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Full-Text Articles in Medicine and Health Sciences
Investigating The P53 Tumor-Suppressive Network And The Dynamics/Mechanism Of P53 Loss Of Heterozygosity, Jun Wang
All ETDs from UAB
Tumor suppressor gene TP53 is the most frequently mutated gene across human cancers (~50%). Patients with Li-Fraumeni syndrome (LFS) who carry germline p53 mutations exhibit a diverse spectrum of childhood- and adult-onset malignancies. Despite over 40 years of dedicated studies to understand the role of p53 in tumor prevention, there are still many unanswered questions regarding the underlying mechanisms of p53. Previous studies have supported the notion that p53 exerts its tumor-suppressive function through its transcriptional activities. Therefore, strategies to enhance p53’s functions in tumor suppression via manipulating of downstream target gene activities in cancers show promising. To better investigate …
A Tale Of Two Waves: The Role Of Genomic Enhancers In Regulating Transcriptional And Epigenetic Responses To Neuronal Activitiy, Robert A. Phillips Iii
A Tale Of Two Waves: The Role Of Genomic Enhancers In Regulating Transcriptional And Epigenetic Responses To Neuronal Activitiy, Robert A. Phillips Iii
All ETDs from UAB
The mesolimbic dopamine (DA) pathway, which consists of dopaminergic neurons that project from the ventral tegmental area (VTA) to the nucleus accumbens (NAc), is heavily implicated in drug addiction. Exposure to drugs of abuse results in increases in extracellular concentrations of DA in the NAc, which in turn activates an immediate early gene (IEG) expression program that primarily consists of activity-dependent transcription factors, such as the AP1 subunits Fos and JunB. IEGs engage a set of temporally and functionally distinct genes, termed the late response gene (LRG) expression program. While gene expression changes are critical for drug-dependent adaptations, two major …
Understanding Molecular Mechanisms Of Glioblastoama Resistance To Design Novel Combinatorial Therapies, Amber B. Jones
Understanding Molecular Mechanisms Of Glioblastoama Resistance To Design Novel Combinatorial Therapies, Amber B. Jones
All ETDs from UAB
Treatment options for the universally lethal brain tumor, glioblastoma (GBM), are severely limited and often unsuccessful in fully eradicating the disease. Extremely aggressive in nature, GBM cells often implore suppressive mechanisms to evade therapeutic detection which aids in the dismal 15-month median survival rate. Facilitating disease severity and more importantly, disease recurrence, are the immunosuppressive and chemoresistant phenotypes of GBM cells. Specifically, the DNA alkylating agent, temozolomide (TMZ) possesses lymphodepleting properties shunting robust immune cell infiltration into an immunologically cold tumor microenvironment. Additionally, through inherent or acquired mechanisms, GBM tumors commonly become resistant to the DNA damaging effects of TMZ …
Unveiling The Molecular Features Of Cancer Health Differences Through Multi-Omics Data Analysis, Fengyuan Huang
Unveiling The Molecular Features Of Cancer Health Differences Through Multi-Omics Data Analysis, Fengyuan Huang
All ETDs from UAB
Understanding the molecular features underlying cancer health differences is crucial for developing effective therapeutic strategies. Multi-omics data analysis, integrating various molecular layers such as genomics, transcriptomics, epigenomics, proteomics, and metabolomics, provides a comprehensive approach to characterize the molecular landscape of cancer differences. By integrating diverse omics data, researchers can identify genetic variations, gene expression patterns, epigenetic modifications, and protein alterations that contribute to differences in cancer progression, and treatment response. These molecular features can serve as potential biomarkers for predicting patient outcomes and guiding personalized treatment strategies. Furthermore, multi-omics data analysis enables the identification of molecular subtypes specific to different …
Spatial/Temporal Zonation, Diversification, And Evolutionary Conservation Of Kidney Resident Macrophage Subpopulations In Mice And Humans After Kidney Injury, Elise Nicole Erman
Spatial/Temporal Zonation, Diversification, And Evolutionary Conservation Of Kidney Resident Macrophage Subpopulations In Mice And Humans After Kidney Injury, Elise Nicole Erman
All ETDs from UAB
In the United States, acute kidney injury (AKI) affects nearly 20% of all intensive care unit patients. Additionally, over a third of Americans aged 50 or older suffer from stage 3 chronic kidney disease (CKD) or higher. AKI and CKD are encompassing terms for many etiologies and pathological processes that affect different regions of the kidney but converge at tissue inflammation and fibrosis. Macrophages perform vital homeostatic functions and can initiate or ameliorate inflammation and fibrosis. As the largest component of the kidney immune system, kidney resident macrophages (KRMs) have been implicated in both disease propagation and mitigation, yet the …
Application Of Machine Learning And Network Approaches To Prioritize Safe And Efficacious Drug Repurposing Candidates, Jennifer L. Fisher
Application Of Machine Learning And Network Approaches To Prioritize Safe And Efficacious Drug Repurposing Candidates, Jennifer L. Fisher
All ETDs from UAB
Only ten percent of drugs in clinical trials are ultimately approved by the Food and Drug Administration (FDA). With many diseases and disorders needing therapeutic options, computational drug repurposing methodologies are great alternatives to some drug discovery methods due to quicker FDA approval and lower cost. We sought to gain insights to improve the identification of drug repurposing candidates that will be safe and effective to increase the success of computational drug repurposing approaches. In regards to identifying safe drug candidates, pharmacovigilance studies of adverse event case reports identified that women are more likely to experience an adverse event, and …
Impact Of Streptococcus Parasanguinis-Generated Reactive Nitrogen Species On Pseudomonas Aeruginosa Virulence And The Host Response, Joshua J. Baty
Impact Of Streptococcus Parasanguinis-Generated Reactive Nitrogen Species On Pseudomonas Aeruginosa Virulence And The Host Response, Joshua J. Baty
All ETDs from UAB
Streptococcus parasanguinis is an oral commensal bacterium that produces hydrogen peroxide. Hydrogen peroxide can react with endogenous molecules such as nitrite to form reactive nitrogen intermediates (RNI). These S. parasanguinis-mediated RNI have been shown to inhibit oral pathogens such as Streptococcus mutans, Enterococcus faecalis, and Aggregatibacter actinomycetemcomitans. As such, S. parasanguinis plays a protective role in the oral microbial ecosystem by antagonizing and preventing colonization by oral pathogens. In addition to being an important organism for the health of the oral cavity, S. parasanguinis has also been associated with improved outcomes for people with cystic fibrosis. There are two explanations …
Sialylation Of Epidermal Growth Factor Receptor By The Sialyltransferase St6gal1 Modulates Receptor Activity And Downstream Signaling, Katherine Ankenbauer
Sialylation Of Epidermal Growth Factor Receptor By The Sialyltransferase St6gal1 Modulates Receptor Activity And Downstream Signaling, Katherine Ankenbauer
All ETDs from UAB
During the process of malignant transformation, cells have striking changes in their cell surface glycosylation. One of these changes is an enrichment for α2,6 sialic acid which is added by the sialyltransferase, ST6GAL1. ST6GAL1 is upregulated in numerous malignancies and acts by adding an α2,6 sialic acid onto receptors bound for the plasma membrane. This sialic acid, in turn, modulates the activity of the receptor by regulating conformation, clustering, and cell surface retention. The work presented in this dissertation focuses on how ST6GAL1-mediated sialylation of a specific cell surface receptor, epidermal growth factor receptor (EGFR), regulates many of its properties. …
Epigenetic Aberrations In Systemic Sclerosis And Systemic Lupus Erythematosus, Peter C. Allen
Epigenetic Aberrations In Systemic Sclerosis And Systemic Lupus Erythematosus, Peter C. Allen
All ETDs from UAB
Autoimmune diseases are a classification of more than eighty diseases where the immune system recognizes a self-antigen and mistakenly attacks the body’s own tissue, inducing inflammation a nd p otentially l eading t o d amage. Autoimmune diseases disproportionately affect women and develop at any age depending on the disease. The prevalence of some autoimmune diseases is increased in minority populations. Despite this, research into higher-risk populations is lacking. This highlights the need to contribute research into understanding autoimmune disease pathogenesis in diverse studies to understand why disease is more severe in these populations. We analyzed transcriptomes and methylomes of …
Neutrophil Heterogeneity And Alternative Granulopoiesis In Chronic Inflammatory Conditions, Ashley N. Connelly
Neutrophil Heterogeneity And Alternative Granulopoiesis In Chronic Inflammatory Conditions, Ashley N. Connelly
All ETDs from UAB
Neutrophils, the most abundant type of circulating leukocyte, represent a heterogeneous population with distinct roles in immune regulation and disease pathogenesis. A major obstacle to our understanding of neutrophil biology is that neutrophils are readily activated during preparation. The lack of standardized methodology for neutrophil characterization makes the comparison of results across studies challenging. Here we provide a careful comparison of eight characterization methods and present a novel, optimized protocol for the characterization of whole blood neutrophils minimizing activationinduced phenotypic alterations during processing. Despite successful virological control, HIV-1-infected individuals maintain an increased risk of life-threatening comorbidities including liver, cardiovascular, and …
The Effects Of Cannabidiol On Brain Temperature In Treatment-Resistant Epilepsy, Ayushe A. Sharma
The Effects Of Cannabidiol On Brain Temperature In Treatment-Resistant Epilepsy, Ayushe A. Sharma
All ETDs from UAB
Epilepsy affects over 70 million people worldwide with a global incidence of 2.4 million new cases per year. In many of these patients, neuroinflammation (NI) is a key pathological contributor to focal seizure generation and maintenance. Sustained NI degrades the blood–brain barrier, leads to neuronal death, and ultimately decreases seizure threshold. Finding ways to image and treat NI is especially important for the >30% of patients with treatment-resistant epilepsy (TRE) who cannot achieve seizure freedom with standard antiseizure medications. Cannabidiol (CBD) effectively reduces seizure frequency and severity in many TRE patients, although its antiepileptic effects remain poorly understood. Atypically high …
Cis-Regulatory Elements: Relevance For Alzheimer's Disease, Brianne Brazell Rogers
Cis-Regulatory Elements: Relevance For Alzheimer's Disease, Brianne Brazell Rogers
All ETDs from UAB
Alzheimer’s disease (AD) is the most common neurodegenerative disease, currently affecting more than six million Americans with limited treatment options. Identifying genetics contributors to neurodegenerative diseases has contributed critical insights into potential disease mechanisms. The majority of disease-associated genetic variants are located in non-coding regions, likely in regulatory elements, and affect the expression of target genes whose function contributes to neurodegeneration. Here, I performed a case-control study utilizing nuclei from dorsolateral prefrontal cortex postmortem tissue to correlate chromatin accessibility with gene expression and nominate 40,831 AD-specific candidate cis-regulatory elements. Additionally, work in this dissertation nominates ZEB1 and MAFB as candidate …
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 …
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 …
The Requirement Of Transcriptional Lim Complex Co-Regulators For Pancreatic Endocrine Cell Development And Function, Eliana Davi Toren
The Requirement Of Transcriptional Lim Complex Co-Regulators For Pancreatic Endocrine Cell Development And Function, Eliana Davi Toren
All ETDs from UAB
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 …
Molecular Imaging Of Cancer For Detection And Monitoring Of Response To Combination Therapy, Tiara S. Napier
Molecular Imaging Of Cancer For Detection And Monitoring Of Response To Combination Therapy, Tiara S. Napier
All ETDs from UAB
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
Cell Type-Specific Diurnal Variation In Hippocampus Physiology, Lacy Kathryn Goode
All ETDs from UAB
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 …
Synergy Between Stenotrophomonas Maltophilia And Pseudomonas Aeruginosa During Polymicrobial Airway Infections, Melissa Skye Mcdaniel
Synergy Between Stenotrophomonas Maltophilia And Pseudomonas Aeruginosa During Polymicrobial Airway Infections, Melissa Skye Mcdaniel
All ETDs from UAB
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 …
Three Heads Are Better Than One: A Structural Look At Staphylococcal Bacteriophage Capsids, N'Toia Chivon Hawkins
Three Heads Are Better Than One: A Structural Look At Staphylococcal Bacteriophage Capsids, N'Toia Chivon Hawkins
All ETDs from UAB
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 …
Hedgehog Signaling Rewires M2 Macrophage And Regulatory T Cell Metabolism Within The Tumor Microenvironment Of Breast Cancer, Dominique C. Hinshaw
Hedgehog Signaling Rewires M2 Macrophage And Regulatory T Cell Metabolism Within The Tumor Microenvironment Of Breast Cancer, Dominique C. Hinshaw
All ETDs from UAB
Current treatments for breast cancer offer little relief to patients with metastatic disease. A contributory factor to tumor growth and metastasis is aberrant up-regulation of developmental signaling pathways such as the Hedgehog (Hh) signaling pathway. This pathway is aberrantly activated in breast cancer and contributes to tumor progression and metastasis. The success of these events is highly influenced by the surrounding immune microenvironment. Macrophages exist along a spectrum of M1 (tumor-eradicating) to M2 (tumor-promoting), while regulatory T cells (Tregs) are an immunosuppressive cell type. The predominant functions of M2 macrophages and Tregs include dampening the immune response and promoting wound …
Comprehensive Characterization Of Structural Variations Using Long-Read Sequencing Data, Yu Chen
Comprehensive Characterization Of Structural Variations Using Long-Read Sequencing Data, Yu Chen
All ETDs from UAB
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 …
Defining Genetic Underpinnings Of Cellular Diversity And Vulnerability In The Context Of Parkinson's Disease, Stephanie M. Boas
Defining Genetic Underpinnings Of Cellular Diversity And Vulnerability In The Context Of Parkinson's Disease, Stephanie M. Boas
All ETDs from UAB
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
Distinct Clinical Manifestations Associated With Autoantibodies And Cytokines In Systemic Lupus Erythematosus, Fatima K. Alduraibi
All ETDs from UAB
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
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), …
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 …
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. …
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, Krystla Leandra Ong
Characterization Of The Phenotype And Functional Properties Of Myeloid Subpopulations In Chronic Inflammatory Conditions, Krystla 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 …