activity ongoing within the tissues in immune and metabolic …
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JAG1 Blockade With oHSV Polarizes Macrophages to Create a Unique Vulnerability for Cetuximab-Mediated Senolysis of Glioma Cells
… which relied on Notch signature in tumor cells. Kinome profiling revealed that OncoD-0J1 treatment suppressed CDK1, resulting in a G2/M cell cycle checkpoint as seen by cell cycle analysis. Cell cycle arrest led to senescence and correlated with increased reactive oxygen species, p62 …
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Developing Novel Therapies Targeting the Tumor Microenvironment of Aggressive Breast Cancer
… therapy, we conducted a synthetic lethal kinome siRNA screening in vitro to identify novel synergy targets. We found TANK-binding kinase 1 (TBK1) to be the top therapeutic candidate due to its critical role in immune responses. Strikingly, combined suppression of AXL and TBK1 significantly …
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Identification of the molecular pathways that mediate cytokine induced immunopathology of the gut epithelium
… by this cytokine combination. A human kinome RNAi screen and a drug repurposing screen identified the Janus kinases (JAKs) JAK1 and JAK2 as the major kinases required for IFN-γ + TNF-α dependent synergistic cell death. While TNF receptor-1 (TNFR1) was also required, there was no direct …
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Genetic and Chemical Genetic Approaches to Shiga Toxin Inhibition
… approach adapted a siRNA screen of the human kinome to a high-throughput format. In an effort to identify human kinases involved in Shiga toxin pathogenesis, we identified the mitogen-activated protein kinase-activated protein kinase 2: MK2) as a kinase involved in the host stress response to …
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The identification of the Tao-1 kinase as a key regulator of microtubule dynamics
… also revealed that, when considering the kinome, gene expression signatures are a poor measure of cell type specific differences in gene function, measured by comparing with the microarray data available in our lab. Most significantly, these screens identified a novel role for Mnb/DYRK1A, …
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Interaction Mapping of the Atypical Protein Kinase WNK3
… WNK1, they comprise an atypical branch of the kinome--the functions and significance of which are still being elucidated. Of clinical significance, WNKs 1 and 4 have been implicated in a heritable form of hypertension (pseudohypoaldosteronism type II). WNK3 has been reported to regulate certain …
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Simultaneous Targeting of CDK4/6 and BETs is Independent of RB Status in Osteosarcoma
… mechanistic profiling, using transcriptomic, kinome, and histologic analysis aim to refine combination strategies, optimize BETi dosing and sequencing, and define the contexts where dual CDK4/6i and BETi therapy most effectively limit OS progression and dissemination.
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Evaluation of Glycogen Synthase Kinase 3 as a drug target in African trypanosomes
… development or in the clinic. The T. brucei kinome has been annotated and there is evidence of essentiality of some of the members of this family. This thesis aims at evaluating the essentiality of Glycogen Synthase Kinase 3 (TbGSK3 short; Tb927.10.13780) and chemically validating it as a …
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