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.
Results
Showing 1 to 20 of 78 for “"Therapeutic development"”.
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Financial and Analytic Innovations for Therapeutic Development
… laboratory discoveries to safe and effective therapeutics approved by the Food and Drug Administration (FDA) has become longer, more expensive, and less likely to succeed. As a result, there is a widening gap in financing the clinical development of novel drug candidates, preventing …
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Linking Biomolecular Condensates to Disease and Therapeutic Development
… examines biomolecular condensates in disease and therapeutic development. We find that condensate-promoting features in condensate-forming proteins can be mapped and leveraged to build a resource cataloging mutations that likely contribute to condensate dysregulation in human diseases (Banani et …
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Identifying and Inhibiting Cholesterol-Protein Interactions for Therapeutic Development
… and inflammatory bowel disease and develop new therapeutics designed to target specific cholesterol-protein interactions. First, we introduce a new method using Turbo ID proximity labeling paired with site-specific modulation of the cholesterol concentration to identify new cholesterol-protein …
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Pathogenic Characterization and Therapeutic Development for Fiblrolamellar Hepatocellular Carcinoma
… my research on developing the first systemic therapeutic for FLC, by targeting this mutation. I will show how I began by targeting the protein, which proved difficult given the similarities of the mutated protein to the wild-type protein. Then, I will discuss my work on developing an …
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Approaches towards therapeutic development against chronic brucellosis in a mouse model
… dissertation, with an aim to develop a better therapeutic against Brucella infection in mice. First, to overcome the cell membrane barriers, drug loaded nanoparticles were tested to treat B. melitensis infection in mice. Gentamicin loaded block-ionomer complexes (BICs) and magnetite …
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Leveraging cellular models of polycystic kidney disease for mechanistic discovery and therapeutic development
… kidney organoids for mechanistic and therapeutic studies of PKD. In our kidney organoid model, we utilize CRISPR base editing to generate human pluripotent stem cells with specific clinically documented patient mutations. This system elicits a robust cystic phenotype and allows …
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Physical consequences of natural and synthetic post-translational modifications
… endow diverse chemical and biological functions. Development of new modifications, control over extant, and the appreciation of their consequences promises to unveil the mechanisms of disease, provide avenues of therapeutic development, and provide insight into intricacies of life. As a result, …
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Directed evolution in human cells via adenoviral replication
… for both basic biological research, and therapeutic development. Typically, researchers turn to directed evolution either in vitro, in bacteria, or in yeast, to mutate, select, and amplify biomolecules of interest (BOls) with new and highly-tailored activities. Unfortunately, BOIs evolved …
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KDM4D Overexpression Enhances Cardiac Regeneration and Mitigates Myocardial Damage in Response to Ischemic Injury
… cardiac muscle after injury and prevent the development of heart failure has eluded the field for decades. We recently reported that lysine demethylase KDM4D could partially prevent and reverse cell cycle gene silencing, resulting in modest adult cardiac myocyte proliferation. In this study, …
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The Impact Of The Inhibitory Neuromodulator Agmatine On Microglia Function In The Contexts Of Pain And Addiction
… pain crisis highlight the urgent need for the development of novel, non-opioid, therapeutics to treat these diseases. The work presented in this dissertation aims to contribute to this solution through the evaluation of mechanistic properties of agmatine, an inhibitory neuromodulator in …
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Exploring Risk Factors of Alzheimer’s Disease Using Mouse Models
… understanding disease mechanisms and subsequent therapeutic development. We examined five commonly used mouse models of AD (5xFAD, J20, APPNL-F, APPNL-G-F, Tau P301S) and compared their whole- and phosphoproteomes with human AD (the integration of three published datasets) to study whether they …
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Giardia Cathepsins and Their Role in Intestinal Disease
… of these proteases may pave the way for therapeutic development.
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Disordered Protein Aggregates Are Linked to Changes in the Histone Post-Translational Modification Landscape in Disease and Non-Disease Models
… and potentially reveal novel targets for therapeutic development. Our results highlight a need for further research into how misfolded protein aggregates disrupt the histone PTM landscape. We hope this work will lead to the discovery of novel targets for neurodegenerative disease …
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Computational modeling of protein-biomolecule interactions with application to mechanotransduction and antibody maturation
… fundamental knowledge and as a foundation for therapeutic applications and biotechnology. This thesis presents two applications of computational modeling to study protein-biomolecule binding in different contexts. First, we sought to characterize effects of applied mechanical force on protein …
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Dissecting the Role of Novel O-GlcNAcylation of NF-κB in Pancreatic Cancer
… great promise for PDAC diagnosis and effective therapeutics. Here, we report a novel finding that the p65 subunit of NF-κB is O-GlcNAcylated at serine 550 and 551 upon NF-κB activation. Importantly, the overexpression of either serine-to-alanine (S-A) single mutant (S550A or S551A) or double …
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Targeting S1PR3 to mitigate flow-enhanced invasion in the glioblastoma tumor microenvironment
… To this end, we sought to identify additional therapeutic candidates mediating flow-enhanced invasion. Our previous work established a role for the G-protein coupled receptor S1PR3 in enhancing invasion under flow. Interestingly, we found this response to be mediated by the brain parenchymal …
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Exploring the Potential use of TEAD Inhibition as Part of a Combination Therapy for NF2-Deficient Schwannoma and Meningioma.
… cancer predisposition syndrome, resulting in the development of schwannoma, meningioma and ependymoma tumours. Although surgical resection and adjuvant radiotherapy can be used, new avenues of therapeutic development are essential to target inoperable and recurrent tumours. Previous studies …
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Understanding neurodegenerative disease-relevant molecular effects of perturbagens using a multi-omics approach
… are dysfunctional in these diseases is key for therapeutic development. Chemical and genetic perturbagens can probe cellular pathways to shed insight about both disease etiology and potential therapeutic targets. We analyzed the functional effects of chemical perturbagens in neurodegenerative …
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Use of the Protein Misfolding Cyclic Amplification for food safety and drug discovery
… raises public health concerns. Additionally, therapeutic strategies for prion diseases remain limited. This thesis presents a methodological exploration of the Protein Misfolding Cyclic Amplification (PMCA) technique to address these challenges in two key areas: (1) detecting CWD prions in …
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Design, synthesis, and biological activities of small molecules that target myotonic dystrophy
… in various disease phenotypes. As such, therapeutic development for DM has mainly focused on agents targeting the CUGexp/CCUGexp -MBNL1 interaction. This dissertation focuses on the development of rationally designed small molecules that target CUGexp and CCUGexp, including their …
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