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Application Of Machine Learning And Network Approaches To Prioritize Safe And Efficacious Drug Repurposing Candidates, Jennifer L. Fisher Jan 2023

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 …


Pharmacologic Proteasome Activators Ameliorate Alzheimer's-Like Pathology In Ad Fly Models, Mehar Bano Jan 2023

Pharmacologic Proteasome Activators Ameliorate Alzheimer's-Like Pathology In Ad Fly Models, Mehar Bano

All ETDs from UAB

The proteasome is a large multi-subunit protease responsible for the degradation and removal of oxidized, misfolded, and polyubiquitinated proteins. The proteasome plays a critical role in nervous system processes. This includes the maintenance of cellular homeostasis in neurons (1). It also includes synaptic efficacy and plasticity as well as protein turnover, presynaptic vesicle transport, and neuronal protesostasis. Proteasome function is impaired as a consequence of aging, which is aggravated by conditions like Alzheimer's Disease and Related-Dementias (AD, ADRD) (2). According to earlier work from our lab the proteasome is critical to how quickly AD progresses. In Drosophila, human cells, and …


Understanding Molecular Mechanisms Of Glioblastoama Resistance To Design Novel Combinatorial Therapies, Amber B. Jones Jan 2023

Understanding Molecular Mechanisms Of Glioblastoama Resistance To Design Novel Combinatorial Therapies, Amber B. Jones

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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 …


Expression Of St6gal1 Imparts Stem-Like Cell Behaviors, Thereby Promoting Neoplasia, Sejal Sanjay Shinde Jan 2023

Expression Of St6gal1 Imparts Stem-Like Cell Behaviors, Thereby Promoting Neoplasia, Sejal Sanjay Shinde

All ETDs from UAB

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most lethal malignancies with a five-year survival of ~10%. Recent studies in the US population suggest PDAC as the fourth leading cause of cancer-related deaths in 2022. ST6 β-galactoside α2,6-sialyltransferase (ST6GAL1) is a glycosyltransferase which is known to be upregulated in cancer. It acts as a master regulator of a cell by being the predominant sialyltransferase catalyzing the addition of a bulky negatively charged sialic acid to the galactose sugar in an α2,6-linkage. Due to this, the sialic acid changes the structure and function of cell surface receptor proteins and regulates signal …


Investigating The Effects Of Immune Checkpoint Inhibition And Combined Treatment With Evofosfamide On The Tumor Microenvironment Through Hypoxia Imaging, Kaytlyn Carter Mcneal Jan 2023

Investigating The Effects Of Immune Checkpoint Inhibition And Combined Treatment With Evofosfamide On The Tumor Microenvironment Through Hypoxia Imaging, Kaytlyn Carter Mcneal

All ETDs from UAB

Colorectal cancer (CRC) is a prevalent and deadly cancer worldwide. While immunotherapy, particularly immune checkpoint inhibition, shows promise in various cancers, its efficacy in CRC and other tumor types is limited. Hypoxia, characterized by inadequate tissue oxygenation, critically drives cancer progression, promoting tumor growth, metastasis, chemotherapy resistance, and poor prognosis. Evofosfamide, a hypoxia-activating prodrug, is being evaluated in clinical trials for combined use with checkpoint blockade as a potential therapeutic strategy. This study investigates the impact of hypoxia on immune checkpoint inhibition, evofosfamide, and combination therapy, while utilizing non-invasive molecular imaging to develop analytical methods for quantifying and characterizing tumor …


Sex-Stratified Genetic Analysis Of Gout And Comorbidities, Nicholas Andrew Sumpter Jan 2023

Sex-Stratified Genetic Analysis Of Gout And Comorbidities, Nicholas Andrew Sumpter

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Gout is a common inflammatory arthritis that is increasing in prevalence globally. It has clear sex differences, being more common among men, though comorbidities appear to be more common among women. It also varies in prevalence between populations, driven by a combination of genetic and socioeconomic factors. Genetic studies have identified gout-associated genetic variants, several of which are shared between different populations. Here, I combined gout-associated genetic variants into a gout polygenic risk score. This score was then used to elucidate the genetic underpinning of gout severity and presence of comorbidities, comparing its effects in different sexes and populations. I …


Unveiling The Molecular Features Of Cancer Health Differences Through Multi-Omics Data Analysis, Fengyuan Huang Jan 2023

Unveiling The Molecular Features Of Cancer Health Differences Through Multi-Omics Data Analysis, Fengyuan Huang

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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 Jan 2023

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 …


Chronic Circadian Disruption Increases Risk For Cardiovascular Disease, Jazmine I Benjamin Jan 2023

Chronic Circadian Disruption Increases Risk For Cardiovascular Disease, Jazmine I Benjamin

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Circadian disruption is a disturbance in biological timing which can occur within or between different organizational levels, ranging from molecular rhythms within specific cells to misalignment of behavioral and environmental cycles. Previous work has shown that changing the timing of food availability is sufficient to lower blood pressure and improve insulin sensitivity in prediabetic males, demonstrating the importance of timing of food intake for cardiovascular health. Findings from our group demonstrated that less than one week of mistimed feeding is sufficient to invert diurnal blood pressure rhythms, although kidney excretory rhythms and kidney function remained aligned with the light-dark cycle. …


Regulatory Elements Of Polyphosphate Biosynthesis, Marvin Qortez Bowlin Jan 2023

Regulatory Elements Of Polyphosphate Biosynthesis, Marvin Qortez Bowlin

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Polyphosphate (polyP) is an ancient, conserved, inorganic biomolecule. Biological systems have adapted many functions for this high-energy molecule, ranging from immune regulation in mammals to gene regulation in prokaryotes. Of particular interest is its use in bacterial stress responses. Bacteria use polyP to resist hazardous environmental elements like toxic molecules or nutrient starvation. In many bacterial species, polyP is synthesized by polyphosphate kinases (PPKs). PPK – discovered in Escherica coli (E. coli) – hydrolyzes adenosine-5’-triphosphate (ATP) to synthesize polyP. Species that use PPK develop multiple pathogenic defects when PPK activity is impaired, including, among others, antibiotic susceptibility. There is no …


Challenges And Opportunities In Glioblastoma And Immunovirotherapy With Oncolytic Herpes Simplex Virus Type 1, Dagoberto Estevez-Ordonez Jan 2023

Challenges And Opportunities In Glioblastoma And Immunovirotherapy With Oncolytic Herpes Simplex Virus Type 1, Dagoberto Estevez-Ordonez

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This dissertation covers data from published and pre-published studies exploring challenges and opportunities in the treatment of malignant glioma with emphasis in glioblastoma and oncolytic immunovirotherapy with an oncolytic herpes simplex virus type 1 (HSV-1) designed to induce expression of IL-12, M002 (murine IL-12) and M032 (human IL-12).It starts with the report of a study that uncovered important racial and socioeconomic disparities experienced by patients with glioblastoma treated in Alabama. Notable results also include the unexpected finding of increased survival in African American patients with glioblastoma even after controlling for factors associated with survival and socioeconomic disparities. The implications of …


The Influence Of Proximity On Patient Outcomes For Differently Structured Ambulatory Surgery Centers, Wendy Michelle Smith Jan 2023

The Influence Of Proximity On Patient Outcomes For Differently Structured Ambulatory Surgery Centers, Wendy Michelle Smith

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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 …


Neuropeptide Y Overexpression In The Presence Of P23h Rhodopsin Mutation, Jean Sun Jan 2023

Neuropeptide Y Overexpression In The Presence Of P23h Rhodopsin Mutation, Jean Sun

All ETDs from UAB

Neuropeptide Y (NPY), a 36-amino acid peptide, has been found to be the most abundant neuropeptide in the central nervous system, and it is widespread across mammalian species. NPY plays a dual role as a neurotransmitter and neuromodulator in the nervous system. NPY functions as a multifaceted neuromodulator through binding NPY receptors (NPYRs). NYP interacts with NPYRs and regulates various activities, such as cell growth, neurogenesis, neuroprotection, mitochondrial behaviors, food intake, anxiety, and addiction formation. In terms of NPY’s neuroprotective potential, NPY inhibits neuronal death signaling, thus preventing apoptosis, and displays anti-inflammatory and anti-oxidative effects. Additionally, it influences metabolism by …


Select Lipid Signaling. Derived From T-Cells Is An Important Contributor To Type 1 Diabetes Development, Tayleur White Jan 2023

Select Lipid Signaling. Derived From T-Cells Is An Important Contributor To Type 1 Diabetes Development, Tayleur White

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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. …


Chronic Hiv Infection Influences The Immune Response To Sars-Cov-2, Skye Opsteen Jan 2023

Chronic Hiv Infection Influences The Immune Response To Sars-Cov-2, Skye Opsteen

All ETDs from UAB

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused global morbidity and mortality since late 2019. Many infections result in self-limited disease and recovery in 1-2 weeks. However, a subset of individuals experience more severe illness, associated with hospitalization, ventilation, and potential mortality. HIV infection is a proposed risk factor for more severe illness due to people living with HIV (PLWH) experiencing chronic immune activation and inflammation despite effective antiretroviral therapy. While there is supporting evidence showing worsened clinical outcomes in PLWH experiencing acute COVID-19, the immune response driving these outcomes is less explored. We analyzed markers of immune activation …


Uncovering The Role Of Spt5 In Rna Polymerase I Transcription Through Targeted Protein Degradation Via The Auxin Inducible Degron System In Saccharomyces Cerevisiae, Nathan Bellis Jan 2023

Uncovering The Role Of Spt5 In Rna Polymerase I Transcription Through Targeted Protein Degradation Via The Auxin Inducible Degron System In Saccharomyces Cerevisiae, Nathan Bellis

All ETDs from UAB

RNA Polymerases are the molecular machines responsible for the synthesis of RNA from the DNA template. The presence of these machines is an absolute requirement for the function and replication of all cellular organisms. In eukaryotic organisms, there are a minimum of three RNA polymerases (Pols I, II, II). Despite shared subunits and homology, these three protein complexes are functionally distinct, with many unique sub-units and additional trans-acting factors. Pol I is responsible for the synthesis of three of the four ribosomal RNA species which is the first and rate limiting step of ribosome biogenesis. Pol I synthesizes the majority …


Early Life Stress And Endothelin Receptor Type A: Separate Roles In Mediating Colitis, Rachel Q. Muir Jan 2023

Early Life Stress And Endothelin Receptor Type A: Separate Roles In Mediating Colitis, Rachel Q. Muir

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Inflammatory bowel disease (IBD) results from the interplay of genetic susceptibility, environmental influences, the microbiota, and aberrant immune responses. Despite the fact that over 200 genetic susceptibility loci have been identified, the genetic contribution to disease onset is believed to be less than 50%. Environmental factors have arisen as key drivers of disease. Early life stress (ELS) is an understudied environmental trigger linked to IBD susceptibility. Utilizing 2 separate models of ELS, we show that ELS results in diminished colonic corticosterone and prolonged intestinal inflammation upon colitogenic insult. ELS-exposed animals consistently demonstrated high levels of colonic Tnf, concurrently with decreased …


Differential Mechanisms Of Intestinal Inflammation Drive Pathogenesis Of Diabetic Retinopathy In Type 1 And Type 2 Diabetes, Jason Levi Floyd Jan 2023

Differential Mechanisms Of Intestinal Inflammation Drive Pathogenesis Of Diabetic Retinopathy In Type 1 And Type 2 Diabetes, Jason Levi Floyd

All ETDs from UAB

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and, along with diabetic macular edema (DME), accounts for the greatest source of vision-threatening eye disease in the working-age community. DR is caused by weakening of the retinal vasculature, the blood-retinal barrier (BRB), by high levels of blood glucose (hyperglycemia), exacerbations of oxidative stress, and systemic inflammatory factors. Many of these inflammatory factors are metabolic by-products and cell membrane constituents of the gut microbiota, the resident community of microbial species which inhabit the lumen of the gastrointestinal tract. These factors are collectively termed gut microbial antigens (GMAs). In diabetes, …


Biochemical Characterization Of Rna Polymerases I, Ii, And Iii And Its Therapeutic Implications, Ruth Qian Jacobs Jan 2023

Biochemical Characterization Of Rna Polymerases I, Ii, And Iii And Its Therapeutic Implications, Ruth Qian Jacobs

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In contrast to Bacteria and Archaea that express a single DNA-dependent RNA polymerase (RNAP), eukaryotes express at least three structurally distinct, nuclear, DNA-dependent RNA polymerases (Pols I, II, and III) that are responsible for synthesizing all the genome-encoded RNA required by the cell. Despite the discovery of the Pols over 50 years ago, there remains a knowledge gap concerning their enzymatic properties. Over the course of evolution, we know that Pols I, II, and III have diverged in structure and function. They share a 10-subunit core and are each responsible for transcribing unique genetic loci. What remains to be understood …


Regulating Cancer Cell Metabolism During Hypoxia-Reoxygenation: Examing The Interplay Of Gasotransmitters And Glutaminolysis, Dianna L. Xing Jan 2023

Regulating Cancer Cell Metabolism During Hypoxia-Reoxygenation: Examing The Interplay Of Gasotransmitters And Glutaminolysis, Dianna L. Xing

All ETDs from UAB

Oxidative phosphorylation is an oxygen-dependent metabolic process that provides the majority of ATP used to support essential cellular functions. However, in cancer, limitations in oxygen availability occur during the development and metastasis of tumors. To compensate for the demands of rapidly proliferating cells, many cancers exhibit an increased demand for glycolysis, the TCA cycle, and glutaminolysis. In this thesis, extracellular flux technology and metabolomics were applied in a hypoxia-reoxygenation model to investigate the metabolic adaptations that occur in dynamic changes in oxygen and nutrient availability in cancer cells. We show the significance of glutaminolysis and its substrates in regulating cancer …


Interactions Between Pseudomonas Aeruginosa And The Oral Commensal Streptococcus Salivarius, Sara Noelle Stoner Jan 2023

Interactions Between Pseudomonas Aeruginosa And The Oral Commensal Streptococcus Salivarius, Sara Noelle Stoner

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The cystic fibrosis airway is a polymicrobial environment often dominated by opportunistic pathogens such as Pseudomonas aeruginosa, a leading cause of lung function decline and mortality in persons with CF. Commensal streptococcal colonization has been associated with stable CF lung function in multiple studies. However, few studies have examined interactions between P. aeruginosa and commensals as well as their impact on P. aeruginosa airway infections. In the first half of this work, we studied interactions between P. aeruginosa and the oral commensal Streptococcus salivarius within a biofilm setting. We found that S. salivarius biofilm formation is promoted by the non-mucoid …


Investigating The P53 Tumor-Suppressive Network And The Dynamics/Mechanism Of P53 Loss Of Heterozygosity, Jun Wang Jan 2023

Investigating The P53 Tumor-Suppressive Network And The Dynamics/Mechanism Of P53 Loss Of Heterozygosity, Jun Wang

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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 Jan 2023

A Tale Of Two Waves: The Role Of Genomic Enhancers In Regulating Transcriptional And Epigenetic Responses To Neuronal Activitiy, Robert A. Phillips Iii

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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 …


Dact1, The “Super-Crosslinker”: Regulation Of Non-Canonical Wnt Signaling During Vertebrate Convergent Extension By Modulating Dishevelled Oligomerization, Allyson Angermeier Jan 2023

Dact1, The “Super-Crosslinker”: Regulation Of Non-Canonical Wnt Signaling During Vertebrate Convergent Extension By Modulating Dishevelled Oligomerization, Allyson Angermeier

All ETDs from UAB

A broad spectrum of human birth defects arise from the disruption of morphogenesis, the critical process through which tissues and organs acquire their proper shape. Convergent extension (CE) is a universal morphogenetic engine that promotes polarized extension of diverse tissues and organs by regulating directional cell behavior, such as oriented cell intercalation. In vertebrates, CE is regulated by non-canonical Wnt/Planar Cell Polarity (PCP) pathway, an ancient signaling pathway that was originally discovered to coordinate the cellular polarity in the plane of the epithelium. Non-canonical Wnt/PCP signaling shares the Frizzled (Fz) receptor and cytoplasmic signal transducer Dishevelled (Dvl) with the canonical …


Crucial Role Of T Follicular Helper Cell-Derived Ifn-Γ In Lung Resident Memory B Cell Responses, Nicole Michelle Arroyo-Diaz Jan 2023

Crucial Role Of T Follicular Helper Cell-Derived Ifn-Γ In Lung Resident Memory B Cell Responses, Nicole Michelle Arroyo-Diaz

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T follicular helper (Tfh) cells constitute a distinct subset of CD4 T cells that reside within B cell follicles, playing an indispensable role in orchestrating the Germinal Center (GC) response. In response to polarizing environments, such as Influenza A virus infection (IAV), Tfh cells secrete effector cytokines, including IFN-γ and IL-4. Nevertheless, the specific functions of cytokine-producing Tfh cell subsets, beyond their involvement in driving class switch recombination (CSR), remain largely unexplored. Here, we demonstrate that, following IAV infection, Tfh cell cytokine production undergoes a dynamic shift, transitioning from early IFN-γ dominance to later predominance of IL-4. The initial IFN-γ …


The Role Of Tissue- And Cell-Type-Specific Expression And Regulation In Setbp1-Associated Diseases, Jordan Hailey Whitlock Jan 2023

The Role Of Tissue- And Cell-Type-Specific Expression And Regulation In Setbp1-Associated Diseases, Jordan Hailey Whitlock

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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 …


Aberrant Signal Transduction Of Neuronal Injury: Trauma And Toxicology, Alan Umfress Jan 2023

Aberrant Signal Transduction Of Neuronal Injury: Trauma And Toxicology, Alan Umfress

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Neurological injuries occur in epidemic proportions worldwide. Neuronal injuries are events resulting in damage to the central nervous system (CNS) that impair neurological function. Subsequent impairments in neuronal function can be rapid, existing immediately after injury, or progressive and chronic impairments that persist for the lifetime of the survivor. CNS injury constitutes a broad class of environmental and pathophysiological insults ranging from blunt-force trauma to the brain or spinal cord, to acute ischemic and hemorrhagic strokes, and insults resultant from neurotoxic agents. While divergent in initial cause, many of these insults share underlying pathophysiological outcomes including excitotoxic cell signaling, neuroinflammation, …


Strategies For Her2 Targeted Pet Imaging, Maxwell Adams Ducharme Jan 2023

Strategies For Her2 Targeted Pet Imaging, Maxwell Adams Ducharme

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Breast cancer is one of the most common and deadly cancers diagnosed in women each year. The HER2-positive subtype of breast cancer is associated with poor prognosis and lower progression-free survival. Early identification of HER2 expression is extremely important for the effective treatment of the disease. Current methods to diagnose HER2-positive breast cancer involve invasive biopsies to semi-quantitatively determine the amount of HER2 expression. However, many lesions are often unavailable for biopsy due to their location and there may be variable HER2 expression between the primary tumor and metastasis. Positron emission tomography (PET) can give a full-body, non-invasive evaluation of …


Impact Of Arthroplasty Surgery On The Local Immune Composition Of The Knee Joint And Implications For The Periprosthetic Joint Infection, Kyle H. Cichos Jan 2023

Impact Of Arthroplasty Surgery On The Local Immune Composition Of The Knee Joint And Implications For The Periprosthetic Joint Infection, Kyle H. Cichos

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The overall risk of infection after total knee arthroplasty (TKA) has not improved over the past 20 years, remaining 10-40 times greater than the risk of infection of a native knee. Despite extensive research into periprosthetic joint infection (PJI), little is known about the synovial fluid immune homeostasis of the native knee joint and how TKA surgery itself impacts the local immune composition. While many postulate a role for cartilage in maintaining this immune homeostasis, the exact method in which it contributes remains elusive. Therefore, in this dissertation I have investigated the synovial fluid changes occurring in the knee joint …


Plasticity Characteristics Of Cxcr5+ Cd4+ T Memory Cells And Cxcr5- Non-Tfh Memory Cells, Ching-En Lee Jan 2023

Plasticity Characteristics Of Cxcr5+ Cd4+ T Memory Cells And Cxcr5- Non-Tfh Memory Cells, Ching-En Lee

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iv ability to differentiate into CXCR5- and CXCR5+ effector cells between the CCR7- and CCR7+ CXCR5+ CD4+ T memory cells, between WT and μMT CXCR5+ CD4+ T memory cells, as well as between Bcl6- and Bcl6+ CXCR5- non-Tfh memory cells. This finding did not support the hypothesis that the heterogeneous characteristics within CXCR5- non-Tfh memory cells and CXCR5+ CD4+ T memory cells significantly affect their abilities to differentiate into CXCR5- and CXCR5+ effector cells during recall responses.