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St6gal-I Mediated Sialylation Promotes Pancreatic Ductal Adenocarcinoma Progression And Chemoresistance, Asmi Chakraborty Jan 2019

St6gal-I Mediated Sialylation Promotes Pancreatic Ductal Adenocarcinoma Progression And Chemoresistance, Asmi Chakraborty

All ETDs from UAB

ST6Gal-I adds α2-6 sialic acids to select N-glycosylated cell surface receptors, thereby modulating receptor function and intracellular signaling. ST6Gal-I is upregulated in various carcinomas and confers cancer stem cell (CSC) properties evidenced by tumorspheroid growth, chemoresistance and tumor initiating potential. In pancreatic ductal adenocarcinoma (PDAC), ST6Gal-I conferred gemcitabine resistance by abrogating DNA damage and altering expression levels of gemcitabine metabolism genes. Further, ST6Gal-I promoted resistance to chronic gemcitabine treatment. Additionally, metastatic clones of a PDAC cell line had increased ST6Gal-I expression and ST6Gal-I knockdown enhanced gemcitabine sensitivity. To investigate the physiological consequences of ST6Gal-I in PDAC, murine models were used. …


The Role Of Protein O-Glcnacylation In Regulating Mitochondrial Function, Jalessa Nicole Wright Jan 2019

The Role Of Protein O-Glcnacylation In Regulating Mitochondrial Function, Jalessa Nicole Wright

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The attachment of O-linked-N-acetylglucosamine (O-GlcNAc) to the serine/threonine residues of proteins has emerged as an important regulatory mechanism in transcriptional regulation, protein activation as well as cell survival. Several studies have reported that elevated O-GlcNAc levels have adverse effects on mitochondrial function. These negative effects have been linked to O-GlcNAc modification of mitochondrial proteins that are integral across multiple metabolic cell processes i.e. VDAC, NDUFA9 and DRP-1. Mitochondrial complexes I, III and IV all contain subunit proteins that are O-GlcNAc modified and increased O-GlcNAcylation of these proteins is associated with deficits in oxidative phosphorylation in these models. Conversely, it has …


Pannexin 1 Channel Inhibition To Prevent Triggered Arrhythmia, Grace Elizabeth Salzer Jan 2019

Pannexin 1 Channel Inhibition To Prevent Triggered Arrhythmia, Grace Elizabeth Salzer

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The mechanism of triggered arrhythmia generation involves inappropriate diastolic calcium (Ca2+) releases from the sarcoplasmic reticulum that promote membrane depolarization when the released Ca2+ is transported out of the cardiomyocyte via the sodium Ca2+ exchanger (NCX). If membrane depolarization is large enough, these events can trigger an ectopic action potential. However, it is not fully understood what physiological factors facilitate triggered events at the tissue level. Pannexin 1 (Px1), a large transmembrane conductance channel, can be activated by various stimuli including increases in intracellular Ca2+. We predict that during diastolic Ca2+ releases, Px1 becomes activated and together with the NCX, …


Transcriptional Dynamics Of Dopaminergic Signaling, Katherine Elizabeth Savell Jan 2019

Transcriptional Dynamics Of Dopaminergic Signaling, Katherine Elizabeth Savell

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Drugs of abuse increase dopamine concentrations in the nucleus accumbens, a key reward structure that integrates contextual and cue-related information and regulates motivated behavior. This surge of dopamine triggers cell signaling cascades that converge in the nucleus to cause changes in gene expression, which are thought to lead to the observed functional and structural alterations in the reward circuit after exposure to drugs of abuse. However, while various drugs of abuse cause transcriptional changes, previously available tools have not had the capacity to deeply characterize these gene programs. Therefore, we optimized a dual lentivirus CRISPR system for targeted gene modulation …


Kidney Resident Macrophages Utilize Developmental Programming During Healing From Acute Kidney Injury, Jeremie Matthew Peabody Lever Jan 2019

Kidney Resident Macrophages Utilize Developmental Programming During Healing From Acute Kidney Injury, Jeremie Matthew Peabody Lever

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Acute kidney injury (AKI) can be a devastating condition, affecting up to sixty percent of critically ill patients in the United States. Despite the fact that AKI is associated with an increased risk of chronic kidney disease (CKD) and mortality, there are no targeted therapies available to treat it. Kidney resident macrophages (KRM) are likely necessary for healing and resolution of animal models of AKI. However, there remains a gap in knowledge regarding how KRM effect this function. The purpose of my thesis was to elucidate lineage relationships and functionally relevant adaptations of KRM and monocyte-derived mononuclear phagocytes (infiltrative MP) …


Structural And Functional Insights Into Influenza A Virus Ns1-Mediated Rig-I Antagonism, Alexander Jureka Jan 2019

Structural And Functional Insights Into Influenza A Virus Ns1-Mediated Rig-I Antagonism, Alexander Jureka

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The influenza virus non-structural protein 1 is well known to antagonize the host innate immune response through its interaction with the innate immune sensor, retinoic acid induc-ible gene I (RIG-I). While the complete mechanism of the NS1:RIG-I interaction remains unclear, we were the first to demonstrate a direct interaction between the NS1 RNA-binding domain (NS1RBD) from the 1918H1N1 influenza virus and the second caspase activa-tion and recruitment domain (CARD2) of RIG-I using NMR. In addition, we also identi-fied that mutation of Arg 21 in the 1918H1N1 NS1RBD to Gln (R21Q) completely abrogated the NS1:CARD2 interaction. Given that CARD2 plays a …


Mechanisms Of Acute Kidney Injury: The Role Of Ferritin Heavy Chain In Renal Heme-Unology, Laurence Marie Black Jan 2019

Mechanisms Of Acute Kidney Injury: The Role Of Ferritin Heavy Chain In Renal Heme-Unology, Laurence Marie Black

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The kidneys are complex, multi-faceted organs that are responsible for regulatory processes, such as fluid homeostasis, hormone production, blood pressure regulation, and systemic toxin removal. Sudden disruption of these processes by acute kidney injury (AKI) causes rapid decline in renal function as well as significant morbidity and mortality. AKI is a significant clinical concern, affecting up to 13.3 million people globally each year and has the propensity to progress to chronic kidney disease (CKD), though the mechanism remains undefined. One reason for this is due to the lack of understanding of models used to study both AKI and CKD, hindering …


Marcks Effector Domain: Functions In Glioblastoma Progression And Novel Cytolytic Therapy, Nicholas James Eustace Jan 2019

Marcks Effector Domain: Functions In Glioblastoma Progression And Novel Cytolytic Therapy, Nicholas James Eustace

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Glioblastoma (GBM; grade IV astrocytoma) is the most common primary adult brain malignancy and remains incurable despite tremendous advances in our understanding of this heterogeneous disease. In this dissertation, we explore the challenges encountered in the treatment of GBM and discuss a promising new therapeutic approach gleaned from studies of the phospholipid binding “effector” domain (ED) of the protein Myristoylated alanine-rich protein C kinase substrate (MARCKS). Following an introduction to central nervous system (CNS) tumors and the grading of diffuse gliomas, we explain how recent advancements to our understanding of the cellular and molecular composition of CNS tu-mors, and the …


Modulation Of Klotho Affects Dendritic Spine Remodeling And Neuronal Network Activity, Hai T. Vo Jan 2019

Modulation Of Klotho Affects Dendritic Spine Remodeling And Neuronal Network Activity, Hai T. Vo

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Klotho protein expression has profound effects on lifespan where klotho-deficient mice exhibit premature aging phenotypes and live only to ~8 weeks of age while klotho-overexpressing mice have lifespans that are at least 20% longer than wild-type mice. Klotho expression also has similar effects on cognitive function as klotho-deficient mice develop cognitive impairment by 7 weeks of age and klotho-overexpressing mice show enhanced cognitive function. These effects also extend to humans as polymorphisms that alter circulating levels of klotho have likewise effects on lifespan and brain function. Despite the fact that modulation of klotho expression has reciprocal effects on cognitive function, …


Ventral Hippocampal Input To The Medial Prefrontal Cortex Regulates Social Memory, Mary Leann Phillips Jan 2019

Ventral Hippocampal Input To The Medial Prefrontal Cortex Regulates Social Memory, Mary Leann Phillips

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Both the ventral hippocampus (vHIP) and medial prefrontal cortex (mPFC) are active participants in the neural circuitry activated by social interaction, and are both necessary for certain aspects of social behavior. Additionally, synaptic projections from the ventral hippocampus (vHIP) to the medial prefrontal cortex (mPFC) are implicated in several neuropsychiatric disorders. Using the Mecp2 knockout (KO) mouse model of Rett syndrome, an autism-associated disorder with network level deficits in the vHIP and mPFC as well as aberrant social behavior, we strove to determine the role of vHIP-mPFC in social behavior. Here, we show that the vHIP-mPFC projection is hyperactive in …


The Electronic Health Record And The Clinical Informatics Researcher: A Journey To Predicting False Positive Alerts With Patient Characteristics, Timothy Kennell Jan 2019

The Electronic Health Record And The Clinical Informatics Researcher: A Journey To Predicting False Positive Alerts With Patient Characteristics, Timothy Kennell

All ETDs from UAB

Since their introduction in the 1960s, electronic medical systems have brought with them tremendous opportunities and difficult challenges. In order to address patient safety, Clinical Decision Support (CDS) was added to the system, many times in the form of "pop-up" alerts. However, traditional alert typically do not incorporate enough patient-specific context resulting in inaccurate warnings. In response, clinicians override many of them. However, the high exposure to false positive alerts results in alert fatigue, a desensitization to future ones. This issue decreases patient safety by causing clinicians to ignore legitimate alerts. Despite some shortcomings, the data in modern Electronic Health …


Genome Sequencing To Identify Novel Developmental Disorder Variation, Matthew Neu Jan 2019

Genome Sequencing To Identify Novel Developmental Disorder Variation, Matthew Neu

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The ability to quickly and accurately catalog an individual's genetic variation through genome sequencing has ignited a new era of diagnostic and therapeutic development for heritable disease. Although genome sequencing can provide a molecular diagnosis in a significant number of patients with suspected genetic disease, there remain a number of unsolved cases for which no pathogenic cause can be determined. This uncertainty can create a "diagnostic odyssey" in which sequential tests fail to provide a diagnostic resolution and can often delay beneficial treatment, impact family planning, and be emotionally challenging for patients and their families. Clearly, there is an unmet …


Bet Bromodomain Inhibition As An Approach For Treatment Of Cholangiocarcinoma, Samuel Charles Fehling Jan 2019

Bet Bromodomain Inhibition As An Approach For Treatment Of Cholangiocarcinoma, Samuel Charles Fehling

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Cholangiocarcinoma (CCA) is a highly aggressive neoplasm which arises from the epithelial layer of the biliary tract. It is the second most common primary hepatic malignancy. As CCA is typically diagnosed at late disease stage, the current standard of care, resection followed by gemcitabine with cisplatin, is not effective. Further, up to 90% of CCA patients are ineligible for resection. Of those eligible for resection, postoperative chemotherapy does not prolong overall survival leading to a 5-year survival of ~30%. Previously, mutations have been identified in KRAS (17% of CCA cases), TP53 (44%) and SMAD4 (17%) but none have been recognized …


Identification Of Two Spop-Mediated Pathways In Prostate Cancer Progression, Joshua Fried Jan 2019

Identification Of Two Spop-Mediated Pathways In Prostate Cancer Progression, Joshua Fried

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Prostate cancer is one of the most common malignancies and causes of cancer related death in men. Morbidity is primarily attributed to late-stage and metastatic disease. Re-cent genomic screening studies have revealed that the Speckle type Poz Protein (SPOP) is the most frequently altered gene by missense mutations in prostate cancer. Interestingly, all of the identified mutations were located in the substrate binding domain of SPOP. Here, two pathways highlighting the impact of SPOP mutation on prostate cancer are pre-sented. First, evidence showing that one of the naturally occurring SPOP mutations, ser-ine 119 to asparagine (S119N), induces radiosensitivity and an …


The Influence Of O-Glcnacylation On Dna 5-Hydroxymethylation In The Epileptic Hippocampus, Richard Gilbert Sanchez Jan 2019

The Influence Of O-Glcnacylation On Dna 5-Hydroxymethylation In The Epileptic Hippocampus, Richard Gilbert Sanchez

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Epilepsy is a neurological disorder that affects roughly 3 million Americans and 65 million individuals worldwide. Although there are several known causes of epilepsy, little is understood about the development of epilepsy or epileptogenesis. What has been observed through multiple studies of epilepsy is an alteration of the proteomic profile, along with a distinct change in post-translational modifications (PTM). Studies have focused on phosphorylation and a variety of kinases that are upregulated during epilepsy with little clinical translation. This dissertation investigates O-GlcNAcylation, a PTM that is highly intertwined with the cellular metabolism, and its epigenetic effects on gene expression via …


Targeting The Nad Salvage Pathway For The Treatment Of The Parasitic Disease Schistosomiasis, Michael David Schultz Jan 2019

Targeting The Nad Salvage Pathway For The Treatment Of The Parasitic Disease Schistosomiasis, Michael David Schultz

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Schistosomiasis, also known as bilharzia, is the third most common parasitic infection worldwide and a major source of morbidity and mortality in developing countries. Caused by trematodes in the genus Schistosoma, this parasitic disease has no vaccine therapy and resources for drug development are scarce. Despite an unknown mechanism of action, praziquantal has become the primary source of treatment due to its efficacy against all species of Schistosoma. However, with increased drug resistance in endemic areas and low activity against immature parasites, relying on this single drug is unsustainable and risky. Hence, there is a growing need for new, safe …


Novel Approaches To Enhance Translational Readthrough Efficacy For Cystic Fibrosis Nonsense Mutations, Jyoti Sharma Jan 2019

Novel Approaches To Enhance Translational Readthrough Efficacy For Cystic Fibrosis Nonsense Mutations, Jyoti Sharma

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Cystic fibrosis (CF) is a monogenic autosomal recessive disease caused by over 1,900 naturally occurring variants in the CF transmembrane conductance regulator (CFTR). CFTR is an epithelial anion channel which regulates the movement of chloride and bicarbonate ions. Mutations in the CFTR causes diminished CFTR protein and/or reduced CFTR function that lead to clinical manifestations. These include severe epithelial dysfunction of multiple tissues, including the lungs, intestine, pancreas, and reproductive organs. Premature termination codons (PTC), or nonsense mutations, are among the most severe CFTR variants and occur in ~11% of the CF population. PTCs are caused by the presence of …


Acetylcholine Signaling In Glioblastoma Invasion And Peritumoral Hyperexcitability, Emily Grace Thompson Jan 2019

Acetylcholine Signaling In Glioblastoma Invasion And Peritumoral Hyperexcitability, Emily Grace Thompson

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Glioblastomas are the most common and deadly form of primary brain cancer in adults. Current treatment strategies are aggressive, including a combination of surgical resection, radiotherapy, and chemotherapy. However, median patient survival has remained stagnant at 12 to 15 months for the last several decades. This dismal patient outcome has prompted efforts to understand the unique characteristics of these tumors, since traditional therapeutics have not been efficacious. Extensive invasion is a salient feature of glioblastomas that significantly diminishes the effectiveness of current treatment strategies and is ultimately the cause of tumor recurrence within 2 years in approximately 80% of patients. …


The Anti-Tumor Effects Of Hur Inhibition In Glioblastoma, Jiping Wang Jan 2019

The Anti-Tumor Effects Of Hur Inhibition In Glioblastoma, Jiping Wang

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Glioblastomas (GBMs) are the most malignant primary brain tumor. GBMs represent 14.7% of total primary CNS tumors and 47.7% of malignant CNS tumors. The median survival of GBM is 18-20 months, while five-year survival rate is only 5.6%. GBMs are maintained by glioma stem cells (GSCs), and poor treatment outcomes are linked to the high resistance of GSCs to radiation and chemotherapy, and the immunosuppressive tumor microenvironment. The mRNA binding protein HuR is a key regulator of tumor growth and development based upon the fact that HuR targets mRNAs that are broadly involved in tumorigenesis. We have previously shown that …


Bk Polyomavirus Activates The Dna Damage Response To Hijack Host Cell Cycle Control, Joshua L. Justice Jan 2019

Bk Polyomavirus Activates The Dna Damage Response To Hijack Host Cell Cycle Control, Joshua L. Justice

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BK Polyomavirus (BKPyV) is a DNA tumor virus that latently infects the >90% of humanity. BKPyV infection is inconsequential in healthy individuals; however, the immunocompromised carry increased risk of viral reactivation that can lead to a number of genitourinary diseases. Overall, BKPyV reactivation is a major risk factor for kidney dysfunction and failure following solid organ transplantation. There are no approved therapeutics to treat BKPyV infection, therefore studies have focused on understanding the host/virus interactions that drive infection to identify therapeutic targets. The PyV genome is small and does not encode a polymerase. Cellular transformation by the viral oncogene, T …


Structural And Functional Insights Into The Influenza A Virus Non-Structural Protein 1 Effector Domain, Alex Kleinpeter Jan 2019

Structural And Functional Insights Into The Influenza A Virus Non-Structural Protein 1 Effector Domain, Alex Kleinpeter

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The influenza A virus (IAV) non-structural protein 1 (NS1) is a highly multifunctional viral protein responsible for antagonizing the type-I interferon (IFN) response to infection. NS1 has therefore been identified as a potentially effective target for the development of novel anti-influenza compounds. Furthermore, it is important to understand the molecular underpinnings driving NS1 function to more effectively elucidate antiviral targets. In this dissertation, we have contributed significant insight into NS1’s potential as an antiviral target, and the structure-function relationships driving its activity in an infected cell. First, we structurally characterized the binding of two known influenza inhibitors (A9 and A22) …


O-Glcnac Regulation Of Inhibitory Circuits, Kavitha Abiraman Jan 2019

O-Glcnac Regulation Of Inhibitory Circuits, Kavitha Abiraman

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Post translational modification of proteins plays a crucial role in regulating their function, and the role of one such modification, termed O-GlcNAcylation, is understudied. O-GlcNAcylation involves the dynamic cycle of adding and removing an O-linked N-acetylglucosamine (O-GlcNAc) by the enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which are highly expressed in the hippocampus. Enzymes that catalyze O-GlcNAcylation are found at both presynaptic and postsynaptic sites, and O-GlcNAcylated proteins localize to synaptosomes. We have shown that acute and selective increase in O-GlcNAcylation of AMPAR GluA2 subunits underlies expression of a novel form of LTD at CA3-CA1 synapses (O-GlcNAc LTD), as well …


Investigating The Rho-Kinase (Rock) Signaling Pathway As A Therapeutic Target In Alzheimer’S Disease, Benjamin Wade Henderson Jan 2019

Investigating The Rho-Kinase (Rock) Signaling Pathway As A Therapeutic Target In Alzheimer’S Disease, Benjamin Wade Henderson

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Current estimates project that there are approximately 5.4 million Americans affected by Alzheimer’s disease (AD). While this number is expected to dramatically increase in the years to come, there is currently no disease modifying therapeutic to prevent or slow AD progression. Cognitive decline is a clinical hallmark of AD, while accumulation of amyloid-β (Aβ) is a pathological hallmark. Work in the field has demonstrated that mitigating Aβ levels may serve as a rational therapeutic avenue to slow progression of the disease. Pharmacologic inhibition of the Rho-associated protein kinases (ROCK1 and ROCK2) is proposed to curb Aβ levels, and mechanisms that …


Characterization Of The Tgfb Pathway And Its Role In Prostaglandin Metabolism In C. Elegans, Muhan Hu Jan 2019

Characterization Of The Tgfb Pathway And Its Role In Prostaglandin Metabolism In C. Elegans, Muhan Hu

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Cell to cell communication is fundamental to all life processes, from fertilization to death. The TGFߟ superfamily is a large family of proteins that is involved in a wide array of physiological and pathological processes, including development, wound healing, immune system function, cancer, and reproduction. This group of signaling peptides is well conserved across many organisms, from basic nematode to humans. While many studies have aimed to delineate the functions of TGFߟ, they have also unveiled the complexity of this multifunctional family of ligands. In this thesis, I take advantage of the simple C. elegans model system to study the …


Baf Chromatin Landscaping During Bone Formation And Maintenance, Tanner Cole Godfrey Jan 2019

Baf Chromatin Landscaping During Bone Formation And Maintenance, Tanner Cole Godfrey

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Bone loss is a worldwide problem resulting in increased risk of fracture. Osteoblasts are responsible for bone synthesis; therefore, treatments promoting osteoblast differentiation and/or activity would result in increased bone formation. The regulation of DNA accessibility is a key mechanism controlling gene expression and cellular differentiation. BAF (BRG1 Associated Factor) mediated chromatin remodeling increases DNA accessibility by sliding or ejecting nucleosomes. This process can occur in a cell type specific manner based on the composition of BAF. In many tissue types, a unique combination of BAF subunits has been identified to be responsible for the maintenance or differentiation of that …


The Role Of Nudc In Rod Photoreceptor Cell Maintenance: A New Function For An Old Protein, Evan Boitet Jan 2019

The Role Of Nudc In Rod Photoreceptor Cell Maintenance: A New Function For An Old Protein, Evan Boitet

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The overall health and maintenance of rod photoreceptors depends on directed vectorial transport of rhodopsin from its synthesis within the inner segment to its target destination the outer segment disk membranes. Numerous proteins are known to be involved in molecular interactions with rhodopsin during transport, including the interaction of nuclear distribution protein C (nudC) with rhodopsin that was first described in Xenopus laevis. We found that the interaction of nudC and rhodopsin is conserved in mammalian retina. This interaction is direct and aberrant expression of nudC results in subcellular localization of rhodopsin. We show for the first time that nudC …


Receptor Sialylation By St6gal-I Promotes Tumor Progression By Enhancing Tumor Cell Survival And Epithelial To Mesenchymal Transition, Colleen Maeve Britain Jan 2019

Receptor Sialylation By St6gal-I Promotes Tumor Progression By Enhancing Tumor Cell Survival And Epithelial To Mesenchymal Transition, Colleen Maeve Britain

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The upregulation of a certain subset of glycosyltransferases was an early marker for cancer development. Specifically, ST6Gal-I, which adds an α2-6 linked sialic acid to N-glycans on proteins bound for the plasma membrane or secretion, is selectively upregulated upon malignant transformation. Our laboratory has shown that ST6Gal-I is implicated in many facets of tumor biology and is an important mediator of tumorigenesis. For example, ST6Gal-I activity promotes the survival of cells when challenged with hypoxia, FasL, or TNFα, confers resistance to chemotherapeutics, enhances tumor cell migration and invasion, and fosters a cancer stem cell phenotype. The work presented in this …


Therapeutic Mechanisms In Sickle Cell Nephropathy, Crystal Taylor Jan 2019

Therapeutic Mechanisms In Sickle Cell Nephropathy, Crystal Taylor

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Sickle cell disease (SCD) is a commonly inherited genetic blood disorder that causes hypoxia-induced polymerization of mutant hemoglobin resulting in erythrocyte sickling, transient microvascular occlusion, ischemic injury, and end-organ damage. Systemic endothelial dysfunction and vaso-occlusive episodes observed in SCD are particularly deleterious to the kidney, where the hypoxic, hyperosmotic environment of the medulla makes it particularly susceptible to ischemic injury. Over recent decades, chronic kidney disease has emerged as a significant contributor to mortality and morbidity in SCD patients. Despite a growing interest in the importance of sickle cell nephropathy (SCN), therapeutic options are limited and much remains undiscovered regarding …


The Reductive Stress Reducto-Mir: Emerging Insight Into Microrna-671, Justin Michael Quiles Jan 2019

The Reductive Stress Reducto-Mir: Emerging Insight Into Microrna-671, Justin Michael Quiles

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Excessive accumulation of reactive oxygen and nitrogen species (ROS/RNS) promotes cardiac pathophysiology. Although extreme oxidative burden is cytotoxic, ROS/RNS are continually generated within multiple domains of cardiac myocytes, and these species play fundamental roles in signal transduction through reversible thiol oxidation. Nuclear factor, erythroid 2 Like 2 (Nfe2l2/NRF2) is activated by ROS/RNS and binds cis regulatory antioxidant response elements (AREs) to induce the expression of a host of thiol oxidoreductases which regulate signaling events at the post-translational, transcriptional and epigenetic levels. Although oxidative stress has been linked to cardiac disease, adaptive processes in the heart require reduction-oxidation (redox) reactions as …


Determination Of The Role Of Smu_833 In The Fitness And Virulence Of Cariogenic Streptococcus Mutans, Katherine Lynn Rainey Jan 2019

Determination Of The Role Of Smu_833 In The Fitness And Virulence Of Cariogenic Streptococcus Mutans, Katherine Lynn Rainey

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Dental caries, commonly known as tooth decay, is the most common infectious disease worldwide. The main etiological agent of dental caries is Streptococcus mutans which can readily form a biofilm on the surface of teeth and produce acids through the metabolism of dietary sugars, which is largely responsible for the demineralization and subsequent destruction of tooth enamel. In addition, S. mutans synthesizes extracellular glucosyltransferases (Gtfs) capable of breaking apart dietary sucrose and polymerizing the glucose subunits into the sticky glucan matrix of the biofilm, imperative for the formation of robust, three-dimensional biofilms. Currently used caries therapies are not species-specific and …