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Evaluating Fty720 As An Anticancer Agent In Models Of Ovarian Cancer, Kelly Marie Kreitzburg
Evaluating Fty720 As An Anticancer Agent In Models Of Ovarian Cancer, Kelly Marie Kreitzburg
All ETDs from UAB
Despite satisfactory initial responses to frontline therapies that combine tumor debulking with platinum and taxane-based chemotherapies, ovarian cancer remains the principle cause of gynecological malignancies. Drug resistance at relapse contributes to poor outcomes for women diagnosed with advanced disease and underscores the need for novel therapeutic strategies. Compelling data have implicated bioactive sphingolipids and their metabolism in the development and progression of ovarian cancer. Aberrations in sphingolipid metabolism that limit levels of the tumor suppressor lipid ceramide contribute to chemotherapy resistance. This dissertation presents work investigating the anticancer efficacy of the immunomodulatory drug FTY720. The sphingosine analog FTY720 has shown …
An Investigation Of Sla Class Ii As A Xenoantigen, Joseph Ladowski
An Investigation Of Sla Class Ii As A Xenoantigen, Joseph Ladowski
All ETDs from UAB
Xenotransplantation, using genetically-modified pigs as organ donors, is a potential solution to the growing transplant organ shortage. Avoiding antibody-mediated rejection (AMR) is the remaining hurdle to widespread application. The development of a triple glycan knockout pig reduced antibody binding to clinically acceptable levels, allowing for the screening of the history of antibodies to the major histocompatibility complex (MHC). In allotransplantation, the MHC is a group of proteins divided into two classes and anti-MHC antibodies possess the ability to cause both acute and chronic AMR. The pig MHC, the swine leukocyte antigen (SLA), is a hypothesized target of antibodies. This dissertation …
Apoe E4 Carrier Status And Prestroke Cognitive Function In A Case/Cohort Sample Of Incident Stroke From The Reasons For Geographic And Racial Differences In Stroke (Regards) Study, Caroline Lassen-Greene
Apoe E4 Carrier Status And Prestroke Cognitive Function In A Case/Cohort Sample Of Incident Stroke From The Reasons For Geographic And Racial Differences In Stroke (Regards) Study, Caroline Lassen-Greene
All ETDs from UAB
This study explores the role of ApoE e4 in cognitive function and incident stroke to better understand the risk of cognitive decline associated with both normal aging and dementia. ApoE e4 is a genetic risk factor for mild cognitive impairment and dementia, and may have detrimental effects on cerebrovascular integrity by increasing the risk of acquiring cerebrovascular abnormalities such as white matter lesions (WMLs), infarcts, and cerebral microbleeds. Subtle cognitive impairments may reflect these clinically undetected brain vascular pathologies that also are associated with increased likelihood of incident stroke. Results of the study revealed that ApoE e4 was associated with …
Effectiveness Of A Robot Social Skills Therapy For Children With An Autism Spectrum Disorder, Jenna Brooke Lebersfeld
Effectiveness Of A Robot Social Skills Therapy For Children With An Autism Spectrum Disorder, Jenna Brooke Lebersfeld
All ETDs from UAB
This study examined the effectiveness of a robot-based social skills intervention for school-age children with Autism Spectrum Disorder (ASD) across a range of cognitive ability. Sixteen children were assigned to either the intervention group (n = 8), which received the robot intervention, or a control group (n = 8), which played non-emotion games with the robot. All participants reported high levels of enjoyment, motivation, and willingness to have future robot interaction sessions, indicating that the robot intervention is engaging and interesting for this population. However, there was no difference between groups on measures of emotion identification or generalized social skills. …
The Mechanism Of Tobacco-Induced Decrements In Mucociliary Clearance, Vivian Lin
The Mechanism Of Tobacco-Induced Decrements In Mucociliary Clearance, Vivian Lin
All ETDs from UAB
Chronic obstructive pulmonary disease (COPD), characterized by progressive loss of lung function including mucus obstruction and airway remodeling, is primarily caused by cigarette smoking. This pulmonary phenotype resembles that of cystic fibrosis (CF), which results from genetic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an ion channel important in maintaining airway surface hydration and mucus clearance. Cigarette smoke exposure has been found to induce acquired CFTR dysfunction, leading to airway dehydration, abnormal mucin production, and impaired mucus transport. Smoke exposure also induces mucus hypersecretion and ciliary dysfunction; together, these changes result in defective mucus clearance and subsequent muco-obstruction. …
Bone Marrow Transplantation In A Mouse Model Of Cooley’S Anemia, Jonathan Russell Lockhart
Bone Marrow Transplantation In A Mouse Model Of Cooley’S Anemia, Jonathan Russell Lockhart
All ETDs from UAB
β-thalassemia is a group of inherited blood disorders that result in defects in β-globin chain production. Cooley’s anemia (CA), or β-thalassemia major, is the most severe form of the disease and occurs when an individual has mutations in both copies of the adult β-globin gene. Patients with CA fail to make adult hemoglobin, have ineffective erythropoiesis, suffer from severe anemia, and are transfusion dependent for life. Currently, allogeneic bone marrow transplantation (BMT) is the only cure; however, few patients have suitable donors for this procedure that carries a significant risk of morbidity and mortality. To develop new and safer alternatives …
Lick My Battery, Sasha Mitchell
Lick My Battery, Sasha Mitchell
All ETDs from UAB
An insecure cyborg named Grit defects to a tech-atheist society. Her neuro-disorder-addicted sister, Siri, follows her with a licentious government drone, one officer Rah Tetra of the Austere Sapien Services (A.S.S. for short). Sex, anthropology, family dysfunction, and social rigidity are tackled beneath the influences of Radiohead, Billy Wilder, and Jonathan Swift.
Inception Of A Cellulose Nitrate-Layered Silicate Nanocomposite Coating: Study Of The Formulation Procedure, Degree Of Dispersion, Coating Properties, And Uv Stability, Precious Mitchell
Inception Of A Cellulose Nitrate-Layered Silicate Nanocomposite Coating: Study Of The Formulation Procedure, Degree Of Dispersion, Coating Properties, And Uv Stability, Precious Mitchell
All ETDs from UAB
Cellulose nitrate lacquer is a coating system that is used in the conservation of silver art pieces in museums. This coating degrades prematurely in the presence of extensive light exposure, which is prominent in display cases, thus comprising the surface of the art piece. When facing this fact, it is imperative to create a new polymer coating system with an in-crease in barrier properties so that the life expectancy of the coating increases. The synthesis of a cellulose nitrate-layered silicate nanocomposite coating stands to enhance the barrier properties of cellulose nitrate through proper dispersion of layered silicates. A proper formulation …
The Relationship Of Cognitive Decline And Impairment To The Ad8 And Activities Of Living In The Regards Sample, Jesse S. Passler
The Relationship Of Cognitive Decline And Impairment To The Ad8 And Activities Of Living In The Regards Sample, Jesse S. Passler
All ETDs from UAB
The AD8 is a sensitive and specific screening measure of mild dementia, although less research exists pertaining to its use as a self-report measure and in non-clinical samples. This study examined the relationship of incident cognitive impairment and cognitive decline over a 10-year span to self-reported dementia symptoms and functional impairment in the national, population-based, longitudinal, and prospective REasons for Geographic and Racial Differences in Stroke (REGARDS) sample (N = 14,453). A validated cutoff of ≥ 2 symptoms endorsed on the AD8 was used for dementia status. Functional status was determined by 5 activities of daily living (ADL) and 7 …
T Cell Immunity Directed Against Novel Anti-Sense Cryptic Epitopes And Its Impact On Hiv Viral Evolution, Binghao Jason Peng
T Cell Immunity Directed Against Novel Anti-Sense Cryptic Epitopes And Its Impact On Hiv Viral Evolution, Binghao Jason Peng
All ETDs from UAB
After nearly four decades of scientific research, a global solution in eradicating the human immunodeficiency virus - 1 (HIV-1) pandemic has still yet to be discovered. The advent of antiretroviral therapies (ART) has significantly decreased the diseases burden for those infected with the virus; however, the access to ART is often limited to those with the financial abilities to afford it. For this reason, finding a way to vaccinate against HIV-1 successfully remains a sought-after pragmatic solution to this worldwide health issue. HIV immunological studies have taught us that increasing the breadth of response to the virus holds significant potential …
Mucus Adhesion As A Therapeutic Target In Cystic Fibrosis, Courtney Fernandez Petty
Mucus Adhesion As A Therapeutic Target In Cystic Fibrosis, Courtney Fernandez Petty
All ETDs from UAB
Cystic fibrosis (CF) is a genetic disease resulting from mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR is an ion channel responsible for proper movement of chloride and bicarbonate ions across the apical cell surface. Defective CFTR results in an absence of bicarbonate transport, which functions in part to chelate Ca2+, a divalent cation found in abundance in mucin granules in normal conditions; this yields a hyperviscous and adhesive mucus on the respiratory and gastrointestinal tracts of patients with CF. Bronchial mucins are glycosylated proteins with neutral and negative sugars modified by negatively charged sialic and neuraminic …
The Influence Of Treatment Expectation On Transcranial Direct Current Stimulation (Tdcs)-Induced Suppression Of Craving And Eating, Mary Katherine Osborn Ray
The Influence Of Treatment Expectation On Transcranial Direct Current Stimulation (Tdcs)-Induced Suppression Of Craving And Eating, Mary Katherine Osborn Ray
All ETDs from UAB
Transcranial direct current stimulation (tDCS) is a neuromodulation technique with promise to improve numerous diseases, but results are inconsistent. Possible explanations for the conflicting evidence include: 1) expectation effects arising from discernable real vs. sham tDCS conditions, and 2) uncontrolled individual differences related to the outcome variables. Therefore, we conducted a study that systematically assessed the putative action of tDCS to suppress food craving and eating while controlling for expectation effects and baseline individual differences. N=74 adults were randomized to one of four groups: Told Fake/Got Fake (participants were told they were receiving fake and received fake tDCS), Told Fake/Got …
The Effect Of Novel Antibiotic Compounds On Endodontic Biofilms, Steven Rhodes
The Effect Of Novel Antibiotic Compounds On Endodontic Biofilms, Steven Rhodes
All ETDs from UAB
Purpose: To investigate the effects of three novel experimental antibiotics on monospecies (Enterococcus faecalis) and polymicrobial (mixed) endodontic biofilms. Materials and Methods: Biofilms containing pure Enterococcus faecalis, as well as biofilms derived from mixed bacterial samples aspirated from inside the pulp spaces of necrotic human teeth, were grown onto slices of human dental in vitro. Biofilm formation capability was verified with SEM. The treatment groups consisted of 3 novel experimental antibiotics. 8.25% sodium hypochlorite and sterile saline were used as the controls. The biofilms were investigated with live/dead fluorochrome staining and confocal laser scanning microscopy. Results: The full strength sodium …
The Effects Of Ketamine And Other Rapid Antidepressants On Hippocampal Circuits, Allie J. Widman
The Effects Of Ketamine And Other Rapid Antidepressants On Hippocampal Circuits, Allie J. Widman
All ETDs from UAB
Major Depressive Disorder (MDD) in a common mental disorder that can impair cognitive functioning and negatively impact hippocampus. While several pharmacological treatments are currently available for MDD, most target the monoamine system, providing little variety in approaching treatment. Additionally, a large percentage of people with MDD have an inadequate response to this drug class, leaving them with little optimism of a full functional recovery. Recently, low-dose ketamine, an open-channel N-methyl D-aspartate receptor (NMDAR) antagonist, produced rapid antidepressant effects in humans, including people who do not respond to monoamine-based therapies, that lasted for days. The antidepressant-like behavioral effect of ketamine is …
Novel Anti-Cancer Therapy Development Using Omics Guided Rational Cell Process Engineering, Ningning Xu
Novel Anti-Cancer Therapy Development Using Omics Guided Rational Cell Process Engineering, Ningning Xu
All ETDs from UAB
Cancer is one of the leading causes of mortality globally, and multiple anti-cancer therapies have been developed and applied over last few decades. Antibody-based cancer therapies have been on one of the most exciting and promising therapeutic strategies. Monoclonal antibodies (mAbs) can control the progression of cancers via targeted binding to the specific antigen of tumors to trigger an immune response, target and block the signaling pathway involved in cancer progression, or deliver cytotoxic agents into tumors. Two chimeric/humanized monoclonal antibodies (anti-HER2 mAb and anti-CD 20 mAb) with higher efficacy were successfully expressed in engineered Chinese Hamster Ovary Cells (CHO). …
Effects Of Dietary R,S-1,3 Butanediol Diacetoacetate On Components Of Energy Balance, Rachel A H Davis
Effects Of Dietary R,S-1,3 Butanediol Diacetoacetate On Components Of Energy Balance, Rachel A H Davis
All ETDs from UAB
Ketogenic diet (KD) has been used to attenuate the decline in energy expenditure occurring from calorie restriction-induced weight loss, but long-term adherence can be difficult due to the strict nature of the diet. The growing body of evidence supporting KD-treatment of neurologic and metabolic diseases, as well as obesity, has prompted interest in the ability to increase circulating ketones via exogenous delivery. Ketone esters (KE) can raise blood ketone concentrations similarly to fasting and appear to reduce food intake acutely, but studies assessing effects on energy balance are limited and provide a potentially promising direction for weight control. Previous investigations …
Elucidating The Role Of Hedgehog Signaling In Modulating Macrophage Function In Breast Cancer, Ann Hanna
Elucidating The Role Of Hedgehog Signaling In Modulating Macrophage Function In Breast Cancer, Ann Hanna
All ETDs from UAB
In the tumor microenvironment, breast cancer cells participate in crosstalk with the surrounding stroma. This tumoral-stromal interaction forms a balance that dictates tumor suppressing or tumor promoting response mechanisms. Macrophages in the tumor microenvironment are plastic and can mediate several functions depending on their activation states. Tumor associated macrophages co-exist as two major phenotypes: anti-tumorigenic and immune-eliciting classically activated M1 as well as tumor-promoting and immune-suppressive alternatively activated M2 macrophages. Alternatively activated macrophages are specifically associated with more aggressive stages and poor clinical outcomes in breast cancer patients as they suppress the tumoricidal properties of the immune system, thus facilitating …
Applications Of Next-Generation Sequencing And Functional Genomics In Translational Medicine, Andrew Hardigan
Applications Of Next-Generation Sequencing And Functional Genomics In Translational Medicine, Andrew Hardigan
All ETDs from UAB
The development of next-generation sequencing (NGS) technologies has led to unparalleled advances in our understanding of the genetic basis of disease, evolution, and genetic and genomic regulation. Building on the advances made in the Human Genome Project and more recent efforts such as the Encylopedia of DNA Elements (ENCODE) and the Roadmap Epigenomics Project, whole-genome and whole-exome sequencing (WGS/WES) and a wide variety of NGS-enabled functional assays are bridging the gap between scientific discovery and clinical medicine. This trend towards genomically informed “bench-to-bedside” translational medicine is driven in large part by the sharply decreasing costs for NGS in both clinical …
Human Neurobiology Following Trauma: Assessing Brain Function, Structure, And Biochemistry, Nathaniel Gene Harnett
Human Neurobiology Following Trauma: Assessing Brain Function, Structure, And Biochemistry, Nathaniel Gene Harnett
All ETDs from UAB
Approximately 25 million United States (U.S.) citizens experience a potentially traumatic event each year, and almost 90% of the U.S. population will experience at least one traumatic event in their lifetime. Trauma exposure is the primary antecedent to the development of Post-Traumatic Stress Disorder (PTSD), a highly debilitating mental health disorder characterized by chronic cognitive-affective dysfunction. However, there is considerable variability in susceptibility to PTSD. Specifically, trauma exposure may result in PTSD for one person, but not another. Therefore, a better understanding of the acute processes that affect brain function, structure, and biochemistry following trauma exposure is critical for the …
Evaluation Of The Factors Influencing Feed Intake And Satiety Of The Variegated Sea Urchin, Lytechinus Variegatus, Marlee Hayes
Evaluation Of The Factors Influencing Feed Intake And Satiety Of The Variegated Sea Urchin, Lytechinus Variegatus, Marlee Hayes
All ETDs from UAB
Feed intake is the primary determinant of nutrient and energy acquisition for most metazoans. Satiety regulates feed intake and may have cascading effects on nutrient acquisition and health. Satiety of many higher organisms involves complex processes and a variety of signaling molecules that are responsive to many factors associated with nutrient intake. However, the ability to sate is observed in many simpler animals with less complex physiological processes. Sea urchins, with relatively simple digestive and nervous systems, provide an ideal model for the study of fundamental drivers of feed intake. Understanding the process of satiety in this primitive deuterostome can …
The Biomimetic Cardiac Tissue Model, Aaron Joseph Rogers
The Biomimetic Cardiac Tissue Model, Aaron Joseph Rogers
All ETDs from UAB
Every year about 735,000 Americans will suffer a heart attack and 1 in 4 will end up dying from heart disease. Study of this disease has been impacted by the limited availability of appropriate human cell types. The discovery of human induced pluripotent stem cells (hiPSCs) and development of protocols to differentiate these cells into cardiomyocytes (hiPSC-CM) has enabled study into this disease free from ethical dilemma, and reliance on animal models. Unfortunately, hiPSC-CMs are immature in nature and closely resemble fetal or neonatal cardiomyocytes. We hypothesized that hemodynamic stimuli, missing from static cultures, would allow us to mature hiPSC-CMs …
Epigenetic Regulation Of Stem Cell Fate Determination And Tumorigenesis, Kushani Shah
Epigenetic Regulation Of Stem Cell Fate Determination And Tumorigenesis, Kushani Shah
All ETDs from UAB
It is unclear how H3K4 methylation, an epigenetic modification associated with gene activation, regulates stem cell fate determination and tumorigenesis. DPY30 is one of the core subunits of the SET1/MLL complex in mammals responsible for H3K4me. DPY30 enhances the H3K4me activity of the SET1/MLL complex. Here, I sought to define role of DPY30 and H3K4me3 in postnatal neurogenesis and hematopoietic malignancies. Using a conditional knockout model, I found that Dpy30 deficiency halts the development of postnatal hippocampus, the subventricular zone, and cerebellum. Deficiency in cerebellum is most likely the cause of uncoordinated ataxia-like movements in these mice. By deleting Dpy30 …
Regulation Of Effector Cd4 T Cell Pathogenicity During Chronic Inflammation, Boyoung Shin
Regulation Of Effector Cd4 T Cell Pathogenicity During Chronic Inflammation, Boyoung Shin
All ETDs from UAB
Effector CD4 T cells are essential for the balance between pro- and anti-inflammatory immune responses during homeostasis. Dysregulation of effector CD4 T cell responses results in chronic inflammatory disorders such as Inflammatory Bowel Disease (IBD) and Multiple Sclerosis (MS), however therapeutic options for these diseases are limited. Understanding the mechanisms that regulate pathogenicity of effector CD4 T cells is critical to devise new therapeutic interventions. Herein we show two different mechanisms that profoundly impact pathogenic potential of CD4 T cells by regulating heterogeneities of effector functions and differentiation states. Different subsets of effector CD4 T cells utilize distinct metabolic pathways. …
Autophagy In Mitochondrial Quality Control And Proteotoxicity In Neurons, Matthew Redmann
Autophagy In Mitochondrial Quality Control And Proteotoxicity In Neurons, Matthew Redmann
All ETDs from UAB
Parkinson’s disease (PD) is the 2nd most common neurodegenerative disorder with aging as a significant risk factor. Sharing with aging brains, postmortem PD brains exhibit cellular deficits including autophagic dysfunction, mitochondrial dysfunction, and intracellular protein aggregates of alpha-synuclein. This dissertation will focus on the interplay between these key disease features. To that end, we coupled primary cortical neuronal cultures from either rats or mice with Seahorse extracellular flux, metabolomics and biochemical techniques. Autophagy is an important cell recycling program responsible for the clearance of damaged proteins and organelles. Bafilomycin A1 and chloroquine are compounds that inhibit autophagy by targeting the …
Osteoblast And Chondrocyte Specific Contribution Of The Runx2 Gene During The Development Of Cleidocranial Dysplasisa, Kayla Renee King
Osteoblast And Chondrocyte Specific Contribution Of The Runx2 Gene During The Development Of Cleidocranial Dysplasisa, Kayla Renee King
All ETDs from UAB
The Runx2 transcription factor is essential for the differentiation of mesenchymal stem cells into functional chondrocytes and osteoblasts. In humans, the haploinsufficiency of the Runx2 gene is associated with cleidocranial dysplasia (CCD). The CCD is characterized by short stature, open sutures and fontanels in the skull, hypoplastic clavicles and supernumerary teeth. Skeletal elements disrupted in CCD patients are developed by intramembranous and/or endochondral ossification. However, the cell type specific roles of the Runx2 gene in the development of CCD-associated skeletal defects remain unknown. The main goal of this research was to define the specific role of the Runx2 gene in …
The Role Of Hur In Astrocytes In Spinal Cord Injury, Thaddaeus Kwan
The Role Of Hur In Astrocytes In Spinal Cord Injury, Thaddaeus Kwan
All ETDs from UAB
Neuroinflammation is a defining event during the acute phase of spinal cord injury (SCI). The inflammatory cascade is initiated by activated glial cells such as astrocytes and microglia in the milieu of the injured tissue through release of pro-inflammatory cytokines, matrix metalloproteinases, and reactive oxygen species. These soluble factors produce cytotoxicity to neurons and other cells either directly or indirectly by promoting permeabilization of the blood-spinal cord barrier, edema and subsequent ischemia. These factors also serve to recruit and activate additional glia and peripheral immune cells. The mRNAs of many of these soluble factors such as TNFα, IL-1β, CXCL1, and …
Investigating Gender Differences In The Metabolism Of Ketamine, Elise Erb
Investigating Gender Differences In The Metabolism Of Ketamine, Elise Erb
All ETDs from UAB
Ketamine is a dissociative anesthetic that was developed for use as a short-acting anesthesia. It has a history of being a drug of abuse and is currently a Schedule III drug. Ketamine is being investigated as an antidepressant due to its fast-action and long-lasting effects in comparison to other antidepressants. The exact mechanism of action of ketamine on the brain that results in the antidepressant effects is currently unknown, as is the reason for differences in the way males and females respond to ketamine. Dr. Lori McMahon, Allie Widman, and Nateka Jackson in the Cell, Developmental, and Integrative Biology Department …
The Function Of Protein Kinase Ck2 In Cd4 T Cell Differentiation And Autoimmunity, Sara Ann Gibson
The Function Of Protein Kinase Ck2 In Cd4 T Cell Differentiation And Autoimmunity, Sara Ann Gibson
All ETDs from UAB
Protein kinase CK2 is a highly conserved serine/threonine kinase essential for cell viability. CK2 exhibits immense pleiotropy and has well characterized interactions with canonical cytosolic signaling pathways such as PI3K/Akt/mTOR and JAK/STAT. These pathways are critical for CD4+ T cell function, and further are known to be aberrantly active in the T cell-driven autoimmune disease Multiple Sclerosis, but little is known as to how CK2 functions in CD4+ T cells or in the context of autoimmune diseases. The current dissertation examines the understudied T cell-specific functions of CK2 utilizing two approaches, pharmacologic inhibition and genetic deletion. We discovered CK2 to …
Marine, Jennifer Danielle Glassford
Marine, Jennifer Danielle Glassford
All ETDs from UAB
Marine is a nonfiction work written as memoir. Major themes coursing through this body of work include family, fear of failure, self-awareness, self-reliance and female empowerment.
Associations Among Perceived Stress, Pain Sensitivity, And Physiological Reactivity Following An Acute Noxious Stressor, Hailey Waddell Bulls
Associations Among Perceived Stress, Pain Sensitivity, And Physiological Reactivity Following An Acute Noxious Stressor, Hailey Waddell Bulls
All ETDs from UAB
We recommend using HCCM estimators to estimate the variance of a regression model