Molecular Biology Commons^™

Combination Of 64/67cu Theranostics And Immunotherapy Targeting Fibroblast Activation Protein In Triple Negative Breast Cancer, Fnu Sharmila Sridhar

All ETDs from UAB

Triple negative breast cancer (TNBC) makes up 10-20% of breast cancer cases. Even with advancements in science, TNBC is treatment resistant due to the lack of any type of hormonal receptors on the cell surface making it difficult for targeted hormonal therapy. New research avenues have led to studies of the Tumor-microenvironment (TME) in detail. TME is a complex network of stromal cells, extracellular matrix (ECM) and cancer associated fibroblasts (CAFs) with pro-tumorigenic properties and plays a major role in tumor growth. Fibroblast activation protein (FAP) is a marker of CAF and promotes ECM remodeling through several pathways and has …

Biologic Evaluation Of 64cu & 67cu As Potential Theranostic Agents For Cancer Radiotherapy, Lakshmi Madhusoodanan

All ETDs from UAB

Immunotherapy has become a mainstay in the treatment of several types of cancer, with the potential to induce durable remission, albeit in a limited percentage of patients. More recently, radiopharmaceuticals have gained recognition in cancer treatment due to their ability to localize within cancer cells and deliver radiation, reducing adverse effects precisely. Cancer radiotherapy has the potential to synergize with immunotherapy due to its induction of immunogenic cell death (ICD), which results in distinct cellular injuries such as the formation of single-strand breaks (SSBs) and double-stranded breaks (DSBs), disruption of mitochondrial integrity, and the excessive generation of reactive oxygen species …

Determination Of Readthrough Susceptibility Among Different Schwann Cell Lines Carrying Nonsense Mutations, Trushali Vansadia

All ETDs from UAB

Neurofibromatosis Type 1 (NF1) is a genetic disorder that affects the nervous system through the formation of tumors or neurofibromas. Encoded by the NF1 gene, neurofibromin functions as a tumor suppressor by converting active GTP-Ras to inactive GDP-Ras. 20% of NF1 patients carry a genomic nonsense mutation, which generates a premature termination codon (PTC) in the NF1 mRNA, leading to the formation of a truncated neurofibromin protein. Termination at PTCs can be suppressed by the incorporation of an amino acid at the site of the PTC, also known as readthrough. Readthrough results in continued translation elongation downstream of the PTC …

Serum Proteomic Profile Of Subclinical Babesia Bovis Infection In Pcr-Positive Eld's Deer Using Serum Protein Electrophoresis Coupled With Lc-Ms/Ms, Vichayanee Pumpitakkul, Sittiruk Roytrakul, Narumon Phaonakrop, Gunnaporn Suriyaphol Assoc. Prof.

The Thai Journal of Veterinary Medicine

Subclinical babesiosis observed in captive Eld’s deer, which act as reservoirs for ticks, poses a risk to healthy herds. However, the knowledge of biomarkers for subclinically infected Eld’s deer and host-parasite interactions is limited. This study aimed to investigate the serum proteomic profiles and protein interactions of Babesia bovis and subclinically infected Eld’s deer, PCR-positive for B. bovis, using automated serum protein electrophoresis and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The findings revealed albumin and four globulin fractions: alpha-1, alpha-2, beta, and gamma globulin. Albumin protein (ALB) was consistently detected across all fractions, highlighting its role in maintaining osmotic balance …

Developing Coexpression Systems To Introduce Hydroxyproline Into Protein Engineered Collagen Peptides Utilizing Hydroxylase From Acanthamoeba Polyphaga Mimivirus, Jennifer Soldatich

Theses and Dissertations

A major challenge of developing collagen mimetic peptides (CMPs) by bacterial expression is to include hydroxyproline for biomedical applications. Coexpression of Prolyl-4-hydroxylase from A.mimivirus with CMPs was investigated. Additionally, four expression designs were created for potential applications in mammalian cells to utilize their natural ability of proline-hydroxylation by post-translational modification.

Predicting The Association Of Metabolites With Both Pathway Categories And Individual Pathways, Erik D. Huckvale, Hunter Moseley

Markey Cancer Center Faculty Publications

Metabolism is a network of chemical reactions that sustain cellular life. Parts of this metabolic network are defined as metabolic pathways containing specific biochemical reactions. Products and reactants of these reactions are called metabolites, which are associated with certain human-defined metabolic pathways. Metabolic knowledgebases, such as the Kyoto Encyclopedia of Gene and Genomes (KEGG) contain metabolites, reactions, and pathway annotations; however, such resources are incomplete due to current limits of metabolic knowledge. To fill in missing metabolite pathway annotations, past machine learning models showed some success at predicting the KEGG Level 2 pathway category involvement of metabolites based on their …

Noise Leads To The Perceived Increase In Evolutionary Rates Over Short Time Scales, Brian C. O'Meara, Jeremy M. Beaulieu

Biological Sciences Faculty Publications and Presentations

Across a variety of biological datasets, from genomes to conservation to the fossil record, evolutionary rates appear to increase toward the present or over short time scales. This has long been seen as an indication of processes operating differently at different time scales, even potentially as an indicator of a need for new theory connecting macroevolution and microevolution. Here we introduce a set of models that assess the relationship between rate and time and demonstrate that these patterns are statistical artifacts of time-independent errors present across ecological and evolutionary datasets, which produce hyperbolic patterns of rates through time. We show …

Diverse Origins Of Near-Identical Antifreeze Proteins In Unrelated Fish Lineages Provide Insights Into Evolutionary Mechanisms Of New Gene Birth And Protein Sequence Convergence, Nathan Rives, Vinita Lamba, C.H. Christina Cheng, Xuan Zhuang

Biological Sciences Faculty Publications and Presentations

Determining the origins of novel genes and the mechanisms driving the emergence of new functions is challenging yet crucial for understanding evolutionary innovations. Recently evolved fish antifreeze proteins (AFPs) offer a unique opportunity to explore these processes, particularly the near-identical type I AFP (AFPI) found in four phylogenetically divergent fish taxa. This study tested the hypothesis of protein sequence convergence beyond functional convergence in three unrelated AFPI-bearing fish lineages. Through comprehensive comparative analyses of newly sequenced genomes of winter flounder and grubby sculpin, along with available high-quality genomes of cunner and 14 other related species, the study revealed that near-identical …

Understanding The Mystery Of R-Loops And Their Relationship To Nucleolar Stress, Kevin Shane

Master's Theses

Genomic instability is an increase in the likelihood of DNA mutations and genetic changes during cell division, a common feature in cancer cells. One cause of genomic instability comes from the aberrant formation of three-stranded nucleic acid structures called R-loops. R-loop form when an RNA strand hybridizes to its complementary strand of DNA, forming a stable RNA:DNA hybrid and displacing one free strand of DNA 1. Accumulation of unscheduled R-loops can lead to replication stress, fork collision, gene expression changes, and double-strand breaks that are underlying causes of genome instability and the development of many diseases, including cancer 2. Many …

Regulation Of P21 Function By A Sense Long Non-Coding Rna Generated By Alternative Polyadenylation, Anthony Ramadei

Dissertations, Theses, and Capstone Projects

As cells are continually undergoing damage to the genome, a coordinated change in gene expression across thousands of genes is required for the progression of the DNA damage response (DDR). After initial sensing of DNA damage, the transcription factor p53 induces expression of target genes to halt the cell-cycle to allow DNA repair and induce either senescence or apoptosis. One of the p53 target genes is CDKN1A which encodes the cyclin dependent kinase inhibitor p21. p21 halts cell-cycle progression in response to DNA damage and can also induce senescence. However, p21 expression in cancer cells undergoing chemotherapy allows survival by …

Retinoblastoma Malignance And Exosome Mechanisms Facilitating Optic Nerve Head Metastatic Niche Formation, Cui Shi

Dissertations, Theses, and Capstone Projects

Retinoblastoma (RB) is a rare pediatric ocular tumor that occurs before five years of age and it is the most common intraocular cancer of childhood with more than 300 children in the United States and 8000 diagnosed globally each year. RB arises from the proliferation of cone photoreceptor precursor cells in the retina as a result of mutations in the RB1 gene. The influence of RB secreted factors on cells in the retinal environment has not been fully elucidated. Cancer cell released exosomes have been shown to transform their microenvironment through transfer of metastasis promoting molecular cargo. Cancer cell extracellular …

Voltage Set Points For Sodium Channel Inactivation: Intrinsic And Modulatory Mechanisms, Akshay Sharma

Dissertations, Theses, and Capstone Projects

During an action potential, voltage-gated sodium channels (VGSC) control sodium ion flow into the cytoplasm of cells by using membrane voltage to alter channel conformation. These membrane proteins exhibit three main functional conformations: closed, open, and fast-inactivated, with transitions between these states dependent on membrane voltage and kinetics. The channels open within 1 millisecond and swiftly transition from open to fast-inactivated within 1-2 milliseconds following membrane depolarization. Subsequent membrane repolarization resets the channels to the closed state. Notably, even at mildly depolarized potentials that preclude channel opening, VGSCs can undergo transitions between the closed and inactivated states, known as closed-state …

Guardians Of The Bacterial Genome: Mechanistic Insights Of The Ner Atpase Uvra With Damaged Dnas; Molecular Interactions Between The V.Cholerae Initiator Rctb With Cognate Oricii Dna, Devon Semoy

Dissertations, Theses, and Capstone Projects

Nucleotide excision repair (NER) is one of the fundamental DNA repair pathways in all organisms. A unique facet of NER is the large set of DNA lesions the pathway is capable of repairing (Truglio, Croteau, et al. 2006). The NER proteins may thus be responding to global features of native DNA such as changes in thermodynamic stability, geometry and kinetic properties (Maillard et al. 2007). In this study we set out to investigate the first and primary responder to NER in bacteria, UvrA (Kraithong et al. 2021). UvrA is a homo-dimeric ABC ATPase; proteins that are known to transduce the …

The Seat Of Singular Gene Choice: Dissecting The Role Of Odorant Receptor Enhancer Elements That Lead To Mammalian Olfactory System Expression, Alessandro M. Rosa

Dissertations, Theses, and Capstone Projects

Odorant receptors (ORs) were first identified in 1991 and the initial data strongly suggested that ORs were part of a large superfamily of G-protein-coupled receptors. Within a few years of the discovery of the OR superfamily, it became clear that each OR allele was exclusively expressed in olfactory sensory neurons (OSN), and that this singular expression leads to cellular identity. Many studies over the past thirty years have sought to unlock the mysteries of the mechanism for monoallelic and monogenic OR gene activation and expression in OSNs, however no definitive model for singular gene expression has emerged.

Using a series …

Pm2.5 In The Respirable Air A Threat To Heart Health Investigating The Influence On Cardiovascular Performance And Unmasking The Potential Strategies For Cardio Protection, Bhavana Sivakumar

Theses and Dissertations

Air pollution, characterized by the presence of harmful substances in the atmosphere, represents a significant environmental and public health challenge impacting millions worldwide. The World Health Organization (WHO) reports that approximately 90% of the global population resides in regions where air pollution surpasses the recommended thresholds for healthy air quality. Within the realm of air pollution, the composition of particulate matter emerges as a pivotal consideration, particularly regarding PM2.5, comprising minute particles originating from diverse sources such as combustion processes, industrial operations, and natural phenomena like wildfires and dust storms. PM2.5 exhibit a range of chemical and physical attributes contingent …

Heparan Sulfate Roles In Amyloid-Beta Clearance And Alzheimer’S Disease Pathogenesis, Ilayda Ozsan

USF Tampa Graduate Theses and Dissertations

Alzheimer's disease (AD) is the most common form of dementia yet remains without an effective treatment due to its poorly understood etiology. Mounting evidence points to the accumulation and aggregation of amyloid-β peptides (Aβ), which constitute amyloid plaques in the brain, as pivotal in initiating and accelerating AD pathogenesis. Extensive efforts have focused on uncovering the molecular underpinnings and fundamental origins of impaired Aβ metabolism in AD. Heparan sulfate (HS), a linear polysaccharide of the glycosaminoglycan family, co-deposits with Aβ in plaques within the AD brain. It directly binds to and accelerates Aβ aggregation, interacts with key players in Aβ …

Emerin Deficiency Drives Mcf7 Cells To An Invasive Phenotype, Emily Hansen, Christal Rolling, Matthew Wang, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

During metastasis, cancer cells traverse the vasculature by squeezing through very small gaps in the endothelium. Thus, nuclei in metastatic cancer cells must become more malleable to move through these gaps. Our lab showed invasive breast cancer cells have 50% less emerin protein resulting in smaller, misshapen nuclei, and higher metastasis rates than non-cancerous controls. Thus, emerin deficiency was predicted to cause increased nuclear compliance, cell migration, and metastasis. We tested this hypothesis by downregulating emerin in noninvasive MCF7 cells and found emerin knockdown causes smaller, dysmorphic nuclei, resulting in increased impeded cell migration. Emerin reduction in invasive breast cancer …

Antimicrobial Studies Of Novel Pyrazole And Thiazole-Based Antibacterial Agents, Hansa Raj Kc

Student Theses and Dissertations

In recent years, the rise of antibiotic-resistant bacteria has become a global concern, resulting in fewer effective antibiotics. Several conventional antibacterial agents are ineffective against these, necessitating novel molecules with enhanced efficacy and diverse actions. We developed pyrazole and thiazole-based antibacterial agents and demonstrated that they have significant potency (minimum inhibitory concentration as low as 0.39 µg/mL) against antibiotic-resistant and susceptible bacteria, as well as promising anti-biofilm and anti-persister activity. In vivo toxicity tests on Caenorhabditis elegans showed no significant harm to this model host organism at low compound concentrations. These compounds rescued C. elegans from methicillin-resistant Staphylococcus aureus (MRSA) …

Unraveling The Role Of Hid-1: Insights Into Sgii Regulation, Breanna L. Sellers

Electronic Theses and Dissertations

The regulated secretory pathway is important for the secretion of hormones and neuropeptides from large dense core vesicles (LDCVs). Dysregulation of the biogenesis of LDCVs can result in metabolic and neurological diseases. Recent studies have suggested that the peripheral membrane protein HID-1 plays a role in the sorting and storage of granins which contribute to LDCV biogenesis. To further understand how HID-1 influences the regulation of granins, we investigated potential HID-1 interactors. We determined that while HID-1 is likely functioning in the same pathway as USP25, a deubiquitinating enzyme (DUB), the cause of reduced cellular SgII levels is likely not …

Sequence Specificity Of Non-Structural Protein 15 From Sars-Cov-2, John Vincent Mcguire

Electronic Theses and Dissertations

The SARS-CoV-2 virus was recently able to cause a global pandemic, largely due to the asymptomatic period that occurs during initial infection. During this period, patients are infectious but do not exhibit symptoms, resulting in the unintentional spread of the virus. This occurs because the virus effectively avoids detection by the immune system during the early stages of infection, and as symptoms are the result of immune system activation, they never manifest. Non-structural Protein 15 (Nsp15) is one of the tools the virus uses to remain undetected, via its degradation of Pathogen-Associated Molecular Patterns (PAMPs) that would otherwise be recognized …