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Doctor of Philosophy (PhD) Heersink School of Medicine

2021

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Full-Text Articles in Medicine and Health Sciences

The Psychological, Social, And Bioinformatic Considerations For The Return Of Continental Genetic Ancestry Estimates And Other Secondary Sequencing Results, Jaimie Leighan Richards Jan 2021

The Psychological, Social, And Bioinformatic Considerations For The Return Of Continental Genetic Ancestry Estimates And Other Secondary Sequencing Results, Jaimie Leighan Richards

All ETDs from UAB

With recent advances in sequencing technologies, large scale genome wide sequencing has advanced our understanding of disease risk and etiology. These tests, however, often provide secondary data beyond the scope of the original sequencing objectives, and our understanding of how and if participants want to receive these secondary results is important as clinical and research-based sequencing becomes commonplace. To address this, we completed a systematic review of quantitative research that measures attitudes and preferences on the return of genomic sequencing results. Based on that review, we studied the return of genetic ancestry since these results, popularized in direct-to-consumer sequencing companies …


Glycolytic Myeloid Cells Protect The Host In Tuberculosis, Hayden Thomas Pacl Jan 2021

Glycolytic Myeloid Cells Protect The Host In Tuberculosis, Hayden Thomas Pacl

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Despite curative treatment, tuberculosis remains a leading cause of death around the world. As such, there is great interest in novel therapeutic approaches to treat this disease. One such approach aims to enhance the efficacy of host immune cells in responding to the pathogen, Mycobacterium tuberculosis—so called host-directed therapies. The metabolism of immune cells has been a central focus in the search for hostdirected therapies, and the role of glycolysis in myeloid cells, in particular, has received much attention. However, the role of glycolysis in myeloid cells in the context of tuberculosis has not yet been made clear. Here we …


Heads Or Tails? Structural Studies Of Host Interaction And Molecular Piracy In Bacteriophages, James Lewis Kizziah Jan 2021

Heads Or Tails? Structural Studies Of Host Interaction And Molecular Piracy In Bacteriophages, James Lewis Kizziah

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Staphylococcus aureus is an opportunistic human pathogen dependent mainly on bacteriophages (phages) for dissemination of the virulence factors that contribute to its pathogenicity. Most phages have double-stranded DNA (dsDNA) genomes which are packaged into protein capsids attached to tails of varying morphology to form their complete virion structures. S. aureus pathogenicity islands (SaPIs) are highly specialized mobile genetic elements that encode various virulence factors and have been named molecular pirates for their ability to parasitize certain helper phages. SaPI1 is capable of hijacking virions constructed by the helper phage 80α, partly by altering the size of the capsid to only …


Upregulation Of Somatostatin Receptor 2 In Neuroendocrine Tumors Using Histone Deacetylase Inhibitors, Rachael Elizabeth Guenter Jan 2021

Upregulation Of Somatostatin Receptor 2 In Neuroendocrine Tumors Using Histone Deacetylase Inhibitors, Rachael Elizabeth Guenter

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Neuroendocrine cancer is complex disease of the diffuse neuroendocrine system. Neuroendocrine tumors (NETs) can arise throughout the body, including the lungs and pancreas. These tumors are phenotypically and genetically heterogeneous, making accurate diagnoses difficult with current imaging standards. New diagnostic options, coupled with a better understanding of neuroendocrine cancer etiology, is urgent and necessary to provide patients with better futures. Many NETs overexpress somatostatin receptor 2 (SSTR2) on their cellular surfaces, making patients eligible for [68Ga]-DOTATATE PET/CT imaging and SSTR2-based therapies. However, patients that lack sufficient SSTR2 overexpression cannot benefit from SSTR2-targeted imaging or therapeutic options. We found that histone …


Neonatal Murine Cytomegalovirus Infection Disrupts Synapse Remodeling During Development, Jerome Moulden Jan 2021

Neonatal Murine Cytomegalovirus Infection Disrupts Synapse Remodeling During Development, Jerome Moulden

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Human cytomegalovirus (HCMV) is a complex double stranded DNA betaherpesvirus. Its linear DNA in enclosed in an icosahedral capsid, and has a genome size of about 230kb and encodes about 170 genes. Primary infection with HCMV lead to a lifelong persistent infection. HCMV can also be transmitted across the placenta and infect the developing fetus leading to infection of the newborn infant, an infection which is commonly described as congenital HCMV infection. In the United States, the prevalence of congenital HCMV infection is between 0.2-1.2%. Approximately 5-15% of these newborn infants will develop long-term neurological damage resulting, motor disorder, cognition …


Experience-Dependent Plasticitiy Of Functional Connectivity In Human Visual Cortex Following Central Vision Loss, Leland Lanelle Fleming Jan 2021

Experience-Dependent Plasticitiy Of Functional Connectivity In Human Visual Cortex Following Central Vision Loss, Leland Lanelle Fleming

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The human brain is shaped by a dynamic interplay between innate factors and life experiences. Neuroscience has long grappled with understanding this relationship, particularly with regard to how changes in experience impact the brain during adulthood. This question is especially important in the context of macular degeneration, a disease that causes significant visual impairment and drastically alters day-to-day visual experiences for individuals afflicted by the disease. Specifically, people with macular degeneration lose the ability to use vision in the center of the visual field, the region of the retina with the highest spatial resolution. Subsequently, these individuals must rely on …


Regulation Of Nitric Oxide Syntahse 3 By Histone Deacetylase, Luke S. Dunaway Jan 2021

Regulation Of Nitric Oxide Syntahse 3 By Histone Deacetylase, Luke S. Dunaway

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In the vasculature, nitric oxide is produced by nitric oxide synthase 3 (NOS3) and protects against the development of cardiovascular disease (CVD). The histone deacetylases (HDACs) are a family of enzymes responsible for lysine deacetylation of both histone and non-histone proteins. Understanding how NO signaling is regulated by HDACs will allow us to better understand how HDAC inhibitors may be of use in treating CVD. This dissertation seeks to provide novel insight into the regulation of NOS3 by this family of enzymes. Endothelial NO production is impaired in human subjects and rodents fed a high salt diet (HS). We have …


The Impact Of Blimp1 On Etreg Stability And The Tumor Microenvironment, Michael Dixon Jan 2021

The Impact Of Blimp1 On Etreg Stability And The Tumor Microenvironment, Michael Dixon

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CD4+ Foxp3+ regulatory T (Treg) cells are responsible for maintaining immunological homeostasis and self-tolerance through the regulation of immune responses against foreign and self-antigens, and they comprise both central Treg and effector Treg (eTreg) subsets. Because of their ability to suppress potent immune responses, eTreg cells expressing the transcription factor Blimp1 are frequently recruited to the tumor microenvironment (TME) to suppress anti-tumor responses by tumor infiltrating effector cells. Here, we demonstrate in murine transplantable tumor models that Blimp1 is required for intratumoral eTreg stability and that loss of Blimp1 by intratumoral eTreg cells results in their reduced suppressive activity and …


Suppressing Islet Graft Rejection With Antioxidant-Based Encapsulation Materials, Jessie Marie Barra Jan 2021

Suppressing Islet Graft Rejection With Antioxidant-Based Encapsulation Materials, Jessie Marie Barra

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A hallmark of Type 1 diabetes (T1D) is the autoimmune destruction of insulin-producing pancreatic β-cells. Once the β-cells are lost, patients are reliant on less efficient exogenous insulin therapies to maintain glycemic control, leaving them at risk for secondary complications. Islet transplantation can restore the ability to regulate glucose levels without the need for exogenous insulin, however long-term islet graft survival has proven challenging in part due to ongoing immune-mediated destruction. Systemic immunosuppression strategies have proven somewhat effective at preventing rejection, but chronic use leaves the patient susceptible to opportunistic infections and organ toxicity. Reactive oxygen species (ROS), such as …


Studies On Nontypeable Haemophilus Influenzae Biofilm Persistence & Redox Homeostasis In Chronic Bacterial Diseases, Benjamin C. Hunt Jan 2021

Studies On Nontypeable Haemophilus Influenzae Biofilm Persistence & Redox Homeostasis In Chronic Bacterial Diseases, Benjamin C. Hunt

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Bacterial biofilms, or surface-adherent bacterial communities surrounded by a self-produced extracellular polymeric matrix, are ubiquitous. They are found throughout Earth’s ecosystems, in the soil and waterways, and more pressingly for the medical community, they are found within humans. Bacterial biofilms are associated with a multitude of diseases and their involvement significantly complicates treatment given that bacteria growing within a biofilm are extremely more resistant to antibiotics and immune effectors. Thus, the need to better understand biofilm biology and find ways to disrupt and/or sensitize biofilms to medical treatment is significant. The goal of the research presented herein was to investigate …


Diurnal Variation In Hippocampal Neurophysiology And Pathophysiology, Allison R. Fusilier Jan 2021

Diurnal Variation In Hippocampal Neurophysiology And Pathophysiology, Allison R. Fusilier

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Circadian rhythms are ~24-hour cycles in biological processes that are endogenously generated, entrained to light, and synchronized by the suprachiasmatic nucleus of the hypothalamus. One process that is influenced by circadian rhythms is cognitive function, which varies over the course of the day and is likely influenced by changes in neuronal physiology over the course of the day. Dysfunction in circadian rhythms has been documented in many diseases, including Alzheimer’s disease (AD). AD is a neurodegenerative disease most notably characterized by dementia, amyloid beta plaques, and tau tangles. There is currently no cure for AD, and treatments only slow disease …


Tau-Sh3 Interactions And Alzheimer's Disease, Jonathan Roth Jan 2021

Tau-Sh3 Interactions And Alzheimer's Disease, Jonathan Roth

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Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide, and its impact will increase with an aging population. It is characterized by dementia associated with accumulation of extracellular amyloid-β (Aβ) plaques, intracellular hyperphosphorylated Tau tangles, and neurodegeneration. Additionally, network hyperexcitability occurs early in AD and likely contributes to disease pathogenesis. Current therapies provide minor delay of disease progression at best, so it is imperative to develop novel therapeutic approaches to prevent and treat AD. As Tau pathology correlates better with cognitive function than Aβ pathology and Tau reduction prevents Aβ-induced dysfunction in preclinical models, targeting Tau is a growing …


Characterization Of Cellular And Viral Factors That Define The Stability Of The Latent Hiv-1 Reservoir, Eric Carlin Jan 2021

Characterization Of Cellular And Viral Factors That Define The Stability Of The Latent Hiv-1 Reservoir, Eric Carlin

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Human immunodeficiency virus (HIV) infection is a chronic viral illness that requires lifelong management due to the early formation of a latent viral reservoir within the patient’s CD4+ T cells. These latent infection events lay dormant within infected cells and reactivate stochastically or during periods of T cell activation presenting a major hurdle to the development of an HIV cure. As our understanding of the factors that contribute to HIV latency has evolved, we have started to appreciate latency as more than a chromatin regulation phenotype, due to the vast number of cellular factors that have been described to impact …


Transcriptional Regulation And Islet Transplantation Advantages Of Brown Adipose Tissue, Jessica D. Kepple Jan 2021

Transcriptional Regulation And Islet Transplantation Advantages Of Brown Adipose Tissue, Jessica D. Kepple

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Metabolic disease encompasses various disorders, including obesity and diabetes, that negatively impact glucose and lipid homeostasis and increase the risk of co-morbidities. Adipose tissue, which regulates whole-body energy balance and acts as a specialized endocrine tissue, is negatively affected by obesity and diabetes. Brown adipose tissue (BAT) functions to dissipate excess energy as heat and therefore is an attractive target against metabolic disease. To develop more effective therapeutic strategies, BAT physiology and genetic regulatory mechanisms need to be better understood. This dissertation highlights studies seeking to illuminate novel transcriptional regulation and islet transplantation applications of BAT. We investigated the requirement …


Analysing The Contribution Of Snare-Dependent Exocytosis From Astrocytes To Huntinton's Disease Pathogenesis Using The Bachd Mouse Model, Annesha C. King Jan 2021

Analysing The Contribution Of Snare-Dependent Exocytosis From Astrocytes To Huntinton's Disease Pathogenesis Using The Bachd Mouse Model, Annesha C. King

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Huntington’s disease (HD) is a dominantly inherited neurodegenerative disease caused by a polyglutamine expansion in the huntingtin protein. Multiple studies have indicated the importance of mutant huntingtin (mHTT) in astrocytes to HD pathogenesis. Increased extracellular glutamate levels were observed after evoking SNARE-dependent exocytosis from cultured mHTT expressing astrocytes. To determine whether astrocytic SNARE-dependent exocytosis contributed to behavioral and neuropathological changes in vivo, we crossed BACHD mice to dominant negative SNARE (dnSNARE) mice and analyzed behavioral and neuropathological phenotypes. First, we found that reduc-ing astrocytic SNARE-dependent exocytosis had differential effects on the psychiatric-like and motor phenotypes observed in BACHD mice where …


Understanding The Role Of Biomechanics In Ovarian Cancer Biology, Alba Martinez Diaz Jan 2021

Understanding The Role Of Biomechanics In Ovarian Cancer Biology, Alba Martinez Diaz

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Mechanical forces including compression, tension, and shear stress are increasingly implicated as instigators of tumor progression. Understanding how mechanobiology drives ovarian cancer is critical to identifying potential therapies. The effect of shear stress is beginning to be studied in ovarian cancer due to the presence of ascites in the peritoneal cavity that prompts tumor cells detachment and implantation in secondary sites. Therefore, mechanical cues are present within the peritoneal cavity. A growing ovarian tumor mass also experiences compressive and tensile forces, although their participation in tumor progression still remains unclear. Additionally, there is a specific lack of incorporation of mechanobiology …


A Role For Inf-Ɣ-Inducble Transcription Factors In Antibody Secreting Cell Differentiation, Jessica N. Peel Jan 2021

A Role For Inf-Ɣ-Inducble Transcription Factors In Antibody Secreting Cell Differentiation, Jessica N. Peel

All ETDs from UAB

Viral infections remain a major cause of morbidity and mortality. Within a viral, interferon (IFN)-ɣ-driven inflammatory microenvironment, B cells may produce antibody which is critical for rapid viral clearance and continued protection from reinfection. However, the roles of IFN-ɣ and IFN-ɣ-induced transcription factors (TFs) in driving antibody secreting cell (ASC) development from their B cell precursors are poorly understood. Herein, we identify two IFN-ɣ-inducible transcription factors (TFs), T-bet and interferon regulatory factor 1 (IRF1), that are essential for the differentiation of ASCs from IFN-g-activated B cell precursors. T-bet repressed an IFN-ɣ-inducible inflammatory gene program that was incompatible with ASC formation …


Structural Changes To Desmosomal Architecture During Assembly And Maturation, Reena R. Beggs Jan 2021

Structural Changes To Desmosomal Architecture During Assembly And Maturation, Reena R. Beggs

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Desmosomes are macromolecular junctions important in adhesion and resisting mechanical stress in epithelial and cardiac tissue. Desmosomes have a complex architecture with transmembrane cadherins, desmogleins and desmocollins, constituting the adhesive interface and plaque proteins, including plakoglobin and desmoplakin, binding the cadherin tails and integrating with intermediate filaments. Dysregulation of desmosomes occurs in many disease states, such as cardiomyopathies, skin diseases, and various cancers. While mature desmosomes' structure is generally understood, less is known about desmosome architecture during assembly and recycling. Desmosomes are dynamic, biochemically intractable, and diffraction-limited, making them challenging to study. To overcome these obstacles, I applied the super-resolution …


Beyond Apoptosis: Insight Into The Complex Intracellular Networks That Govern Cell Fate, Hayley Neal Widden Jan 2021

Beyond Apoptosis: Insight Into The Complex Intracellular Networks That Govern Cell Fate, Hayley Neal Widden

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The determination of cell fate is a dynamic process regulated by hundreds of proteins that converge into complex cell signaling pathways. Upon irreparable intracellular stress, a cell undergoes programmed cell death, a process known as intrinsic apoptosis. Apoptosis is regulated by the Bcl-2 family, a class of proteins that act either as pro-survival or pro-death signaling molecules. Due to the oncogenic upregulation of pro- survival Bcl-2 family proteins across human cancer cell types, a novel class of small molecule inhibitors called ‘BH3-mimetics’ have emerged as promising anti-cancer therapeutics currently under clinical investigation. Here, we highlight the crosstalk between anti-apoptotic Bcl-2 …


Biological Pathways And Processes Underlying The Cardiac Regenerative Response Post-Injury In Small And Large Mammals, Eric Yang Zhang Jan 2021

Biological Pathways And Processes Underlying The Cardiac Regenerative Response Post-Injury In Small And Large Mammals, Eric Yang Zhang

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Mammalian cardiomyocytes exit the cell-cycle shortly after birth. Consequently, the adult heart is unable to properly compensate for cardiac muscle lost to injury. As such, heart failure has remained the leading cause of death in the developed world for more than three decades. In this work, we illustrate our findings in using novel in-vivo animal models to examine two regenerative phenomena observed following myocardial injury:i.) neonate cardiomyocyte proliferation in large mammals ii.) the ‘paracrine effect’ as mediated by mesenchymal stromal cells In i.) we use a large animal model of myocardial injury during the early postnatal develop-mental stage to establish …


Novel Roles For Classic And Predicted Cilia Genes, Melissa Bentley Jan 2021

Novel Roles For Classic And Predicted Cilia Genes, Melissa Bentley

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Primary cilia are highly conserved microtubule-based appendages that are present on the surface of nearly every mammalian cell type, and function as signaling hubs for the cell. Their function depends on their ability to assemble, traffic signaling components into and out of the cilium, and disassemble. These events require precise coordination of ciliary machinery and regulation of ciliary infrastructure including, but not limited to, the ciliary basal bodies, transition zone (TZ), and BBSome. The basal bodies reside at the base of the cilium and serve as the foundation for ciliary axoneme construction. Distal to the basal bodies is the TZ, …


Stress And Neuropeptide Y: Hippocampal Crossroads, Mariana Andrea Cortes Jan 2021

Stress And Neuropeptide Y: Hippocampal Crossroads, Mariana Andrea Cortes

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Anxiety disorders are the most common neuropsychiatric disorders diagnosed in adolescence and adulthood. While most animal models of trauma and stress-related disorders are performed in adults, and clinical trials for the treatment of these disorders typically include adult patients, there is a gap in knowledge for understanding how traumatic disorders develop in adolescence. Neuropeptide Y (NPY) is an endogenous peptide that provides anxiolytic benefits, and promotes feeding, arousal, and reduces inflammation. While being reduced in patients with depression and post-traumatic stress disorder (PTSD), animal models using NPY injections directly in to hippocampus have found it to be sufficient for blocking …


Hyperphosphatemia Contributes To Functional Iron Deficiency And Skeletal Muscle Wasting, Brian Anthony Czaya Jan 2021

Hyperphosphatemia Contributes To Functional Iron Deficiency And Skeletal Muscle Wasting, Brian Anthony Czaya

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Chronic kidney disease (CKD) is a global health threat that increases risk of death, which is credible to both impaired renal function and a multitude of CKD- associated comorbidities such as systemic inflammation, anemia and skeletal muscle dys- function. A distinctive feature of CKD is the dysregulation of mineral metabolism, where excess serum levels of phosphate (hyperphosphatemia) and of fibroblast growth factor 23 (FGF23) are not only viewed as biomarkers for disease severity but also exert deleterious effects towards various CKD-associated pathologies. Elevated levels of FGF23 can lead to the activation of FGF receptor 4 (FGFR4) in cell types that …


Targeting Oncogenic Microrna In Lung Cancer, Mackenzie Lauren Davenport Jan 2021

Targeting Oncogenic Microrna In Lung Cancer, Mackenzie Lauren Davenport

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Lung cancer is the leading cause of cancer-related death both in the United Statesand the world. While several genetic drivers of lung cancer have been identified, major improvements in patient outcome are lacking, highlighting the need to further understand the genetic and molecular mechanisms of this disease. The microRNA miR-31 has been implicated in oncogenesis in a variety of cancer types, and prior data from our laboratory has shown it to be overexpressed in human lung adenocarcinoma tumors compared to normal lung, high miR-31 levels correlate with decreased patient survival, and overexpression of miR-31 alone in the mouse lung epithelium …


Use-Dependent, Post-Critical Period Structural Plasticity In Primary Visual Cortex Following Central Vision Loss, Matthew Defenderfer Jan 2021

Use-Dependent, Post-Critical Period Structural Plasticity In Primary Visual Cortex Following Central Vision Loss, Matthew Defenderfer

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To facilitate learning throughout life, the adult brain must be capable of change, known as neuroplasticity. While evidence for adult structural plasticity in primary visual cortex (V1) exists, the relationship between plasticity and amount of use of a cortical region is not fully understood. Here, I use macular degeneration (MD) to model adult cortical plasticity. Macular degeneration causes loss of central vision, and patients learn to use a portion of peripheral vision called the preferred retinal locus (PRL) as a replacement for the fovea. The PRL is used more often than other usable areas of peripheral vision for daily tasks. …


The Hocl Response Of Escherichia Coli., Rhea Marie Derke Jan 2021

The Hocl Response Of Escherichia Coli., Rhea Marie Derke

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Inflammatory bowel diseases (IBDs), like Chron’s disease and ulcerative colitis, affect millions of people worldwide. There are limited treatment options available for these diseases because their direct causes are unknown. IBDs are characterized by chronic inflammation of the gastrointestinal tract and changes in the composition of the gut microbiome. Enterobacteria, including Escherichia coli, bloom to high levels in the gut during inflammation and contribute to the pathology of IBDs. E. coli must tolerate high levels of antimicrobial compounds produced by the immune system to survive during persistent inflammation. A large proportion of such compounds are reactive oxygen and reactive chlorine …


Identifying Novel Therapeutics And Therapeutic Entry Points For The Treatment Of Duchenne Muscular Dystrophy Through Regulation Of Gene Expression, Rylie Maria Hightower Jan 2021

Identifying Novel Therapeutics And Therapeutic Entry Points For The Treatment Of Duchenne Muscular Dystrophy Through Regulation Of Gene Expression, Rylie Maria Hightower

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My graduate research has primarily focused on genetic and epigenetic modifiers of Duchenne muscular dystrophy and understanding how those modifiers can be used as novel therapeutic entry points for treatment. A vast array of promising therapeutic strategies is being explored outside the realm of directly targeting dystrophin deficiency. This is primarily due to the lack of successful clinical trials that have demonstrated the ability to benefit a significant number of DMD patients. Here, I have expanded the field’s understanding of using the regulation of gene expression as a way to target dystrophin-deficiency associated pathology through, 1) therapeutic treatment of a …


Local Priming Of Long-Lived Tcf1+ Memory Cd8+ T Cell Responses In The Spleen During Influenza Virus Infection By Lung Derived Migratory Dendritic Cells, Meagan Jenkins Jan 2021

Local Priming Of Long-Lived Tcf1+ Memory Cd8+ T Cell Responses In The Spleen During Influenza Virus Infection By Lung Derived Migratory Dendritic Cells, Meagan Jenkins

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Initiation of CD8+ T cell responses to influenza virus infection requires the trafficking of activated lung-migratory dendritic cells (mDCs) from the lung into the lung-draining mediastinal LN (med-LN). As such, when mDCs are absent from the lungs or are unable to migrate into the med-LN, T cell responses are severely compromised, and the mortality rate increases in mouse models of influenza infection. Importantly, it is generally considered that mDCs die shortly after reaching the med-LN. Thus, the current paradigm suggests that priming of all subsets of influenza-specific CD8+ T cell responses by mDCs takes place solely in the med-LN. Recent …


Inducible T Cell Costimulator Stabilizes Regulatory T Cell Phenotype And Controls Host-Microbiota Interactions To Reduce Susceptibility To Intestinal Inflammation, Ashley Elizabeth Landuyt Jan 2021

Inducible T Cell Costimulator Stabilizes Regulatory T Cell Phenotype And Controls Host-Microbiota Interactions To Reduce Susceptibility To Intestinal Inflammation, Ashley Elizabeth Landuyt

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Genome wide association studies (GWAS) have identified a loss-of-function mutation in the gene encoding inducible T cell costimulator ligand (ICOSL) as correlating with inflammatory bowel disease (IBD). The reason for this association was largely unknown. ICOS signals have been implicated in controlling the dynamics of regulatory T (Treg) cells, which are essential to intestinal homeostasis. Compared to WT mice, ICOS-deficient mice possessed fewer Treg cells in the colonic lamina propria (cLP). The deficit in ICOS-deficient Treg cell numbers was attributable to preferential loss of Foxp3 expression. Bisulfite sequencing revealed that ICOS-deficient Treg cells did not demethylate conserved noncoding sequence 2 …


Mucus Matters: Mucociliary Physiology In Chronic Lung Diseases, Jacelyn Emily Peabody Lever Jan 2021

Mucus Matters: Mucociliary Physiology In Chronic Lung Diseases, Jacelyn Emily Peabody Lever

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The mucociliary escalator is an innate defense mechanism in the lung comprised of the ciliated, pseudostratified epithelium that lines the conducting airways and the mucus that sits atop the cilia. Mucus traps inhaled particulate matter/pathogens, and the cilia brush works in concert to propel the mucin gel proximally. Therefore, proper mucociliary physiology is critical to maintaining lung health. A metachronal wave propagated across the epithelium can occur when the phase of the ciliary stroke is shifted in time relative to its neighbors. Metachrony has been hypothesized to help overcome the viscoelastic forces required for the propulsion of mucus. Still, its …