Sialylation Of Tnfr1 By St6gal1 Modulates Receptor Dynamics And Determines Cell Fate,
2025
University of Alabama at Birmingham
Sialylation Of Tnfr1 By St6gal1 Modulates Receptor Dynamics And Determines Cell Fate, Jihye Hwang
All ETDs from UAB
Abnormal glycosylation has long been identified as a key feature of cancer. Aberrant glycan structures on tumor cells arise from the dysregulation of select glycosyltransferases. For example, sialyltransferase ST6GAL1 is notable for its high expression in various cancers, including breast, colon, ovarian, and pancreatic. ST6GAL1 introduces α2-6-linkage sialylation to N-glycans on proteins, endowing cancer cells with stem cell-like properties. This modification contributes to resistance to apoptosis mediated by death receptors like TNFR1. Despite its significance in cancer, the regulatory mechanisms controlling ST6GAL1 expression remain largely unexplored. Additionally, it is unclear whether the apoptosis-resistant effect of sialylation is caused by an …
Characterizing The Molecular Complexities Of Iga1 By Serum Proteomics In The Context Of Iga Nephropathy,
2025
University of Alabama at Birmingham
Characterizing The Molecular Complexities Of Iga1 By Serum Proteomics In The Context Of Iga Nephropathy, Mary A. Cunningham
All ETDs from UAB
Immunoglobulin A1 (IgA1) is the second most abundantly produced immunoglobulin in circulation per day and plays a key role in human immunity. Two molecular complexities of IgA1 make accurately studying the protein challenging. The first is that IgA1 exists in three main molecular forms in the serum of humans: monomeric (mIgA1, 80-90% of serum IgA1), polymeric (pIgA1, 10-20% of serum IgA1), and IgA1-containing immune complexes (IgA1-IC, <0.5% of serum IgA1). The second complexity is that the hinge-region of IgA1 is extensively O-glycosylated and exhibits a high level of variation in its O-glycans, particularly in the degree of sialylation. In context of the autoimmune disease IgA nephropathy (IgAN), patients have elevated levels of IgA1 that has reduced levels of galactose (Gal) in the IgA1 hinge-region (Gal-deficient IgA1). This Gal-deficient IgA1 forms immune complexes with IgG autoantibodies (IgA1-IC), deposits in the glomeruli, and induces kidney injury. While it is established that these large IgA1-IC (>700 kDa) formed in the circulation are pathogenic, there remains a gap in knowledge about other blood proteins that may be associating with IgA1 in complexes. It is also necessary to understand the native …
Mechanistic Insights Of Translational Readthrough To Suppress Nonsense Mutations,
2025
University of Alabama at Birmingham
Mechanistic Insights Of Translational Readthrough To Suppress Nonsense Mutations, Kari Thrasher
All ETDs from UAB
A nonsense mutation is a point mutation in DNA that gives rise to a premature termination codon (PTC) in the open reading frame of the transcribed mRNA. Translation of this PTC-containing transcript terminates prematurely, leading to the creation of truncated non-functional protein. Translational readthrough is one therapeutic option being explored to suppress nonsense mutations that cause disease. Here, we further elucidate amino acid incorporation and the functional consequences of readthrough of nonsense mutations that cause cystic fibrosis. Additionally, we reveal the molecular mechanisms activated by a recently described small molecule readthrough agent, SRI- 41315. Finally, we discuss the various therapeutic …
Characterization Of The Roles Of U1-70k In Alternative Splicing And Nuclear Speckle Formation,
2025
University of Alabama at Birmingham
Characterization Of The Roles Of U1-70k In Alternative Splicing And Nuclear Speckle Formation, Trenton Myers Paul
All ETDs from UAB
RNA-binding proteins (RBPs) play critical roles in RNA processing and regulation. Among these RBPs, U1-70K is a key protein involved in RNA processing, nuclear speckle formation, and has implications in neurodegenerative diseases such as Alzheimer's. Despite its significance in transcription, RNA processing, nuclear speckle formation, and nonsense-mediated decay, studies on U1-70K have been limited primarily to its well-structured N-terminal domain due to challenges in solubilizing and expressing the full-length protein. In this dissertation, we address these challenges by optimizing cell strain and co expressing DnaK and DnaJ, enabling the successful expression, solubilization, and purification of full-length U1-70K. Using fluorescence polarization …
Controlled By Disorder: Modifications To An Unstructured C-Terminal Region Alter Srsf1'S Intramolecular Interactions And Tendency To Phase Separate,
2025
University of Alabama at Birmingham
Controlled By Disorder: Modifications To An Unstructured C-Terminal Region Alter Srsf1'S Intramolecular Interactions And Tendency To Phase Separate, Talia Fargason
All ETDs from UAB
The protein Serine-Arginine-rich Splicing Factor 1 (SRSF1) is essential in multiple stages of the mRNA lifecycle, including alternative splicing, nonsense-mediated decay, and nuclear export. SRSF1’s dysfunction is linked to cancers, viral evasion, and developmental disorders. Its function depends on interactions between structured and unstructured regions, modulated by phosphorylation. However, the unstructured regions, while critical for regulation, contribute to protein insolubility, hindering full-length studies. Prior to the work presented here, structural studies of SRSF1 were limited to analysis of its isolated domains. This dissertation develops new techniques to characterize SRSF1, focusing on its intermolecular interactions driving phase separation and intramolecular interactions …
Unraveling The Kinetic Mechanisms Of Protein Unfolding And Translocation Catalyzed By Hsp100 Unfoldases,
2025
University of Alabama at Birmingham
Unraveling The Kinetic Mechanisms Of Protein Unfolding And Translocation Catalyzed By Hsp100 Unfoldases, Jaskamaljot Kaur Banwait
All ETDs from UAB
Escherichia coli ClpB and Saccharomyces cerevisiae Hsp104 are part of the Hsp100 family of proteins responsible for maintaining protein homeostasis in a cell during heat-stress conditions. Structurally, ClpB and Hsp104, in their active state, assemble into hexameric ring complexes with a hollow axial channel. Functionally, these enzymes are hypothesized to couple energy from ATP binding and hydrolysis to unfold protein substrates and translocate them through their axial channel. However, the molecular mechanisms of protein unfolding and translocation catalyzed by both ClpB and Hsp104 are not well understood. In this dissertation, we report the development of a single-turnover transient state kinetics …
Optimizing Biofilm Assay Reproducibility And Characterizing The 12-Hydroxystearic Acid On Escherichia Coli,
2025
CUNY Hunter College
Optimizing Biofilm Assay Reproducibility And Characterizing The 12-Hydroxystearic Acid On Escherichia Coli, Khilola Khusanova
Theses and Dissertations
Biofilm formation in Escherichia coli plays a critical role in microbial chemical communication and surface-associated persistence. This study investigates the antibiofilm activity of 12-hydroxystearic acid (12-HSA), evaluating its R and S enantiomers as well as a racemic mixture. E. coli BL21, biofilms were grown under standardized laboratory conditions and quantified using the Crystal Violet staining assay. Treatment with 12-HSA resulted in a measurable reduction in biofilm biomass, with differences observed between the individual enantiomers and the mixture. These findings suggest that 12-HSA influences early adhesion and biofilm development, supporting its potential as a small-molecule modulator of bacterial surface behavior. This …
Nls-Binding Deficient Kapβ2 Reduces Neurotoxicity Via Selective Interaction With C9orf72-Als/Ftd Dipeptide Repeats,
2025
Thomas Jefferson University
Nls-Binding Deficient Kapβ2 Reduces Neurotoxicity Via Selective Interaction With C9orf72-Als/Ftd Dipeptide Repeats, Kevin Kim, Amandeep Girdhar, Maria Elena Cicardi, V. Kankate, Miyuki Hayashi, Ruoyu Yang, Jenny Carey, Charlotte M Fare, James Shorter, Gino Cingolani, Davide Trotti, Lin Guo
Department of Biochemistry and Molecular Biology Faculty Papers
Arginine-rich dipeptide repeat proteins (R-DPRs) are highly toxic proteins found in patients with C9orf72-linked amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). R-DPRs can cause toxicity by disrupting the natural phase behavior of RNA-binding proteins (RBPs). Mitigating this abnormal phase behavior is, therefore, crucial to reduce R-DPR-induced toxicity. Here, we use FUS as a model RBP to investigate the mechanism of R-DPR-induced aberrant RBP phase transition. We find that this phase transition can be mitigated by Kapβ2. However, as a nuclear import receptor and phase modifier for PY-NLS-containing RBPs, the function of WT Kapβ2 could lead to undesired interaction with its …
Investigating The Interactions Between Elm1 And Hsl7 In The Morphogenesis Checkpoint Of Saccharomyces Cerevisiae,
2025
Western Kentucky University
Investigating The Interactions Between Elm1 And Hsl7 In The Morphogenesis Checkpoint Of Saccharomyces Cerevisiae, Rachel Foster
Masters Theses & Specialist Projects
Cell shape is essential to understanding the normal regulatory processes that occur within the cell and can indicate there are abnormalities present when there is dysfunction in the cell's development, which can have broader implications regarding human disease. The morphogenesis pathway couples cell division to the timely formation of a daughter bud in Saccharomyces cerevisiae and consists of Elm1, Hsl1, Hsl7, and Swe1 proteins which interact with septins at the bud neck to provide stability for the bud and to facilitate cell division. Elm1 is needed for the recruitment of Hsl1 and subsequently Hsl7. Hsl7 will then tether Swe1 to …
Protein-Metal Interactions Of A-Synuclein And Bioactive Transition Metals Via Molecular Dynamics,
2025
Saint John's University, Jamaica New York
Protein-Metal Interactions Of A-Synuclein And Bioactive Transition Metals Via Molecular Dynamics, Gonzalo R. Vazquez
Theses and Dissertations
Parkinson’s Disease (PD) is a neurodegenerative movement disorder which has been found to target the dopaminergic neurons of the substantia nigra. It is characterized by the formation of masses known as Lewy Bodies, formed by aggregates of the intrinsically disordered protein (IDP) -synuclein (asyn). Research suggests that alpha synuclein can undergo aggregation in the presence of heavy metals, which may accumulate in the body through a variety of mechanisms. To study how metals may play a role in wildtype (WT) asyn aggregation, MD simulation of the protein was performed in the presence of bioactive transition metals including Fe2+, Fe3+, Cu+, …
Anti-Cancer Compounds Based On Natural Imidazole Compounds,
2025
Columbus State University
Anti-Cancer Compounds Based On Natural Imidazole Compounds, Autumn Forsythe, Victoria Hardy, Kerri L. Shelton
CSU Tower Day
We are developing a comprehensive review on imidazole-based compounds of natural origin, the most common groups of compounds, and their properties, such as the imidazole ring. The intent of this presentation is to learn about the compound’s occurrence, general/predicted properties, and advantages. The review will be a fluid development comparing imidazole derivatives of natural origin with antinociceptive/lethal properties from the last 5 years. This review would include both purely extracted products but also those modified by synthesis.
Characterization Of Legionella Pneumophila Effector Protein Ceg10,
2025
Western Kentucky University
Characterization Of Legionella Pneumophila Effector Protein Ceg10, Emmanuella Ofoka
Masters Theses & Specialist Projects
Legionella pneumophila, the causative agent of Legionnaires' disease, utilizes a Type IV secretion system (T4SS) to transport effector proteins into host cells. This bacterium is said to have over 300 effector proteins. Among these, the Ceg10 effector protein had remained uncharacterized, despite evidence suggesting the importance of bacterial effector proteins in the host-pathogen interaction. This study aimed to perform a structural and functional characterization of Ceg10 through transcriptomic, bioinformatics, and molecular analyses. Transcriptomic profiling of HEK 293T cells expressing Ceg10 revealed significant differential gene expression, with approximately 20 upregulated genes, including leucine-rich repeat, as well as other downregulated genes. …
Biological And Chemical Evaluation Of Amide-Based Cjoc42 Derivatives As Potential Gankyrin-Inhibitors For The Treatment Of Breast, Lung, And Liver Cancer,
2025
Saint John's University, Jamaica New York
Biological And Chemical Evaluation Of Amide-Based Cjoc42 Derivatives As Potential Gankyrin-Inhibitors For The Treatment Of Breast, Lung, And Liver Cancer, Benita Britton-George
Theses and Dissertations
Gankyrin is an ankyrin-repeat protein overexpressed in certain cancers and is responsible for cell growth and proliferation. Gankyrin is important to the development of many types of cancer, including breast, lung, and liver cancer. Consequently, gankyrin and its various protein-protein interactions, are prospective therapeutic targets for inhibiting the progression of certain cancers. In 2016, the first small molecule inhibitor of gankyrin, cjoc42, was discovered and subsequently demonstrated modest antiproliferative activity against liver cancer cells. Previous work from our lab demonstrated that replacing the sulfonate ester of cjoc42 with an amide group significantly improved gankyrin binding while enhancing antiproliferative activity against …
Expression And Function Of Floral Symmetry Genes In The Regulation Of Flower Shape In Fedia Graciliflora,
2025
Saint John's University, Jamaica New York
Expression And Function Of Floral Symmetry Genes In The Regulation Of Flower Shape In Fedia Graciliflora, Theresa A. Mustacchio
Theses and Dissertations
Shifts between radial symmetry (actinomorphy) and bilateral symmetry (zygomorphy) in flowers have occurred multiple times independently within angiosperms (flowering plants). Evidence across angiosperms indicate the transcription factors RADIALIS (RAD), DIVARICATA (DIV), and CYCLOIDEA (CYC) play a major role in regulating floral symmetry and morphology. The CYC-like genes have been shown to shift their expression dorsally independently in nearly all shifts to bilaterally symmetrical flowers examined. Three core eudicot clades of CYC-like genes have been identified: CYC1, CYC2 and CYC3, with only CYC2 genes being shown to have a role in floral symmetry. We use the non-model plant, Fedia graciliflora (Caprifoliaceae) …
Analysis Of The Influence Of Telomere Length Variation On Flowering Time And Plant Fitness In Arabidopsis,
2025
Marshall University
Analysis Of The Influence Of Telomere Length Variation On Flowering Time And Plant Fitness In Arabidopsis, Brianna Spadavecchia
Theses, Dissertations and Capstones
Telomeres are conserved structures at the ends of eukaryotic chromosomes that promote genome stability. In most eukaryotes, the DNA found within these protective end caps consists of short, G-rich nucleotide repeats. Cells with critically short telomeres face a variety of potential adverse outcomes such as end-to-end chromosome fusion, apoptosis, etc. The length of telomeric DNA varies substantially between different plant species and even between genotypes of the same species. A previous study using T-DNA mutants of the model plant Arabidopsis thaliana with long or short telomeres suggested that telomere length may be an adaptive trait. Specifically, for reproductive fitness, the …
Structural Impacts Of Canonical And Non-Canonical Oligonucleotide Modifications,
2025
Wayne State University
Structural Impacts Of Canonical And Non-Canonical Oligonucleotide Modifications, Deepak Shrestha
Wayne State University Dissertations
Nucleic acids, including DNA (deoxyribonucleic acid) and RNA (ribonucleic acids), are the fundamental building blocks of living organisms. The events that cause modification of DNA/RNA are of interest because they impact the nucleic acid function. Targeting DNA is important for treating diseases such as cancer. Cisplatin (cisPt) is a well-studied drug that targets DNA and blocks replication, but its use is limited by adverse side effects and cellular resistance. Prevoius research addressed some of these challenges through development of platinum analogues such as carboplatin and oxaliplatin. Amino acid-linked platinum analogues (AAPt) are the focus of this thesis work. AAPt complexes …
Mass Spectrometry Combined With Chemical Biology To Study Human Ailments,
2025
Wayne State University
Mass Spectrometry Combined With Chemical Biology To Study Human Ailments, Eric Thomas Jacquerio Davis
Wayne State University Dissertations
Post-translational modifications (PTMs) are essential as chemical changes that regulate protein function, activity, stability, interactions, and localization after protein synthesis. PTMs, such as phosphorylation, acetylation, and ubiquitination, can activate or deactivate proteins, influence their interactions with other molecules, and determine their cellular location. This regulation is vital for numerous biological processes, such as cell cycle control, signal transduction, and gene expression. Abnormal PTMs are linked to various diseases in humans, including parasitic infection, blood disorders, cancers, and neurodegenerative diseases, making their study crucial for understanding disease mechanisms and developing targeted therapies. In the Pflum lab, we are interested in the …
Ashwagandha And Sexual Health In Women With Hypoactive Sexual Desire Disorder: Exploring Extent Of Adaptogenic Properties,
2025
Virginia Commonwealth University
Ashwagandha And Sexual Health In Women With Hypoactive Sexual Desire Disorder: Exploring Extent Of Adaptogenic Properties, Rhea Chatterjee
AUCTUS: The Journal of Undergraduate Research and Creative Scholarship
Hypoactive Sexual Desire Disorder (HSDD) affects 40% of women and potentially decreases their quality of life. Currently, the primary treatment for HSDD is Flibanserin, which is a serotonergic agonist and an antidepressant. However, the limited efficacy of Flibanserin encourages the exploration of the utilization of traditional drugs such as Withania somnifera, otherwise known as Ashwagandha, as an alternative treatment for HSDD. Minimal studies examine ayurvedic medications or the symptoms of illnesses that traditional Western medicines are unable to treat. This comprehensive literature review investigated the efficacy of Ashwagandha in improving sexual function in women with HSDD. The paper evaluated …
Identifying The Constituents Of Pyrolysis Oil Using Supercritical Fluid Chromatography- Fraction Collection (Sfc-Fc) And Gas Chromatography- Mass Spectrometry/Vacuum Ultraviolet Spectroscopy (Gc-Ms/Vuv),
2025
University of Texas at Arlington
Identifying The Constituents Of Pyrolysis Oil Using Supercritical Fluid Chromatography- Fraction Collection (Sfc-Fc) And Gas Chromatography- Mass Spectrometry/Vacuum Ultraviolet Spectroscopy (Gc-Ms/Vuv), Sadid Morshed
2025 Fall Honors Capstones Projects - Archive
Plastic waste continues to accumulate as production increases and disposal methods remain insufficient. Even with recycling programs in place, much of the discarded plastic still ends up in landfills or waterways, eventually breaking down into harmful microplastics. One promising solution is the conversion of plastic waste into pyrolysis oil, which can also serve as an alternative feedstock for chemicals. Pyrolysis oil is produced by heating plastics to approximately 800 °C in the absence of oxygen, resulting in a complex mixture of hydrocarbons that includes paraffins, isoparaffins, olefins, naphthenes, and aromatics. Analyzing the amount of oxygen, nitrogen, and sulfur in these …
Cdh-3/Cadherin, Yap-1/Yap And Egl-44/Tead Promote Syx-2/Syntaxin And Eff-1 Fusogen-Mediated Phagosome Closure,
2025
University of Texas at Arlington
Cdh-3/Cadherin, Yap-1/Yap And Egl-44/Tead Promote Syx-2/Syntaxin And Eff-1 Fusogen-Mediated Phagosome Closure, Alec Whited, Aladin Elkhalil, Ginger Clark, Piya Ghose
Biology Theses - Archive
Physical interactions between cells, such as cell-cell junctions, can profoundly impact cell fate. A vital cell fate for normal development and homeostasis is programmed cell death. Cells fated to die must be efficiently cleared away via phagocytosis, and defects are associated with a variety of diseased states. Whether cell-cell physical associations affect programmed cell elimination has not been well-explored. Here we describe, in vivo, a cell-cell adhesion-driven signaling pathway that ensures compartment-specific cell clearance during development. We previously described the specialized cell death program “Compartmentalized Cell Elimination” (CCE) in the C. elegans embryo. During CCE, the tail-spike cell (TSC), a …
