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Articles 151 - 180 of 1029
Full-Text Articles in Medical Sciences
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 …
Restoring The Sphingolipid Balance In Glioblastoma, Cyntanna C. Hawkins
Restoring The Sphingolipid Balance In Glioblastoma, Cyntanna C. Hawkins
All ETDs from UAB
Glioblastoma (GBM) is a highly aggressive brain tumor with a median survival of 15 months even with standard of care—surgical resection, radiotherapy, and chemotherapy. Two of the key characteristics contributing to this malignancy are its highly invasive phenotype and resistance to the chemotherapy, temozolomide (TMZ). We, and others, have identified the sphingolipid balance as a driver of these phenotypes with dysregulated sphingolipid metabolism seen in GBM patient samples. The ceramidases, specifically acid ceramidase (ASAH1), mediate the balance between ceramides and sphingosine-1-phosphate (S1P). ASAH1 breaks down ceramides ultimately forming S1P. While ceramides induce cell death, S1P promotes migration and cell survival. …
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 …
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
of ALL survivors are at risk for reduced functional outcomes, and these outcomes may be more strongly related to executive functioning than neighborhood-specific variables or IEP support. Long-term goals include translating findings into practice to remediate adaptive or academic difficulties in ALL survivors.
Il-22 Mediated Host Defense During Attaching-Effacing Pathogen Infection, Baiyi Cai
Il-22 Mediated Host Defense During Attaching-Effacing Pathogen Infection, Baiyi Cai
All ETDs from UAB
Intestinal infections are a cause of morbidity and mortality worldwide and remain a public threat. Interleukin (IL)-22 is central to host immune responses in the intestine during infection and inflammation. IL-22 can be produced by both innate and adaptive immune cells, yet their relative contributions to host protection remain unclear. Here we demonstrated the specific role and mechanism for IL-22 from innate and adaptive sources to protect the host. Using the Citrobacter rodentium (C.r) model, we found that IL-22 from innate cell, protect the host during early infection. IL-22 induces epithelial production of polymorphonuclear neutrophils (PMN) recruiting chemokine CXCL1, CXCL2 …
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 …
Characterizing The Role Of Necroptosis Of Airway Epithelial Cells In The Immune Response To Respiratory Pathogens, Ashleigh Nichole Riegler
Characterizing The Role Of Necroptosis Of Airway Epithelial Cells In The Immune Response To Respiratory Pathogens, Ashleigh Nichole Riegler
All ETDs from UAB
Necroptosis, a programmed form of lytic cell death, is initiated by various viral and bacterial pathogens through irreparable ion dysregulation and energy depletion. This cellular damage results in the activation of the cellular kinases RIPK1 and RIPK3, consecutively, and the activation and membrane targeting of MLKL, the latter responsible for lysis. Here we have demonstrated that necroptosis of airway epithelial cells is key in the development of the adaptive immune response to asymptomatic colonization by Streptococcus pneumoniae (Spn). Briefly, necroptotic deficient animals or wildtype animals colonized with Spn lacking the necroptosis-triggering pneumolysin toxin, failed to recruit CD11c+ leukocytes to the …
Cns Antigen Presentation And Immune Cell Infiltration In An Α-Syn Model Of Parkinson Disease, Aubrey Michelle Schonhoff
Cns Antigen Presentation And Immune Cell Infiltration In An Α-Syn Model Of Parkinson Disease, Aubrey Michelle Schonhoff
All ETDs from UAB
Parkinson disease (PD) is a neurodegenerative movement disorder that is characterized by aggregated alpha-synuclein (a-syn), loss of dopaminergic neurons, and neuroinflammation. This neuroinflammation includes the activation of immune cells that reside in the CNS, such as microglia and border associated macrophages (BAMs), in addition to the infiltration of peripheral leukocytes and increased cytokine and chemokine production. Because of the involvement of both the innate and adaptive immune systems, we sought to investigate their interaction through antigen presentation and determine what role this played in disease progression. Using an a-syn based mouse model of PD, our studies have provided evidence via …
Assesing The Degree Of Intereron Gamma Induced Stat1 Activation On Peripheral Lymphocytes In Patietns With Rheumatoid Arthritis, Vishal Sharma
Assesing The Degree Of Intereron Gamma Induced Stat1 Activation On Peripheral Lymphocytes In Patietns With Rheumatoid Arthritis, Vishal Sharma
All ETDs from UAB
Rheumatoid Arthritis (RA) is a systemic autoimmune disease with debilitating side effects, from joint swelling to bone erosion and bone deformation. Geographically, RA affect 0.5 – 1% of the worldwide populations, affecting women more than men. Studies have shown that CD4 T cells infiltrate RA synovium and are key to the pathogenesis of RA. Furthermore, drugs targeting co-stimulatory T cell molecules such as abatacept can be beneficial in controlling RA disease activity.Interferon gamma (IFN) is a pleotropic cytokine that contributes to inflammation by aiding in CD4 T cell differentiation into Th1 subtype, enhancing MHC class II presentation, supplementing lymphocyte trafficking, …
Mechanism Of Stat3 Mediated Drug Persistence In Chronic Myeloid Leukemia Stem Cells, Sweta B. Patel
Mechanism Of Stat3 Mediated Drug Persistence In Chronic Myeloid Leukemia Stem Cells, Sweta B. Patel
All ETDs from UAB
Drug persistence is one of the major impediments for cancer therapeutics. There are two known evolutionary models for tumor drug persistence. First, a pre-existing sub-population is inherently resistant to treatment; and second, a sub-population acquires resistance by drug-induced molecular reprograming. One ideal model to study the mechanism of drug persistence is chronic myeloid leukemia (CML), a hematopoietic stem cell (HSC) disorder. HSCs acquire a single translocation between chromosome 9 and 22, forming BCR-ABL, a constitutively active tyrosine kinase. Tyrosine kinase inhibitors (TKI), the standard regimen, have been able to efficaciously control CML and yet many patients relapse upon treatment discontinuation …
The Psychological, Social, And Bioinformatic Considerations For The Return Of Continental Genetic Ancestry Estimates And Other Secondary Sequencing Results, Jaimie Leighan Richards
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 …
Biomarker And Target Discovery In Cancer, Alyncia Dominique Robinson
Biomarker And Target Discovery In Cancer, Alyncia Dominique Robinson
All ETDs from UAB
Cancer is a complex disease characterized by uncontrolled growth of transformed cells that can arise in many tissue types throughout the body (e.g., breast, lung, prostate, pancreas, lymph nodes) and is a major cause of death worldwide. Cancer progression resulting in aggressive or metastatic disease accounts for one of the leading causes of death worldwide, second only to heart disease in the US. Incidentally, cancer-related mortality has been on a steady decline, dropping 25% over the last 25 years [1]. This could be attributed to improved and earlier diagnoses and better treatment options being developed over the past few decades. …
Suppressing Islet Graft Rejection With Antioxidant-Based Encapsulation Materials, Jessie Marie Barra
Suppressing Islet Graft Rejection With Antioxidant-Based Encapsulation Materials, Jessie Marie Barra
All ETDs from UAB
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 …
Neonatal Murine Cytomegalovirus Infection Disrupts Synapse Remodeling During Development, Jerome Moulden
Neonatal Murine Cytomegalovirus Infection Disrupts Synapse Remodeling During Development, Jerome Moulden
All ETDs from UAB
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 …
Studies On Nontypeable Haemophilus Influenzae Biofilm Persistence & Redox Homeostasis In Chronic Bacterial Diseases, Benjamin C. Hunt
Studies On Nontypeable Haemophilus Influenzae Biofilm Persistence & Redox Homeostasis In Chronic Bacterial Diseases, Benjamin C. Hunt
All ETDs from UAB
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
Diurnal Variation In Hippocampal Neurophysiology And Pathophysiology, Allison R. Fusilier
All ETDs from UAB
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
Tau-Sh3 Interactions And Alzheimer's Disease, Jonathan Roth
All ETDs from UAB
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 …
Effeccts Of Hiv-1 Tat On Tspo, A Biomarker Of Neuroinflammation, Nguyen Thuy Nhu Nguyen
Effeccts Of Hiv-1 Tat On Tspo, A Biomarker Of Neuroinflammation, Nguyen Thuy Nhu Nguyen
All ETDs from UAB
HIV-associated neurocognitive disorders (HAND) produces serious neurological dysfunction for > 50% of people living with HIV (PLWH). As antiretroviral therapy (ART) has transformed HIV into a chronic disease, and since most ART does not effectively cross the blood brain barrier, HAND is predicted to further increase in prevalence in PLWH. The HIV-Trans-Activator of Transcription (Tat) is known to persist in the central nervous system (CNS) of chronically infected HIV+ individuals. In several preclinical studies, HIV-Tat has been shown to be neurotoxic and important for HIV pathogenesis. Translocator protein (TSPO), an 18 kDa mitochondrial protein, has been shown to be increased via …
Characterization Of Rna Polymerase I Trigger Loop Mutations, Collin Ainslie
Characterization Of Rna Polymerase I Trigger Loop Mutations, Collin Ainslie
All ETDs from UAB
RNA polymerases are primarily multi-subunit enzymes that synthesize RNAs from template DNA strands. RNA polymerase I (Pol I) is the eukaryotic RNA polymerase that synthesizes the majority of ribosomal RNA (rRNA) for ribosome production. These include the 5.8S, 28S, and 18S rRNAs which are synthesized from a polycistronic gene in the nucleolus. The rRNAs synthesized by Pol I, the 5S rRNA, & ribosomal proteins come together to synthesize ribosomes through ribosome biogenesis. Dysregulation of Pol I activity has been established to contribute to dysregulation of ribosome biogenesis and disease state development. These conditions include but are not limited to Cincinnati …
Characterization Of Cellular And Viral Factors That Define The Stability Of The Latent Hiv-1 Reservoir, Eric Carlin
Characterization Of Cellular And Viral Factors That Define The Stability Of The Latent Hiv-1 Reservoir, Eric Carlin
All ETDs from UAB
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 …
Tgfβ Provides The Backbone Of Embryogenesis: Elucidating The Role Of Tgfβ Signaling And Its Downstream Effectors On Spinal Column Development, Sade Williams Clayton
Tgfβ Provides The Backbone Of Embryogenesis: Elucidating The Role Of Tgfβ Signaling And Its Downstream Effectors On Spinal Column Development, Sade Williams Clayton
All ETDs from UAB
The spinal column is composed of two components, the vertebra (VB) that provide support and the intervertebral disc (IVD) that provide weight distribution. The structural integrity of IVDs is maintained by a fibrocartilaginous tissue called the annulus fibrosus (AF) which can degenerate with age or trauma and contribute to chronic back pain. There are currently no diseases modifying treatments that curb IVD degeneration. Regenerative therapies to treat IVD degeneration can be developed from identifying the signaling factors required for AF differentiation, but these factors are unknown. Previously, we showed that TGFβ signaling is required for AF formation in mice and …
Production And Purification Of Titanium-45 For Imaging Of Psma+ Prostate Cancer, Ivis Francis Chaple
Production And Purification Of Titanium-45 For Imaging Of Psma+ Prostate Cancer, Ivis Francis Chaple
All ETDs from UAB
Positron Emission Tomography (PET) has revolutionized the world of molecular imaging, increasing the potential for improved diagnosis and characterization of various disease states, including cancer. Molecular biology has afforded the knowledge that each type of cancer cell is different, and these differences can be leveraged to develop methods for targeting these cells for imaging or therapy, as well as understanding of other characteristics. Due to the increased diversity in available targets, there has been an equal need to develop new agents used to image these receptors. Radioisotopes with varying halflives, chemical and nuclear properties have been studied in recent years …
Transcriptional Regulation And Islet Transplantation Advantages Of Brown Adipose Tissue, Jessica D. Kepple
Transcriptional Regulation And Islet Transplantation Advantages Of Brown Adipose Tissue, Jessica D. Kepple
All ETDs from UAB
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 …
Glycolytic Myeloid Cells Protect The Host In Tuberculosis, Hayden Thomas Pacl
Glycolytic Myeloid Cells Protect The Host In Tuberculosis, Hayden Thomas Pacl
All ETDs from UAB
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 …
Combining Meg And Fmri To Examine Dynamic Task-Related Brain Activity With High Spatio-Temporal Resolution, Sangeeta Nair
Combining Meg And Fmri To Examine Dynamic Task-Related Brain Activity With High Spatio-Temporal Resolution, Sangeeta Nair
All ETDs from UAB
The characterization of brain networks contributing to healthy learning and memory can inform abnormalities and treatment approaches among clinical populations. A recent shift from lesion-based to network-based approaches of studying healthy and atypical brain development highlights the need for a more comprehensive understanding across spatiotemporal domains, particularly in the case of high-level cognitive processes. Both, associative learning and working memory involve distributed and interconnected networks of specialized brain regions. Dynamic communication within- and betweensuch systems are unable to be fully resolved by individual non-invasive imaging techniques such as fMRI or MEG. While fMRI serves as an ideal tool to investigate …
Analysing The Contribution Of Snare-Dependent Exocytosis From Astrocytes To Huntinton's Disease Pathogenesis Using The Bachd Mouse Model, Annesha C. King
Analysing The Contribution Of Snare-Dependent Exocytosis From Astrocytes To Huntinton's Disease Pathogenesis Using The Bachd Mouse Model, Annesha C. King
All ETDs from UAB
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 …
A Role For Inf-Ɣ-Inducble Transcription Factors In Antibody Secreting Cell Differentiation, Jessica N. Peel
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 …