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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

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 …


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

All ETDs from UAB

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.


Modular Regulation And Function Of The Polypyrimidine Tract Binding Protein 1 (Ptbp1), Christine Carico Jan 2023

Modular Regulation And Function Of The Polypyrimidine Tract Binding Protein 1 (Ptbp1), Christine Carico

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RNA binding proteins (RBPs) are critical regulators of gene expression as they are responsible for the chaperoning and processing of every nascent RNA transcript. Many studies have investigated mechanisms of specificity of RBP function and have identified factors such as cell-specific expression of RBPs and differential preferences for RNA secondary structure. However, RBPs are often multi-domain proteins that contain repeats of various RNA binding domains (e.g., RNA recognition motif) and little work in the genomic era of transcriptomic interrogation has been done to define the contribution of individual domains to the overall protein function. Polypyrimidine tract binding protein 1 (PTBP1) …


Sialylation Of Epidermal Growth Factor Receptor By The Sialyltransferase St6gal1 Modulates Receptor Activity And Downstream Signaling, Katherine Ankenbauer Jan 2023

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. …


Impact Of Streptococcus Parasanguinis-Generated Reactive Nitrogen Species On Pseudomonas Aeruginosa Virulence And The Host Response, Joshua J. Baty Jan 2023

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 …


Epigenetic Aberrations In Systemic Sclerosis And Systemic Lupus Erythematosus, Peter C. Allen Jan 2023

Epigenetic Aberrations In Systemic Sclerosis And Systemic Lupus Erythematosus, Peter C. Allen

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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 …


Manipulation And Dependence On Host Cell Cycle By Human Rna And Dna Viruses: Human Coronavirus Oc43 And Bk Polyomavirus, Jason M. Needham Jan 2023

Manipulation And Dependence On Host Cell Cycle By Human Rna And Dna Viruses: Human Coronavirus Oc43 And Bk Polyomavirus, Jason M. Needham

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Cell cycle is a universal necessity of cellular life and impacts nearly every process within the cell. However, despite over one hundred years of research, there still remain questions concerning the mechanisms and regulation of eukaryotic cell cycle. From the beginning, viruses have informed our knowledge of cell cycle. Many key regulators such as the E2F transcription factors, Src kinase, and p53 were originally discovered while studying the interactions between viruses and the cell. Herein, we continue the investigation of viral interactions with cell cycle machinery by researching an RNA virus and a DNA virus. These viruses, human coronavirus OC43 …


The Molecular And Structural Basis Of B Cell Epitope Targeting In Transplant Rejection, John T. Killian Jr Jan 2023

The Molecular And Structural Basis Of B Cell Epitope Targeting In Transplant Rejection, John T. Killian Jr

All ETDs from UAB

HLA-reactive antibodies (HLA-Abs) to mismatched polymorphic HLA molecules are one of the major barriers to successful organ transplantation. However, key knowledge gaps remain surrounding the immunology of the anti-HLA B cell response in transplant rejection. This lack of understanding regarding the phenotype and specificity of the anti- HLA B cell response means that the field cannot develop optimal therapies to treat B-cell mediated donor-specific responses and that it lacks the tools to optimally match donors and recipients to prevent rejection events. Therefore, this dissertation aimed to explore the clinical factors associated with the formation of donor-specific antibodies and the molecular …


Imaging Nanoscale Plasma Membrane Dynamics Reveals Diversity In Clathrin-Coated Vesicle Formation, Tomasz Jacek Nawara Jan 2023

Imaging Nanoscale Plasma Membrane Dynamics Reveals Diversity In Clathrin-Coated Vesicle Formation, Tomasz Jacek Nawara

All ETDs from UAB

Clathrin-mediated endocytosis (CME) is an essential cellular process facilitating the internalization of a variety of cargo. Clathrin polymerization and changes in plasma membrane architecture and composition are necessary steps to mediate the formation of clathrin-coated vesicles (CCVs). However, simultaneous analysis of clathrin dynamics and membrane structure in living cells is challenging due to the limited axial resolution of fluorescence microscopes and the heterogeneity of CME. This has fueled conflicting models of vesicle assembly and obscured the roles of flat clathrin assemblies. Here we use Simultaneous Two-wavelength Axial Ratiometry (STAR) microscopy to bridge this critical knowledge gap by quantifying the nanoscale …


Reduction Of Sphingomyelinases Associated With Progranulin Deficiency And Frontotemporal Dementia, Nicholas R. Boyle Jan 2023

Reduction Of Sphingomyelinases Associated With Progranulin Deficiency And Frontotemporal Dementia, Nicholas R. Boyle

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Frontotemporal dementia (FTD) is a leading cause of early-onset dementia and has a significant socioeconomic burden due to difficulties in diagnosis and delay to diagnosis. FTD is a clinically, pathologically, and genetically heterogeneous disorder. The pathological changes associated with FTD are termed frontotemporal lobar degeneration (FTLD). Protein aggregates are always present in FTLD, with >90% of cases presenting with either TDP-43 or tau pathology. Most cases of FTD are sporadic, but familial cases account for up to 25% of FTD. All familial FTD is inherited in an autosomal dominant fashion with most cases being caused by mutations in tau (MAPT), …


Neutrophil Heterogeneity And Alternative Granulopoiesis In Chronic Inflammatory Conditions, Ashley N. Connelly Jan 2023

Neutrophil Heterogeneity And Alternative Granulopoiesis In Chronic Inflammatory Conditions, Ashley N. Connelly

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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 …


Characterizing A Unique Oprm1 Expressing Neuronal Population In The Rat Nucleus Accumbens, Emma Andraka Jan 2023

Characterizing A Unique Oprm1 Expressing Neuronal Population In The Rat Nucleus Accumbens, Emma Andraka

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Opioid-related overdose deaths have increased drastically in the past three decades, and especially since the beginning of the COVID-19 pandemic, due to the addictive, analgesic, and euphoric properties of the drugs. To produce these effects, opioids bind to the mu opioid receptor (MOR) in GABAergic neurons. The MOR is encoded by the Oprm1 gene and is expressed in multiple brain regions that regulate reward and motivation, such as the nucleus accumbens (NAc). Previous studies of Oprm1 knockdown in medium spiny neurons (MSNs) of the mouse NAc have shown that these neuronal populations are involved in reinforcing reward-context pairing as well …


The Effects Of Cannabidiol On Brain Temperature In Treatment-Resistant Epilepsy, Ayushe A. Sharma Jan 2023

The Effects Of Cannabidiol On Brain Temperature In Treatment-Resistant Epilepsy, Ayushe A. Sharma

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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 Jan 2023

Cis-Regulatory Elements: Relevance For Alzheimer's Disease, Brianne Brazell Rogers

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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 …


Time-Restricted Feeding Attenuates Obesity-Induced Muscle Dysfunction Through Energy Metabolism And Microbiota Modulation, Chris Livelo Jan 2023

Time-Restricted Feeding Attenuates Obesity-Induced Muscle Dysfunction Through Energy Metabolism And Microbiota Modulation, Chris 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 …


Impact Of Exercise On Antioxidative-Stress Induced Endoplasmic Reticulum Dysfunction And Cardiac Remodelling, Arun Jyothidasan Jan 2023

Impact Of Exercise On Antioxidative-Stress Induced Endoplasmic Reticulum Dysfunction And Cardiac Remodelling, Arun Jyothidasan

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The gain of function of nuclear factor erythroid 2 like 2 (Nrf2), in the absence of oxidative stress (or toxic insults), its pathophysiology arising from the endoplasmic reticulum and exercise intervention to mitigate the pathology are the focal point of this dissertation. Nrf2, when constitutively expressed, has been previously associated with cardiomyopathy. Chapter II investigated the hypothesis that cardiac-specific expression of Nrf2 (mNrf2-TG) would establish a pro-reductive state and trigger adaptive cardiac remodeling by enhancing the basal antioxidant defense. Through RNA profiling and imaging techniques, the study underscored that while acute preconditioning might prove advantageous against oxidative stress, prolonged pro-reductive …


The Roles Of Repressive And Activating Epigenetic Factors In Vertebrates Neural And Neural Crest Development, Saeid Mohammad Parast Jan 2022

The Roles Of Repressive And Activating Epigenetic Factors In Vertebrates Neural And Neural Crest Development, Saeid Mohammad Parast

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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 …


Roles Of Chemokine Receptors In T Cell Accmulation In Omental Tumors, Mingyong Liu Jan 2022

Roles Of Chemokine Receptors In T Cell Accmulation In Omental Tumors, Mingyong Liu

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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 …


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

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

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


Understanding The Protumorigenic Functions Of St6gal1 In Glioblastoma Stemness And Metabolism, Sajina Gc Jan 2022

Understanding The Protumorigenic Functions Of St6gal1 In Glioblastoma Stemness And Metabolism, Sajina Gc

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Glioblastoma (GBM) is a rare but deadly cancer with median survival of just 15 months despite of aggressive treatment. Advancement in novel treatment modalities is hindered by its heterogeneous nature, which includes subsets of neural stem cell-like brain tumor initiating cells (BTICs) that are highly tumorigenic and therapy-resistant. bgalactoside a-2,6-sialyltransferase 1 (ST6Gal1) is elevated in most tumors including in normal and neoplastic stem cells. ST6Gal1 imparts oncogenic phenotypes such as invasion, apoptosis evasion, therapy resistance, TIC maintenance among others via sialylation of critical receptors like, Fas, TNFR1, EGFR and more. Yet ST6Gal1 led regulation of BTIC specific cell surface proteins …


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

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

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


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

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

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


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

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

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


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

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

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