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 “"Cellular survival"”.
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Interrogating DNA replication stress and DNA damage responses via phenotypic and functional CRISPR/Cas9 screens
… a constant threat for genome integrity and cell survival. Consequently, various DNA repair processes and pathways have evolved to deal with different DNA lesions and ensure genome stability. The tumour suppressor ATM is one of the apical kinases in the DNA damage response (DDR), occupying a key …
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Structural and Functional Evolution of Human Heat Shock Transcription Factors
… our mechanistic understanding of the cellular response to proteotoxic stress is limited. A critical feature of the cellular stress response is the activation of Heat Shock Transcription Factors (HSFs) that regulate the expression of numerous genes involved in protein folding, protein …
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Modeling Brk/PTK6 expression in the mammary epithelium.
Protein tyrosine kinases (PTKs) regulate cellular proliferation and differentiation during development and homeostasis of normal tissues. Additionally, PTKs are frequently overexpressed in cancers. As such, they have become promising targets for new therapies. Breast tumor kinase (Brk/PTK6) is a …
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A novel role for the transcriptional modulator NusA in DNA repair/damage tolerance pathways in Escherichia coli
… repair and DNA damage tolerance are crucial for cellular survival after DNA damage. Translesion DNA synthesis (TLS) is one such mechanism of DNA damage tolerance which utilizes a specialized translesion DNA polymerase capable of catalyzing DNA synthesis on imperfect templates. There are two TLS …
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Structural Studies of Integral Membrane Proteins Involved in GPCR Signaling and Sterol Homeostasis
Membrane proteins are crucial molecules for cellular survival, and can take on multiple and diverse roles within the native membrane. In this dissertation, I will detail my efforts to understand and study two different types of membrane proteins. First, I will discuss my research developing and …
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DNA damage tolerance and mutagenesis : the regulation of S. cerevisiae Rev1
… information that ultimately may cause altered cellular functions, cell death, or uncontrolled growth as in the case of tumor cells. Fortunately, cells possess a multitude of mechanisms to ensure the fidelity of DNA replication and protect against permanent changes to DNA. These mechanisms …
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The role of mismatch repair and recombination in cellular responses to the DNA damaging anticancer drug Cisplatin
… illustrated that while recombination promotes cellular survival following cisplatin damage, mismatch repair, in contrast, promotes cisplatin toxicity. The mismatch repair protein MutS recognized cisplatin-DNA adducts with 2-fold higher affinity than adducts of oxaliplatin, a cisplatin analog …
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Regulation of FBP1 expression and changes in glucose metabolism are crucial for an appropriate response to DNA damage and aging in S.cerevisiae
… as the immediate cytotoxic effect. Therefore, cellular response to the treatment with DNA-damaging substances at low concentrations which are genotoxic but do not have a strong cytotoxic effect are of special interest. Investigating the transcriptional response of S.cereveisiae to low doses of …
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Modulated Functions of The Fanconi Anemia Core Complex
… effects on the activation of FA pathway and on cellular survival against ICLs. Our results suggest three potential functional modules in the FA core complex: FANCB-FANCL-FAAP100 (B-L-100), FANCA-FANCG-FAAP20 (A-G-20), and FANC-FANCE-FANCF (C-E-F). We showed that the B-L-100 sub complex is the …
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LINKING TRANSCRIPTIONAL AND MORPHOLOGICAL HETEROGENEITY TO THERAPEUTIC VULNERABILITIES IN GLIOBLASTOMA
… elicit a gene-independent detrimental effect on cellular survival when targeting genomic copy-number amplified regions (CN bias) and spurious effect due to Cas9-mediated whole chromosome arm truncations (proximity bias). Subsequently, I have focused on the integration of transcriptomics and …
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Targeting LEDGF/p75 to Sensitize Chemoresistant Prostate Cancer Cells to Taxanes
… resulting in activation of stress and prosurvival pathways contribute to disease progression and the development of chemoresistance. Lens epithelium-derived growth factor p75 (LEDGF/p75) is a stressresponse protein that promotes cellular survival against environmental stressors, including …
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The Pursuit of Unshocking Hsp90 Inhibitors: Development of Gedunin and Cruentaren A as Chemical Leads
… is a molecular chaperone that is critical cellular survival and growth under both typical and stressful conditions. Hsp90 is responsible for the maturation and stability of more than 200 client proteins involved in a diverse assortment of cellular processes. Disruption of Hsp90's …
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Characterization of Erbb4 Expression In Osteosarcoma
… as “p80,” which has been demonstrated to enhance cellular survival and malignant behavior in many solid tumors [44]. ERBB4 was almost exclusively 80 kDa in size and localized to the nucleus in primary tumors and metastases in studies characterizing ERBB4 expression in osteosarcoma, indicating that …
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Investigation of spermatozoal metabolism and substrate utilization in domestic and non-domestic felids
… causes diminished spermatozoal function and low cellular survival. The effects of cryopreservation are further compounded in spermatozoa from individuals with disorders known to affect fertility. Teratospermia, characterized by the ejaculation of >60% morphologically abnormal spermatozoa, is one …
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Tissue Salvage in the Non-reperfused Myocardium Mediated by (the absence of the circadian rhythm gene) mPer2 and (the receptor tyrosine kinase) EphrinA1
… at the time of MI would promote cardiomyocyte survival, subsequently reducing infarct size and inflammatory cell infiltrate. The ephrinA1 ligand has been predominantly characterized as a pro-angiogenic factor in development and tumor progression, but is also involved in apoptosis and …
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Design of selective peptide inhibitors of anti-apoptotic Bfl-1 using experimental screening, structure-based design, and data-driven modeling
… to short, pro-apoptotic BH3 motifs to support cellular survival. Overexpression of BfI-1 has been shown to promote cancer cell survival and the development of chemoresistance. Prior work suggests that selective inhibition of Bfl-1 can induce cell death in Bfl-1 overexpressing cancer cells …
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The protective role of tumour necrosis factor alpha in the heart
… signalling peptide which promotes myocyte cellular survival, in part, through activation of NFₖ B.
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Structural and biophysical analysis of Human DNA repair protein CtIP
… repair of DNA lesions is necessary for cellular survival and prevention of disease such as cancer. Therefore, complex molecular pathways have evolved to allow for accurate and timely DNA repair. It is now well-established that mammalian CtIP (CtBP-Interacting Protein) has an important …
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Defining Determinants of Primary Drug Resistance in Precision Cancer Therapies
… treatment approaches to improve patient survival outcomes are still lacking. Motivated by this unmet need, we performed drug sensitizer screens with a PI3K-alpha isoform-specific inhibitor, BYL719, in multiple PIK3CA wild-type (WT) and mutant cell lines, including those derived from …
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Molecular Mechanisms of Host Responses to Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Infection
… (SGs) during PRRSV infection. SGs are intracellular, cytoplasmic aggregates of RNA-binding proteins (RBPs) and mRNA. Formation of SGs is observed upon cellular stress and ultimately function to arrest cellular translation to promote cellular survival until the stress has been remedied. …
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