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Full-Text Articles in Medical Sciences
Characterizing The Role Of Mapk Phosphatases In Age-Dependent Macrophage Dysfucntion And Increased Suceptiblity To Pneumonia In A Tnf-Dependent Manner, Katherine Lauren Kruckow
Characterizing The Role Of Mapk Phosphatases In Age-Dependent Macrophage Dysfucntion And Increased Suceptiblity To Pneumonia In A Tnf-Dependent Manner, Katherine Lauren Kruckow
All ETDs from UAB
Lower respiratory infections are the primary cause of infectious death among the elderly. One reason for this is ‘inflamm-aging,’ a chronic low-grade inflammatory state that develops with advanced age. Pertinently, our group has shown increases in TNF levels to be responsible for age-dependent macrophage dysfunction (ADMD) and, in turn, enhanced susceptibility to Streptococcus pneumoniae, the leading cause of community-acquired pneumonia. The underlying molecular mechanisms responsible, however, remain unclear. Following adoptive transfer of alveolar macrophages (AM) from aged (18+ months) or young (3-6 month) mice into young mice, followed by infection with S. pneumoniae, we found that aged AM were sufficient …
Time-Restricted Feeding Attenuates Obesity-Induced Muscle Dysfunction Through Energy Metabolism And Microbiota Modulation, Christopher Livelo
Time-Restricted Feeding Attenuates Obesity-Induced Muscle Dysfunction Through Energy Metabolism And Microbiota Modulation, Christopher Livelo
All ETDs from UAB
Obesity is a global epidemic that affects countless numbers of people caused by genetic and environmental factors including circadian disruption, which poses significant health risks to skeletal muscle physiology and other tissues. While a feeding fasting intervention known as time-restricted feeding (TRF) has been shown to mitigate obesity-related muscle dysfunction, the underlying mechanisms remain a subject of investigation. In this study, we delve into potential mechanisms underlying TRF's protective effects on muscle physiology in the context of diet- and genetic-induced obesity using Drosophila models. Our findings reveal that TRF triggers the upregulation of key genes involved in glycine production (Sardh …
Time-Restricted Feeding Modulates Dgat2 Expression In Cardiac And Skeletal Muscle, Yiming Guo Livelo
Time-Restricted Feeding Modulates Dgat2 Expression In Cardiac And Skeletal Muscle, Yiming Guo Livelo
All ETDs from UAB
Circadian disruption caused by aging, genetic, environmental, and lifestyle factors can lead to compromised cardiac and skeletal muscle function and potentially accelerate the progression of metabolic diseases. Time-restricted feeding/eating (TRF/TRE, referred to as TRF hereafter), a dietary intervention that confines food intake within a consistent window of the day, has pleiotropic benefits from flies and mice to humans. However, the effectiveness of TRF on heart and muscle in the context of various metabolic challenges such as circadian disruption and obesity is largely unknown. Current insights into the mechanisms of TRF are primarily based on multi-omics approaches, particularly transcriptomes; however, limited …
Molecular Imaging To Evaluate Tumor Heterogeneity And Guide Treatment Of Breast Cancer, Yun Lu
Molecular Imaging To Evaluate Tumor Heterogeneity And Guide Treatment Of Breast Cancer, Yun Lu
All ETDs from UAB
Molecular imaging plays an important role in predicting and evaluating treatment response and revealing the underlying biological mechanisms in the cancer field. Especially, PET imaging serves as a valuable tool for comprehending the tumor microenvironment (TME), allowing us to track tumor metabolism, proliferation, receptor expression, and immune infiltration. In this comprehensive study, three distinct aspects of cancer research were explored using molecular imaging techniques.The first study aimed to evaluate the accuracy of the fluorescence ubiquitination cell cycle indicator (FUCCI) system with fluorescence in vivo imaging compared to 3'-Deoxy-3'-[18F]fluorothymidine ([18F]-FLT) positron emission tomography (PET)/computed tomography (CT) in assessing cancer cell proliferation. …
Cd151+ T Cell Frequencies As An Immunological Clock That Identifies Premature Immunological Aging In People With Hiv, Mildred Perez
Cd151+ T Cell Frequencies As An Immunological Clock That Identifies Premature Immunological Aging In People With Hiv, Mildred Perez
All ETDs from UAB
Antiretroviral therapy (ART) has greatly improved the life expectancy of People With HIV (PWH), but despite ART, PWH show signs of chronic immune hyperactivation (CIH), which results in the development of early-onset comorbidities, such as metabolic syndrome, diabetes, cardiovascular complications, neurodegenerative impairment, and can-cer. The underlying causes of CIH are, at best, incompletely understood, with suggested roles of microbial translocation, viral coinfections, T cell imbalances, and persistent HIV replication. Given that the CD4+ T cell population is most affected during acute HIV infec-tion, it is surprising that no T cell populations have been identified as drivers of CIH. Herein, we …
Exercise-Driven Epigenetic And Transcriptomic Changes In An Experimental Model Of Temporal Lobe Epilepsy, Silvienne C. Sint Jago
Exercise-Driven Epigenetic And Transcriptomic Changes In An Experimental Model Of Temporal Lobe Epilepsy, Silvienne C. Sint Jago
All ETDs from UAB
Temporal lobe epilepsy (TLE) is a neurological disease marked by recurring unprovoked seizures originating from temporal lobe structures and is frequently associated with cognitive deficits. Exercise holds promise as a therapeutic approach to alleviate seizures and cognitive impairments in TLE. However, the exact cellular and molecular mechanisms by which exercise influences pathways related to seizure activity and cognition in the context of TLE still need to be understood. Neuronal network formation relies on the regulation of gene expression, which can lead to either an increase or a decrease in the production of essential proteins involved in neuronal signaling. Genes are …
The Influence Of Proximity On Patient Outcomes For Differently Structured Ambulatory Surgery Centers, Wendy Michelle Smith
The Influence Of Proximity On Patient Outcomes For Differently Structured Ambulatory Surgery Centers, Wendy Michelle Smith
All ETDs from UAB
THE INFLUENCE OF PROXIMITY ON PATIENT OUTCOMES FOR DIFFERENTLY STRUCTURED AMBULATORY SURGERY CENTERSWENDY SMITH HEALTH SERVICES ADMINISTRATION ABSTRACT This study examines the complication rates and patient-reported outcome measures (PROMs) for total hip and knee replacement surgeries conducted in one of two differently structured ambulatory surgical centers (ASCs) with varying interprofessional surgical teams. There is an ongoing shift from in-hospital total joint replacement surgeries to ASCs. Additionally, there is specialization occurring within ASCs. In this study, we compare single specialty ASCs designed to perform solely TJR surgeries with one orthopedic group and interprofessional team, with multi-specialty ASCs that perform an array …
Select Lipid Signaling. Derived From T-Cells Is An Important Contributor To Type 1 Diabetes Development, Tayleur White
Select Lipid Signaling. Derived From T-Cells Is An Important Contributor To Type 1 Diabetes Development, Tayleur White
All ETDs from UAB
We reported that Ca2+-independent phospholipase A2β (iPLA2) contributes to type 1 diabetes (T1D) development; however, the impact of lipid signaling from T-cells is unknown. To address this, we first administered splenocytes from NOD, NOD.iPLA2+/- (NOD.HET), or NOD.iPLA2-/- (NOD.KO) mice to 4-week-old NOD.scid recipients. As expected, T1D onset was rapid in NOD cell recipients and 100% by 12 weeks. However, onset was delayed by 1-3 weeks in NOD.HET or NOD.KO cell recipients and only 60% became diabetic, suggesting a role for T-cell iPLA2. Next, to establish importance of iPLA2 in CD4 or CD8 cells, purified cells were administered to NOD.scid mice. …
The Role Of Tissue- And Cell-Type-Specific Expression And Regulation In Setbp1-Associated Diseases, Jordan Hailey Whitlock
The Role Of Tissue- And Cell-Type-Specific Expression And Regulation In Setbp1-Associated Diseases, Jordan Hailey Whitlock
All ETDs from UAB
SET binding protein 1 (SETBP1) encodes a transcription factor (TF) participating in diverse cellular processes. SETBP1 is an epigenetic hub associated with variants linked to three distinct diseases. Germline variants cause rare pediatric Schinzel Giedion Syndrome (SGS) and SETBP1 haploinsufficiency disorder (SETBP1-HD), featuring multisystemic abnormalities and neurodegeneration or milder brain issues with hypotonia, respectively. On the other hand, somatic variants contribute to hematological malignancies and adult cancer. To understand tissue-specific SETBP1 mechanisms, public RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project were analyzed. SETBP1 and targets were broadly expressed across 31 adult human tissues, revealing three distinct expression patterns: transcription …
Nox2-Derived Superoxide And Mda5-Dependant Responses Contribute To Autoimmune Diabetes, Samuel Isaac Blum
Nox2-Derived Superoxide And Mda5-Dependant Responses Contribute To Autoimmune Diabetes, Samuel Isaac Blum
All ETDs from UAB
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), …
The Role Of The Bone Marrow Microenvironment In Flt3-Itd Acute Myeloid Leukemia Stem Cell Resistance To Flt3 Inhibition, Nicholas R. Anderson
The Role Of The Bone Marrow Microenvironment In Flt3-Itd Acute Myeloid Leukemia Stem Cell Resistance To Flt3 Inhibition, Nicholas R. Anderson
All ETDs from UAB
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 …
Analysing The Structural Dynamics Of Retinoid X Receptor Using Hydrogen Deuterium Exchange Mass Spectrometry, Nathalia Melo
Analysing The Structural Dynamics Of Retinoid X Receptor Using Hydrogen Deuterium Exchange Mass Spectrometry, Nathalia Melo
All ETDs from UAB
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. …
Elucidating The Role Of Stat4 In Cd4 T Cell Mediated Pathogenicity, Ashlyn E. Anderson
Elucidating The Role Of Stat4 In Cd4 T Cell Mediated Pathogenicity, Ashlyn E. Anderson
All ETDs from UAB
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 …
Targeting The Frataxin Transcriptional Defect As A Therapeutic Approach For Friedreich's Ataxia, Anna Maria Schreiber
Targeting The Frataxin Transcriptional Defect As A Therapeutic Approach For Friedreich's Ataxia, Anna Maria Schreiber
All ETDs from UAB
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 …
Molecular Mechanism And Impact Of Sox2 Regulation By The Transforming Growth Factor-Ss Members In Ovarian Cancer Survival And Metastasis, Zainab Shonibare
Molecular Mechanism And Impact Of Sox2 Regulation By The Transforming Growth Factor-Ss Members In Ovarian Cancer Survival And Metastasis, Zainab Shonibare
All ETDs from UAB
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 …
The Role Of Nitric Oxide And Cyclic Guanosine Monophosphate Signaling In Arteriovenous Fistula Maturation, Maheshika S. Somarathna
The Role Of Nitric Oxide And Cyclic Guanosine Monophosphate Signaling In Arteriovenous Fistula Maturation, Maheshika S. Somarathna
All ETDs from UAB
Vascular access is the single most important component of the hemodialysis procedure and the arteriovenous fistula (AVF) is the most preferred type. However, 60% of AVFs created fail to mature successfully for dialysis use (AVF maturation failure). AVF maturation failure is primarily the result of 1) intimal hyperplasia formation (IH) and 2) poor vascular outward remodeling. Currently, a major unmet clinical need in the field is the lack of effective therapies to treat/prevent AVF maturation failure due to the poor understanding of molecular mechanisms. This proposal is designed to: 1) elucidate the pathologic significance of nitric oxide (NO) and cyclic …
Characterization Of The Phenotype And Functional Properties Of Myeloid Subpopulations In Chronic Inflammatory Conditions, Krystle Leandra Ong
Characterization Of The Phenotype And Functional Properties Of Myeloid Subpopulations In Chronic Inflammatory Conditions, Krystle Leandra Ong
All ETDs from UAB
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 …
Applying Pet Imaging To Cancer Immunotherapy To Improve Clinical Outcomes, Kirsten M. Reeves
Applying Pet Imaging To Cancer Immunotherapy To Improve Clinical Outcomes, Kirsten M. Reeves
All ETDs from UAB
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
The Identification And Phenotypic Characterization Of Circulating Flagellin Antigen-Specific Cd4+ T Cells In Crohn's Disease Patients, Nadine N. Morgan
All ETDs from UAB
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 …
Disease And Diet-Induced Disruption Of Effector T Cell Homeostasis, Patrick Axel Molina
Disease And Diet-Induced Disruption Of Effector T Cell Homeostasis, Patrick Axel Molina
All ETDs from UAB
Homeostatic departure is a central feature across all diseases and disease processes. Currently, the average individual in the US consumes an inordinate quantity of salt. However, it is unclear if only individuals that have proven blood pressure elevation with an acute load of salt should be wary. Here we demonstrate, alongside a growing body of science, that the canonical definition of salt-sensitivity is insufficient. We show that salt-resistant mice demonstrate salt-sensitivity in non-blood pressure focused phenomena, such as the acute activation of CD4+ T cells to mobilize and induce a defective effector cytokine program with high salt. We demonstrate that …
The Roles Of Repressive And Activating Epigenetic Factors In Vertebrates Neural And Neural Crest Development, Saeid Mohammad Parast
The Roles Of Repressive And Activating Epigenetic Factors In Vertebrates Neural And Neural Crest Development, Saeid Mohammad Parast
All ETDs from UAB
The vertebrate nervous system comes from specific regions of the ectoderm that comprises of the neural plate and the neural crest. Although genetic mechanisms governing vertebrate neural development have been investigated in depth, there is a knowledge gap regarding the roles of epigenetic mechanisms in this process. As epigenetic modulators, the COMPASS (also known as SET1/MLL complex) and HP1 proteins are responsible for regulating chromatin accessibility to transcription factors. COMPASS is responsible for deposition of activating histone H3K4 methylation marks at promoters and enhancers and thus creates open chromatin domains. The critical structural and regulatory subunits of COMPASS, Dpy30 and …
Regulation Of Stromal Cells Through Inflammatory Signalling, Victoria Matkins
Regulation Of Stromal Cells Through Inflammatory Signalling, Victoria Matkins
All ETDs from UAB
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 …
Primary Cilia Regulate Inflammation And Macrophage Accumulation During Injury And Cyst Formation In Mouse Pkd Models, Zhang Li
All ETDs from UAB
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 …
Roles Of Chemokine Receptors In T Cell Accmulation In Omental Tumors, Mingyong Liu
Roles Of Chemokine Receptors In T Cell Accmulation In Omental Tumors, Mingyong Liu
All ETDs from UAB
The omentum is an adipose tissue in the peritoneal cavity that contains immune aggregates termed milky spots. Functionally similar to conventional lymphoid tissues, these specialized leukocyte clusters harbor effector and suppressor cells, mount immune responses to antigens, and sustain peritoneal homeostasis. However, the pre-existing leukocytes fail to protect the tissue from tumor colonization. In fact, the omentum is frequently involved in peritoneal metastasis, during which the balance between effector and suppressor immune cells is compromised with the latter gaining dominance. Regulatory T cells (Tregs) represent a major immunosuppressive population in the omentum and rapidly accumulate after tumor implantation. The increased …
Elucidating Pgc-1Α And Errγ Gene Regulation In Neurons, Kathlene Lanphear Joyce
Elucidating Pgc-1Α And Errγ Gene Regulation In Neurons, Kathlene Lanphear Joyce
All ETDs from UAB
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 …
Determining The Impact Of Immune Dysregulation On Cd4 T Cell Responses To Hiv-1 And Sars-Cov-2, Jacob K. Files
Determining The Impact Of Immune Dysregulation On Cd4 T Cell Responses To Hiv-1 And Sars-Cov-2, Jacob K. Files
All ETDs from UAB
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 …
The Role Of Protein Translation And Degradation In Aging And Alzheimer Disease Pathogenesis, Harper S. Kim
The Role Of Protein Translation And Degradation In Aging And Alzheimer Disease Pathogenesis, Harper S. Kim
All ETDs from UAB
Protein translation (PT) is an essential cellular process playing crucial roles in growth and development. PT precipitously declines with age in multiple animal species, including humans. It has been implicitly assumed that elevated PT at young ages is beneficial to health while PT ends up dropping as a passive byproduct of aging. However, whether this holds true and how dynamic fluctuations in PT over time impact aging remain unknown. In Drosophila, we show that a transient PT spike in early-adulthood drives aging by triggering dysfunction in protein homeostasis (proteostasis) at old ages. We propose the early-adulthood spike in PT to …
Characterizing The Role Of Tissue-Specific Retinol Dehydrogenases, Kelli Rae Goggans
Characterizing The Role Of Tissue-Specific Retinol Dehydrogenases, Kelli Rae Goggans
All ETDs from UAB
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 …
Transcriptional Regulation Of Metabolism And Synaptic Function In Neurons, Stephanie N. Fox
Transcriptional Regulation Of Metabolism And Synaptic Function In Neurons, Stephanie N. Fox
All ETDs from UAB
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 …
Epigenetic Regulation Of Gene Expression In Temporal Lobe Epilepsy, Rebecca Mary Hauser
Epigenetic Regulation Of Gene Expression In Temporal Lobe Epilepsy, Rebecca Mary Hauser
All ETDs from UAB
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 …