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Full-Text Articles in Medicine and Health Sciences
Ribosomal Rna Synthesis Is Regulated By Pathways That Respond To Environmental And Stress Conditions, Saman Najmi
Ribosomal Rna Synthesis Is Regulated By Pathways That Respond To Environmental And Stress Conditions, Saman Najmi
All ETDs from UAB
Ribosome biogenesis is one of the most central processes to cellular growth and metabolism. The synthesis of ribosomal RNA (rRNA) by RNA polymerase I (Pol I) is thought to be rate limiting for ribosome biogenesis, and is therefore subject to extensive regulation. The work presented in this dissertation characterizes two previously undiscovered pathways regulating rRNA synthesis. Due to the direct connection between ribosome biogenesis (and rRNA synthesis) and cellular proliferative potential, Pol I activity is upregulated in cancers. Cancer cells are hypersensitive to inhibition of Pol I, a quality that makes Pol I an attractive target for anticancer therapeutics. The …
Regulation Of Intestinal Innate Lymphoid Cells In Acute And Chronic Inflammation, Sarah Dulson
Regulation Of Intestinal Innate Lymphoid Cells In Acute And Chronic Inflammation, Sarah Dulson
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The Innate Lymphoid Cell (ILC) population encompasses five subpopulations that are increasingly appreciated to participate in immune responses to inflammation and injury as well as directly influence homeostasis in tissues throughout the body. ILCs are enriched at mucosal surfaces, such as the gastrointestinal tract, where they are transcriptionally poised for rapid activation. Therefore, ILCs contribute significantly to protective responses to infection, and can exacerbate inflammation and disease when dysregulated. Herein, we demonstrate two pathways that regulate intestinal ILC phenotype and function and delineate the impact of these pathways on both protective and pathogenic roles of ILCs. Using a murine model …
Intracellular Compartment-Specific Abnormalities In Proteasome Expression And Activity In The Superior Temporal Gyrus In Schizophrenia, Madeline R. Scott
Intracellular Compartment-Specific Abnormalities In Proteasome Expression And Activity In The Superior Temporal Gyrus In Schizophrenia, Madeline R. Scott
All ETDs from UAB
Protein homeostasis is an emerging component of schizophrenia (SZ) pathophysiology. Proteomic alterations in SZ are well-documented; however the underlying mechanism driving these changes remains unknown. The ubiquitin proteasome system (UPS) is fundamental to protein homeostasis regulation, and UPS transcript abnormalities in both blood and brain have been observed in SZ. Supporting a role for UPS dysfunction in SZ, we have reported decreased protein expression of ubiquitin-associated proteins in SZ brain. However, previous work on the proteasome has been limited to transcript expression. In the following studies we sought to address this gap in knowledge by characterizing proteasome dysfunction in the …
Bdnf/Trkb.T1 Signaling: A Novel Mechanism Of Astrocyte Morphological Maturation, Leanne Holt
Bdnf/Trkb.T1 Signaling: A Novel Mechanism Of Astrocyte Morphological Maturation, Leanne Holt
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Astrocytic morphogenesis and maturation are critical steps in central nervous system (CNS) development. During morphological maturation, astrocytes extend fine peripheral processes which infiltrate the neuropil and form intimate partners with neuronal structures, including synapses, where they facilitate neurotransmitter and K+ uptake and contribute to synaptic development and stabilization. The developmental time window of astrocyte morphological maturation and refinement is well defined, but the molecular mechanisms that underlie this process are not understood. Brain derived neurotrophic factor (BDNF) is a critical growth factor involved in the development and maturation of neurons. We developed a novel technique for the specific isolation of …
The Anti-Tumor Effects Of Hur Inhibition In Glioblastoma, Jiping Wang
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 …
Appropriately Timed Epigenetic Manipulation With Histone Deacetylase Inhibitors As A Platform Approach To Tumor Immunotherapy, Tyler Mccaw
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In contrast to chemotherapy and radiotherapy, immunotherapy is able to respond in proportion to tumor burden and continue to evolve in parallel with the tumor mass and metastatic sites. In this way, immune-based cancer therapies are a living drug and hold enormous potential. In this work, we enforce expression of MHCII on a murine breast cancer model to study how changes in tumor biology can drive improved T cell-mediated responses. We next use histone deacetylase inhibitors to manipulate the microenvironment through a more clinically relevant, therapeutic approach. Herein, improvements in tumor control were driven by CD8 T cells and IFNγ, …
Bk Polyomavirus Activates The Dna Damage Response To Hijack Host Cell Cycle Control, Joshua L. Justice
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 …
Integration Of Yeast Phenomics And Cancer Pharmacogenomics To Model Precision Medicine, Sean Santos
Integration Of Yeast Phenomics And Cancer Pharmacogenomics To Model Precision Medicine, Sean Santos
All ETDs from UAB
Precision medicine aims to optimize disease treatment by considering the differential influence of functional genetic variation on phenotypic outcomes and therapeutic efficacy. However, current precision medicine paradigms lack consideration of the abundance of genetic interaction and ensuing complexity of phenotypes, thus thwarting resolution of gene-drug interaction at a systems level and ‘precise’ predictions for most patients. Yeast phenomics enables quantitative, high-resolution experimental modeling of gene-drug interaction phenotypes at a systems level by measuring growth curves for the ~6000 yeast knockout/knockdown library strains, which can guide a more global resolution of disease and treatment complexity at the organism level. We postulate …
Targeting The Nad Salvage Pathway For The Treatment Of The Parasitic Disease Schistosomiasis, Michael David Schultz
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
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 …
Mechanisms Of Acute Kidney Injury: The Role Of Ferritin Heavy Chain In Renal Heme-Unology, Laurence Marie Black
Mechanisms Of Acute Kidney Injury: The Role Of Ferritin Heavy Chain In Renal Heme-Unology, Laurence Marie Black
All ETDs from UAB
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 …
Receptor Sialylation By St6gal-I Promotes Tumor Progression By Enhancing Tumor Cell Survival And Epithelial To Mesenchymal Transition, Colleen Maeve Britain
Receptor Sialylation By St6gal-I Promotes Tumor Progression By Enhancing Tumor Cell Survival And Epithelial To Mesenchymal Transition, Colleen Maeve Britain
All ETDs from UAB
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 …
Baf Chromatin Landscaping During Bone Formation And Maintenance, Tanner Cole Godfrey
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 …
Bet Bromodomain Inhibition As An Approach For Treatment Of Cholangiocarcinoma, Samuel Charles Fehling
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 …
Regulation Of St6gal-I In Cancer: Sox2 Identified As Novel Driver Of St6gal-I Expression, Kaitlyn Alexandra Dorsett
Regulation Of St6gal-I In Cancer: Sox2 Identified As Novel Driver Of St6gal-I Expression, Kaitlyn Alexandra Dorsett
All ETDs from UAB
ST6Gal-I is a sialyltransferase that functions to add an 2-6 linked sialic acid to N-linked glycoproteins. The expression of ST6Gal-I is upregulated in many cancers at both the mRNA and protein levels. ST6Gal-I has also been shown to promote cancer stem cell (CSC) characteristics including chemoresistance, tumor-initiating potential, and spheroid growth. However, the transcriptional drivers of ST6Gal-I expression in stem-like cells remain largely unknown. Herein we highlight that SOX2 and ST6GAL1 are both located on one of the most commonly amplified chromosomal segments in cancer, amplicon 3q26. Copy number gains in both SOX2 and ST6GAL1 are observed in roughly 25% …
Characterization Of The Tgfb Pathway And Its Role In Prostaglandin Metabolism In C. Elegans, Muhan Hu
Characterization Of The Tgfb Pathway And Its Role In Prostaglandin Metabolism In C. Elegans, Muhan Hu
All ETDs from UAB
Cell to cell communication is fundamental to all life processes, from fertilization to death. The TGFß 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 TGFß, 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 …
The Reductive Stress Reducto-Mir: Emerging Insight Into Microrna-671, Justin Michael Quiles
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 …
The Role Of Suppressor Of Cytokine Signaling 3 In Neuroinflammatory Disease, Zhaoqi Yan
The Role Of Suppressor Of Cytokine Signaling 3 In Neuroinflammatory Disease, Zhaoqi Yan
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The Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) pathway plays a critical role in cytokine-mediated responses in both innate and adaptive immunity, and dysregulation of the JAK/STAT pathway is linked to many inflammatory disorders. Multiple Sclerosis (MS) is an inflammatory demyelinating disease that affects the central nervous system, and both innate and adaptive immunity are involved in disease progression. STAT3 signaling is critically involved in MS pathology and is negatively regulated by Suppressor Of Cytokine Signaling 3 (SOCS3). Both increased STAT3 activation and reduced SOCS3 expression are observed in immune cells from patients with MS. Although the role of …
Structural And Functional Insights Into The Influenza A Virus Non-Structural Protein 1 Effector Domain, Alex Kleinpeter
Structural And Functional Insights Into The Influenza A Virus Non-Structural Protein 1 Effector Domain, Alex Kleinpeter
All ETDs from UAB
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) …
Early Life Stress And Immune Responses In Adult Rat Kidneys, Ijeoma E. Obi
Early Life Stress And Immune Responses In Adult Rat Kidneys, Ijeoma E. Obi
All ETDs from UAB
Globally, human studies show overwhelming associations between adverse childhood experiences and cardiovascular disease (CVD) and CVD risks throughout adult life. As early as 6 years old, there are significant associations between childhood adversity and inflammation, and those association are observed throughout adult life as well. Over a decade ago, rodent models were used to establish the importance of the immune cells in hypertension, which is the major risk factor in developing CVD. Although these associations in humans are important, they pose several limitations that can be overcome by the use of animal models to study the molecular mechanisms that are …
The Role Of Protein O-Glcnacylation In Regulating Mitochondrial Function, Jalessa Nicole Wright
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 …
Modulation Of Klotho Affects Dendritic Spine Remodeling And Neuronal Network Activity, Hai T. Vo
Modulation Of Klotho Affects Dendritic Spine Remodeling And Neuronal Network Activity, Hai T. Vo
All ETDs from UAB
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, …
Using Peptide Mimetics To Probe Protein-Protein Interactions Significant In Cancers, Robert H. Whitaker
Using Peptide Mimetics To Probe Protein-Protein Interactions Significant In Cancers, Robert H. Whitaker
All ETDs from UAB
Protein-protein interactions are critical for cell life. One aspect of cellular regulation where such protein-protein interactions occur is in the highly regulated process of programmed cell death (or apoptosis). Apoptosis is critical for normal tissue homeostasis, differentiation, and if dysregulated is a driver of disease including cancers. At the center of apoptotic regulation is the BCL2 protein family whose intra-familial protein-protein interactions balance cell stress signaling either allowing the cell to survive or inducing mitochondrial cell death. These BCL2 protein interactions are accomplished through the BH3 motif. While unique to the BCL2 family, a similar motif, the reverse BH3, has …
Endothelial N-Glycan Hypoglycosylation Enhances Cd16+ Monocyte Adhesion: A Role For Alpha-Mannosidases, Kellie Regal Mcdonald
Endothelial N-Glycan Hypoglycosylation Enhances Cd16+ Monocyte Adhesion: A Role For Alpha-Mannosidases, Kellie Regal Mcdonald
All ETDs from UAB
Monocyte extravasation through the endothelial layer is a hallmark of atherosclerotic plaque development and is mediated by heavily glycosylated surface adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1). Human monocytes have been classified into three distinct groups: classical (anti-inflammatory; CD14+/CD16-), nonclassical (patrolling; CD14+/CD16++), and intermediate (pro-inflammatory; CD14++/CD16+). The CD16+ nonclassical / intermediate monocytes have been implicated in atherosclerosis progression and their levels positively associate with adverse cardiac events. However, there is a relative lack of understanding as to whether there are distinct mechanisms that regulate CD16+ vs. CD16- monocyte adhesion to the inflamed endothelium. Our previous data identified a high-mannose …
Ventral Hippocampal Input To The Medial Prefrontal Cortex Regulates Social Memory, Mary Leann Phillips
Ventral Hippocampal Input To The Medial Prefrontal Cortex Regulates Social Memory, Mary Leann Phillips
All ETDs from UAB
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 …
Characterizing The Hiv-1 Envelope N-Glycan Shield, Audra Ann Hargett
Characterizing The Hiv-1 Envelope N-Glycan Shield, Audra Ann Hargett
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In 2017, there was an estimated 1.8 million new HIV-1 infections worldwide. Development of an effective HIV-1 vaccine would begin to quell this global pandemic. HIV-1 envelope (Env) glycoprotein is the main vaccine candidate target due to the immune systems ability to generate broadly neutralizing antibodies (bnAbs) against Env. Approximately 90 N-glycans form a glycan shield that is the primary interface between the virus and host immune system. Key glycan motifs within the glycan shield are targets for bnAbs and are necessary for HIV-1 infectivity. Herein, we explore how naturally occurring mutations alter the glycan shield and HIV-1 Env function. …
Pannexin 1 Channel Inhibition To Prevent Triggered Arrhythmia, Grace Elizabeth Salzer
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
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 …
Characterization Of Chemical Uptake And Aryl Hydrocarbon Receptor Mutations In Zebrafish, Jaclyn Paige Souder
Characterization Of Chemical Uptake And Aryl Hydrocarbon Receptor Mutations In Zebrafish, Jaclyn Paige Souder
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In a society driven by technology and industry, we must be increasingly aware of how changes to our environment impact our health. This is especially true concerning embryonic development, which is easily influenced by extra-embryonic factors, including environmental contaminants. Determining how exogenous compounds are absorbed, which receptors they act through, and how these receptors act endogenously is important to fully understand to what extent developmental exposures impact fetal and adult health. I have used the zebrafish model system to address these questions for two classes of environmentally-relevant chemicals—estrogens and dioxins. First, I developed an assay to measure the uptake of …
O-Glcnac Regulation Of Inhibitory Circuits, Kavitha Abiraman
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 …