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University of Alabama at Birmingham

Theses/Dissertations

2022

Doctor of Philosophy (PhD) Heersink School of Medicine

Articles 1 - 30 of 38

Full-Text Articles in Medicine and Health Sciences

Elucidating Pgc-1Α And Errγ Gene Regulation In Neurons, Kathlene Lanphear Joyce Jan 2022

Elucidating Pgc-1Α And Errγ Gene Regulation In Neurons, Kathlene Lanphear Joyce

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Neuronal energy production is critical to the function of the entire central nervous system. Without enough ATP, neurons are not able to maintain their synaptic structure or activity, leading to a circuit-wide dysregulation, affecting movement and memory. The main process for ATP production in neurons is oxidative phosphorylation, which is supported by several proteins encoded by nuclear DNA. Transcription of nuclear DNA is regulated by DNA-binding transcription factors and co-activators which recruit other members of the transcription initiation complex to induce gene expression. While important basally, during neurodegenerative diseases such as Parkinson’s Disease, the transcription of these genes is altered …


Primary Cilia Regulate Inflammation And Macrophage Accumulation During Injury And Cyst Formation In Mouse Pkd Models, Zhang Li Jan 2022

Primary Cilia Regulate Inflammation And Macrophage Accumulation During Injury And Cyst Formation In Mouse Pkd Models, Zhang Li

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Polycystic kidney disease (PKD) is one of the most common inherited renal disorders. The most common form, autosomal dominant polycystic kidney disease (ADPKD), affects more than 13 million people around the world, and over 50% of them will develop end-stage renal disease (ESRD). Although ADPKD genetically is caused by mutations of PKD1 or PKD2 genes, there is increasing evidence showing that non-genetic factors such as renal injury and inflammation play important roles in cyst severity and progression in PKD. Macrophages are cells of the innate immune system known to be involved in kidney injury and repair. Data from our lab …


Elucidating The Role Of Stat4 In Cd4 T Cell Mediated Pathogenicity, Ashlyn E. Anderson Jan 2022

Elucidating The Role Of Stat4 In Cd4 T Cell Mediated Pathogenicity, Ashlyn E. Anderson

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While the exact cause of many autoimmune diseases is currently unknown, many genetic factors are associated with increased disease susceptibility such as single nucleotide polymorphisms in the STAT4 gene locus. Signal Transducer and Activator of Transcription 4 (STAT4) is critical for the development and function of Th1 cells; however, many Th1 associated molecules are dispensable for CD4 mediated inflammation such as IFNγ, T-bet, and IL-12Rβ2, suggesting that STAT4 may function outside of the Th1 cell lineage. Importantly, Stat4 has recently been correlated with an inflammatory Th17 cell phenotype. Using a murine model of neuroinflammation, we illustrate that Th17 intrinsic STAT4 …


Characterization Of The Phenotype And Functional Properties Of Myeloid Subpopulations In Chronic Inflammatory Conditions, Krystla Leandra Ong Jan 2022

Characterization Of The Phenotype And Functional Properties Of Myeloid Subpopulations In Chronic Inflammatory Conditions, Krystla Leandra Ong

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Myeloid cells represent a subset of leukocytes traditionally recognized as first responders to acute inflammatory stimuli. In recent years, there has been a growing appreciation of the role of myeloid cells as critical regulators of the immune system in disease pathogenesis and progression. Chronic inflammatory diseases including viral infections, autoimmune diseases, and malignancies are frequently associated with altered myelopoiesis characterized by a profound shift in the myeloid cell phenotype and function. The work presented in this dissertation provides an insight into dysregulated myelopoiesis and myeloid heterogeneity in multiple myeloma (MM), human immunodeficiency virus-1 (HIV-1), and coronavirus disease-19 (COVID-19). We identify …


The Role Of Dock3 In Normal Skeletal Muscle Function And Metabolism, Adrienne Samani Jan 2022

The Role Of Dock3 In Normal Skeletal Muscle Function And Metabolism, Adrienne Samani

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DOCK (dedicator of cytokinesis) are proteins of an 11-member family of typical guanine exchange factors (GEFs) expressed almost exclusively in the brain and spinal cord. Human pathogenic DOCK3 variants have been identified to cause debilitating neuromuscular phenotypes such as muscle hypotonia, ataxia, and intellectual disability. Our lab identified DOCK3 as being strongly upregulated in Duchene muscular dystrophy (DMD), specifically in the skeletal muscles of DMD patient and mouse skeletal muscles. Global Dock3 KO mice on the dystrophin-deficient background exacerbated skeletal muscle and cardiac phenotypes. Similarly, DOCK3 KO mice appeared to have poor muscle architecture, locomotive activity, reduced myogenic fusion, impaired …


Molecular Imaging Of Cancer For Detection And Monitoring Of Response To Combination Therapy, Tiara S. Napier Jan 2022

Molecular Imaging Of Cancer For Detection And Monitoring Of Response To Combination Therapy, Tiara S. Napier

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Imaging is a primary component of cancer care and aids in diagnosing, response assessment, and monitoring. Molecular imaging techniques provide visualization of unique tumor biology that can be used to personalize treatment. Key features of an effective biomarker are sensitivity, specificity, and ability to provide clinical value beyond that of other types of information already available at the time of diagnosis. For particularly heterogeneous cancer subtypes, such as glioblastoma (GBM) and triple negative breast cancer (TNBC), reliable biomarkers can be challenging to identify and there are few tar-getable receptors for therapy. Our findings demonstrate that quantifying tumor EGFR (panitumumab-IRDye800CW), granzyme …


Cell Type-Specific Diurnal Variation In Hippocampus Physiology, Lacy Kathryn Goode Jan 2022

Cell Type-Specific Diurnal Variation In Hippocampus Physiology, Lacy Kathryn Goode

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Circadian rhythms are biological processes that cycle across 24 hours. Driven endogenously by widely expressed and highly conserved clock genes that compose the circadian molecular clock, circadian rhythms are exhibited in numerous facets of physiology across nearly every tissue throughout the body. Diurnal rhythms in cognition, long-term potentiation (LTP), and the expression of clock genes in hippocampus subfields support a role for circadian regulation of hippocampus physiology. However, little is known regarding the circadian molecular clock and diurnal rhythms in neurophysiology at the cellular level. Here, we characterized diurnal differences in spatial memory, LTP, excitability of and synaptic transmission onto …


Three Heads Are Better Than One: A Structural Look At Staphylococcal Bacteriophage Capsids, N'Toia Chivon Hawkins Jan 2022

Three Heads Are Better Than One: A Structural Look At Staphylococcal Bacteriophage Capsids, N'Toia Chivon Hawkins

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Staphylococcal species such as S. aureus and S. epidermidis are opportunistic pathogens that are the leading causes of nosocomial infections. They have become of growing concern due to the virulence factors that they have acquired as well as their inability to be treated due to resistance to antibiotics. Bacteriophages have increasingly become a popular contender for eliminating these pathogens, however not every phage is suitable for the job. Size of the genome, life cycle, the ability to mobilize genomic material, and host range all factor into how well-suited a phage is to be used as a therapeutic. In this dissertation …


Defining Genetic Underpinnings Of Cellular Diversity And Vulnerability In The Context Of Parkinson's Disease, Stephanie M. Boas Jan 2022

Defining Genetic Underpinnings Of Cellular Diversity And Vulnerability In The Context Of Parkinson's Disease, Stephanie M. Boas

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Parkinson’s disease (PD) is a severe, progressive neurodegenerative movement disorder. Currently, there is no cure, nor effective treatments for prevention or modification of disease progression. Thus, novel approaches are required to understand etiological contributors to cell dysfunction and death in PD to enable rational drug design. Recently, huge advancements have been made in the technology involved in collection, storage, and processing of high-volume genetic information. Genome-wide association studies (GWAS) have been integral in identifying genomic loci with common, disease risk-associated variation. However, annotation and prioritization of GWAS-identified risk variants is far from straightforward, and the gap between the identification of …


Distinct Clinical Manifestations Associated With Autoantibodies And Cytokines In Systemic Lupus Erythematosus, Fatima K. Alduraibi Jan 2022

Distinct Clinical Manifestations Associated With Autoantibodies And Cytokines In Systemic Lupus Erythematosus, Fatima K. Alduraibi

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Objective: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by production of autoantibodies (autoAbs) and cytokines. Moreover, lupus nephritis (LN) occurs in approximately 50% of SLE patients. AutoAb and cytokine levels produced by B and T cells are high in LN patients, although their relationship with histological patterns requires investigation. Methods: We analyzed the relationship between B cell cytokines and major T cell cyto-kines, including their association with autoAbs, and the clinical manifestations of SLE, especially LN. We also analyzed endogenous intracellular interferon beta (IFNβ) expression in the peripheral blood mononuclear cells and serum circulating nephritogenic autoAbs from …


Nox2-Derived Superoxide And Mda5-Dependant Responses Contribute To Autoimmune Diabetes, Samuel Isaac Blum Jan 2022

Nox2-Derived Superoxide And Mda5-Dependant Responses Contribute To Autoimmune Diabetes, Samuel Isaac Blum

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NADPH oxidase 2 (NOX2)-derived superoxide, a precursor for many reactive oxygen species (ROS), regulates cell signaling, cellular trafficking, melanoma differentiation-associated protein 5 (MDA5) responses, and Type 1 diabetes (T1D). Previously, we demonstrated that NOX2-derived superoxide promotes chemokine synthesis, spontaneous and virus-accelerated T1D, and MDA5 responses to coxsackievirus B3 (CVB3), an associated environmental trigger for T1D. Yet, it remains unknown if ROS is necessary for diabetogenic T cell trafficking into islets or how MDA5 responses affect T1D. First, using non-obese diabetic (NOD) mice that contain an in-frame deletion within the helicase 1 domain of MDA5 (ΔHel1) or lack MDA5 expression (KO), …


Analysing The Structural Dynamics Of Retinoid X Receptor Using Hydrogen Deuterium Exchange Mass Spectrometry, Nathalia Melo Jan 2022

Analysing The Structural Dynamics Of Retinoid X Receptor Using Hydrogen Deuterium Exchange Mass Spectrometry, Nathalia Melo

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Nuclear receptors (NR) are ligand-activated transcription factors that are targets for drug discovery due to their ability to directly modulate gene expression. There are 48 NRs and approximately half of them require heterodimerization with retinoid X receptor (RXR) to function. Targretin (bexarotene) is an FDA-approved RXR specific (rexinoid) currently used to treat Cutaneous T-cell Lymphoma (CTCL); however, it causes hyperlipidemia toxicities. A functionally similar rexinoid developed at UAB, 9-cis-UAB30 (UAB30), is non-toxic and weak agonist in the liver. While UAB30 shows promise as a low toxicity chemopreventative drug, the mechanism of UAB30 action at the molecular level is poorly understood. …


Targeting The Frataxin Transcriptional Defect As A Therapeutic Approach For Friedreich's Ataxia, Anna Maria Schreiber Jan 2022

Targeting The Frataxin Transcriptional Defect As A Therapeutic Approach For Friedreich's Ataxia, Anna Maria Schreiber

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Friedreich’s ataxia (FRDA) is the most common inherited ataxia worldwide. This autosomal recessive neurodegenerative disorder manifests in the central and peripheral nervous system but also affects the cardiovascular and endocrine systems. No effective treatment is available. FRDA is caused by expansion of GAA repeat tracts in intron 1 of the frataxin (FXN) gene on both alleles. An inverse correlation between FXN levels and GAA repeat length exists. Frataxin is a mitochondrial protein participating in iron-sulfur (Fe-S) cluster formation. Frataxin deficiency results in reduced activity of Fe-S-containing enzymes involved in critical biological processes, such as cellular respiration and DNA repair. Expansion …


Applying Pet Imaging To Cancer Immunotherapy To Improve Clinical Outcomes, Kirsten M. Reeves Jan 2022

Applying Pet Imaging To Cancer Immunotherapy To Improve Clinical Outcomes, Kirsten M. Reeves

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The use of biomarkers has significantly enhanced patient outcome by improving diagnosis, personalizing therapy, and monitoring therapeutic response yet most cancers remain non-responsive. Thus, there is a need to better understand the underlying biological mechanisms and tumor microenvironment to enhance therapeutic efficacy. Molecular imaging, including magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) are used to assess response during oncology therapy. Molecular imaging can also provide a noninvasive approach to accurately quantify biomarkers correlated with the tumor microenvironment, including glucose metabolism and hypoxia. 18F-Fluoromisonidazole (18F-FMISO) hypoxia targeted cellular uptake has been shown to correlate with negative …


The Identification And Phenotypic Characterization Of Circulating Flagellin Antigen-Specific Cd4+ T Cells In Crohn's Disease Patients, Nadine N. Morgan Jan 2022

The Identification And Phenotypic Characterization Of Circulating Flagellin Antigen-Specific Cd4+ T Cells In Crohn's Disease Patients, Nadine N. Morgan

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The incidence of inflammatory bowel diseases (IBD) is increasing worldwide. Crohn’s disease (CD) and Ulcerative colitis (UC), the two main subtypes of IBD, are chronic intestinal conditions driven by CD4+ T-cell inflammatory responses to commensal antigen. Both conditions are incurable, and medical treatments involve drugs that require long-term usage but have limited efficacy and significant side effects. To develop therapies targeting the antigen-reactive T cells involved in sustaining these conditions, we must first gain knowledge concerning the microbial antigen-reactive T cell phenotypes and functionality in health and disease. To investigate the phenotypic and functional characteristics of the flagellin-reactive T cell …


Regulation Of Stromal Cells Through Inflammatory Signalling, Victoria Matkins Jan 2022

Regulation Of Stromal Cells Through Inflammatory Signalling, Victoria Matkins

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The bone marrow is a complex organization of hematopoietic and nonhematopoietic cells that form niches to maintain systemic homeostasis during stress and disease. Stromal cells are non-hematopoietic cells first proposed in 1978 in the bone marrow to be essential for hematopoietic stem cells (HSC). Since then, mesenchymal stromal cells (MSC) have been shown to be critical for the HSC self-renewal, retention, and differentiation through chemokines, cytokines, and adhesion molecules. However, like HSCs, MSCs are multipotent progenitors that differentiate into osteoblasts, adipocytes, and chondrocytes to from tissues of the skeletal, endocrine, and connective systems. These multipotent progenitors are tightly regulated in …


Determining The Impact Of Immune Dysregulation On Cd4 T Cell Responses To Hiv-1 And Sars-Cov-2, Jacob K. Files Jan 2022

Determining The Impact Of Immune Dysregulation On Cd4 T Cell Responses To Hiv-1 And Sars-Cov-2, Jacob K. Files

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CD4+ T cells, often referred to as helper T cells, play a crucial role in the formation of antiviral immune responses following infection and vaccination. However, this can be disrupted by various forms of immune dysregulation. Many groups have described how HIV-1 adaptation and immune escape can lead to dysregulated HIV-specific immune responses. Our lab has previously shown that predicted HLA-II associated HIV-1 adaptation leads to dysregulated, poorly immunogenic CD4+ T cell responses in HIV-1 infection. Here, we focus on the impact of this HLA-II associated viral adaptation in the setting of HIV-1 vaccination. We show that HLA-II associated, vaccine-matched …


Characterizing The Role Of Tissue-Specific Retinol Dehydrogenases, Kelli Rae Goggans Jan 2022

Characterizing The Role Of Tissue-Specific Retinol Dehydrogenases, Kelli Rae Goggans

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The bioactive form of vitamin A, retinoic acid is essential for development, cellular differentiation, epigenetic modifications, the immune system, and a variety of other processes due to its ability to regulate over 500 genes through activation of nuclear receptors. While many studies have focused on characterizing the biosynthesis and signaling of retinoic acid in embryogenesis, few have focused on adult tissues. Recent research has identified a novel retinol dehydrogenase, retinol dehydrogenase epidermal 2 (RDHE2), and shown RDHE2 is a potent, physiologically relevant retinol dehydrogenase in Xenopus. The work in this dissertation characterizes RDHE2 in mammalian models. We identify a paralog …


Il-2-Mediated Stat3 Activation Controls Effector T Regulatory Cell Development, Emma C. Dean Jan 2022

Il-2-Mediated Stat3 Activation Controls Effector T Regulatory Cell Development, Emma C. Dean

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Heterogeneity in phenotype and function of Treg cells is becoming increasingly appreciated, especially in the context of creating potent Treg cell–based therapeutics in the treatment of inflammatory bowel disease. One of the barriers to developing such therapeutics is the limited understanding of the signals that play a role in the development of Treg cell subsets. Here, we found STAT3 signaling to be enriched in induced IL-10 competent Treg (iTreg) cells in the colon. Through the development of a new in vitro system, we found that STAT3 was required for proper development of IL-10 competent iTreg cells and that IL-2 regulated …


Integrated Phenotypic And Molecular Expression Circuits In End-Stage Osteoarthritis, Devin J. Drummer Jan 2022

Integrated Phenotypic And Molecular Expression Circuits In End-Stage Osteoarthritis, Devin J. Drummer

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Osteoarthritis (OA) is a debilitating, inflammatory, joint degeneration disorder, and is the most common form of arthritis. Individuals reaching end-stage OA often pursue elective total hip/knee arthroplasty (THA/TKA) to relieve pain and improve mobility and quality of life. However, approximately one third of THA/TKA patients suffer long-term mobility impairments following surgery, likely in part due to an inability to repair the damaged muscle surrounding the diseased joint. Mechanisms driving this impaired recovery remain poorly understood, therefore it is prudent to interrogate the molecular signatures in skeletal muscle at the time of surgery to provide candidate markers that may improve upon …


The Role Of Mitochondrial Genetic Background In Cellular Function, Response To Cell Stress And Disease Susceptability, Jamelle A. Brown Jan 2022

The Role Of Mitochondrial Genetic Background In Cellular Function, Response To Cell Stress And Disease Susceptability, Jamelle A. Brown

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There is a differential susceptibility associated with several diseases including cardiovascular disease (CVD) and hypertension, with Blacks being more likely to develop these conditions. Blacks are also more likely to die from these diseases. To explain the genetic etiology underlying CVD pathogenesis, the primary focus has been on nuclear genetics-environmental interactions, whereas the contribution of mitochondrial genetics is less explored. Therefore, we sought to determine whether differences exist in cellular function and response to cell stress in healthy and diseased individuals with distinct mitochondrial genetic backgrounds. To determine this, we sought first to develop a technique to detect and quantify …


Molecular And Cellular Mechanisms Of Resistance Training-Induced Skeletal Muscle Hypertrophic Response Heterogeneity In Older Adults, Margaret Bell Jan 2022

Molecular And Cellular Mechanisms Of Resistance Training-Induced Skeletal Muscle Hypertrophic Response Heterogeneity In Older Adults, Margaret Bell

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Sarcopenia is a decrease in skeletal muscle (SKM) mass occurring with age. This disease is natural, so it is important to increase SKM mass to counteract. This need is seen in diseases leading to muscle atrophy (i.e., insulin resistance and diabetes). The most efficient way to promote SKM hypertrophy is resistance exercise training (RT), however there is high response heterogeneity. To investigate SKM heterogeneity and maximizing SKM hypertrophy, we conducted a double-blind two-site placebo controlled clinical trial: “Metformin to Augment Strength Training Effective Response in Seniors (MASTERS)”. Here participants > 65 years underwent RT for 14 weeks. Measurements of SKM mass …


Comprehensive Characterization Of Structural Variations Using Long-Read Sequencing Data, Yu Chen Jan 2022

Comprehensive Characterization Of Structural Variations Using Long-Read Sequencing Data, Yu Chen

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Structural variants (SVs) contribute to genomic diversity and play pathogenic roles in a wide range of genetic disorders. Accurate characterization of SVs is critical for genomic research and studies of disease mechanisms. The rapid development of Third-Generation Sequencing (TGS) technologies has largely increased sequencing read length compared to Next-Generation Sequencing (NGS), bringing both great potentials and challenges in SV discovery through alignment-based and assembly-based approaches. In order to take full advantage of TGS data, I have developed a suite of bioinformatics tools focusing on comprehensive characterization of SVs. For the alignment-based SV discovery, I have developed DeBreak to identify SVs …


The Role Of The Bone Marrow Microenvironment In Flt3-Itd Acute Myeloid Leukemia Stem Cell Resistance To Flt3 Inhibition, Nicholas R. Anderson Jan 2022

The Role Of The Bone Marrow Microenvironment In Flt3-Itd Acute Myeloid Leukemia Stem Cell Resistance To Flt3 Inhibition, Nicholas R. Anderson

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Acute myeloid leukemia (AML) is an aggressive, complex hematological malignancy. AML cases with constitutively-activating internal tandem duplications in the Flt3 receptor (Flt3-ITD) represent a distinct subtype of disease with poor prognosis, but unique opportunities for targeted therapy. Flt3-specific tyrosine kinase inhibitors (TKI) have entered clinical practice due to their ability to induce remissions in a large proportion of Flt3-mutant AML patients, but their long-term efficacy remains limited due to the persistence of leukemia stem cells (LSC) in the bone marrow (BM). Herein, we outline the importance of the bone marrow microenvironment (BMM) in harboring LSC through AML development and drug …


Molecular Mechanism And Impact Of Sox2 Regulation By The Transforming Growth Factor-Ss Members In Ovarian Cancer Survival And Metastasis, Zainab Shonibare Jan 2022

Molecular Mechanism And Impact Of Sox2 Regulation By The Transforming Growth Factor-Ss Members In Ovarian Cancer Survival And Metastasis, Zainab Shonibare

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Ovarian cancer is the second most common and deadliest cancer of the female reproductive system affecting women in the United States and worldwide. The poor survival outcome seen in ovarian cancer is attributed to the subtleness of its early-stage symptoms, resulting in a majority of patients at initial diagnosis presenting with an advanced-stage disease with metastasis to other parts of the body. Hence, there is an urgent need to better understand the molecular etiology of metastasis to help develop effective therapeutic options and improve clinical outcomes in ovarian cancer patients. Ovarian cancer, an intra-abdominal cancer, most preferably undergoes metastasis via …


Transcriptional Regulation Of Metabolism And Synaptic Function In Neurons, Stephanie N. Fox Jan 2022

Transcriptional Regulation Of Metabolism And Synaptic Function In Neurons, Stephanie N. Fox

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Mitochondrial dysfunction, transcriptional dysregulation, and protein aggregation are all unifying features of neurodegenerative disorders, including Parkinson’s Disease. Parkinson’s Disease is a debilitating movement disorder with no known cure, leading sci-entists to explore the underlying etiological contributors to neuronal dysfunction and loss to devise strategies for neuroprotection. Estrogen-related receptor gamma (ERRγ) is a member of a family of transcription factors which regulate the expression of mitochondrial genes. To determine whether ERRγ modulation can provide insight into transcriptional and mitochondrial dysfunction with neurodegeneration, the experiments in this thesis project determined 1) the importance of transcription of mitochondrial genes in disease as regu-lated …


Alterations In Synaptic Structure And Tau Phosphorylation In Alheimer's Disease, Courtney K. Walker Jan 2022

Alterations In Synaptic Structure And Tau Phosphorylation In Alheimer's Disease, Courtney K. Walker

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Alzheimer’s disease (AD) is the most common cause of dementia in individuals over the age of 65. Of the two hallmark pathologies of AD, tau neurofibrillary tangles (NFTs) correlate more strongly with cognitive decline than do Aβ plaques. NFTs form in the entorhinal cortex (EC) and appear in anatomically connected regions over time as disease progresses. This tau spreading may occur via synaptic connections. Most excitatory synapses occur on dendritic spines, which house the postsynaptic machinery. Spines are actin-rich, plastic structures that change their size and shape in response to synaptic activity in a process that is dependent on actin …


Synergy Between Stenotrophomonas Maltophilia And Pseudomonas Aeruginosa During Polymicrobial Airway Infections, Melissa Skye Mcdaniel Jan 2022

Synergy Between Stenotrophomonas Maltophilia And Pseudomonas Aeruginosa During Polymicrobial Airway Infections, Melissa Skye Mcdaniel

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Stenotrophomonas maltophilia is a Gram-negative bacillus that can act as an opportunistic pathogen in patients with respiratory diseases, including cystic fibrosis (CF) and ventilator-associated pneumonia. Infection with S. maltophilia is associated with worse lung function, but it remains unclear if this organism contributes directly to lung function decline. Lung infections are often polymicrobial, and S. maltophilia can be isolated from the lung with the key pulmonary pathogen Pseudomonas aeruginosa. In the first half of this work, we investigated the pathogenicity of S. maltophilia alone and during polymicrobial infection with P. aeruginosa. We used respiratory infections in mice to assess persistence …


Epigenetic Regulation Of Gene Expression In Temporal Lobe Epilepsy, Rebecca Mary Hauser Jan 2022

Epigenetic Regulation Of Gene Expression In Temporal Lobe Epilepsy, Rebecca Mary Hauser

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Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy and is characterized by seizures originating from the temporal lobe of the brain. A frequent seizure focus in TLE is the hippocampus, a structure located within the temporal lobe crucial for its role in memory formation. Seizures are an excess of synchronous excitation in the brain caused by a surplus of excitatory neurotransmission and a lack of sufficient inhibitory transmission. Coordinating the process of neuronal transmission is differential expression of genes likely resulting in an increase or decrease in proteins responsible for neural signaling such as neurotransmitters, ion …


The Requirement Of Transcriptional Lim Complex Co-Regulators For Pancreatic Endocrine Cell Development And Function, Eliana Davi Toren Jan 2022

The Requirement Of Transcriptional Lim Complex Co-Regulators For Pancreatic Endocrine Cell Development And Function, Eliana Davi Toren

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The prevalence and tremendous impact of diabetes mellitus has made glucose regulation of the insulin-producing -cell and surrounding pancreatic islet of Langerhans a center of public and research interests alike. A comprehensive understanding of these hormone-producing cells begins with their developmental origins. What are the genetic cues and participants in the tightly orchestrated process of their formation? Investigating the earliest determinants of islet-cell fate not only allows us to deeply understand mature - and islet-cell function, but also produces a data-driven template for how these cells can be reproduced in future stem-cell based diabetes therapies. LIM transcriptional complexes are indispensable …