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Articles 1 - 30 of 52
Full-Text Articles in Medicine and Health Sciences
St6gal-I Mediated Sialylation Promotes Pancreatic Ductal Adenocarcinoma Progression And Chemoresistance, Asmi Chakraborty
St6gal-I Mediated Sialylation Promotes Pancreatic Ductal Adenocarcinoma Progression And Chemoresistance, Asmi Chakraborty
All ETDs from UAB
ST6Gal-I adds α2-6 sialic acids to select N-glycosylated cell surface receptors, thereby modulating receptor function and intracellular signaling. ST6Gal-I is upregulated in various carcinomas and confers cancer stem cell (CSC) properties evidenced by tumorspheroid growth, chemoresistance and tumor initiating potential. In pancreatic ductal adenocarcinoma (PDAC), ST6Gal-I conferred gemcitabine resistance by abrogating DNA damage and altering expression levels of gemcitabine metabolism genes. Further, ST6Gal-I promoted resistance to chronic gemcitabine treatment. Additionally, metastatic clones of a PDAC cell line had increased ST6Gal-I expression and ST6Gal-I knockdown enhanced gemcitabine sensitivity. To investigate the physiological consequences of ST6Gal-I in PDAC, murine models were used. …
Determination Of The Role Of Smu_833 In The Fitness And Virulence Of Cariogenic Streptococcus Mutans, Katherine Lynn Rainey
Determination Of The Role Of Smu_833 In The Fitness And Virulence Of Cariogenic Streptococcus Mutans, Katherine Lynn Rainey
All ETDs from UAB
Dental caries, commonly known as tooth decay, is the most common infectious disease worldwide. The main etiological agent of dental caries is Streptococcus mutans which can readily form a biofilm on the surface of teeth and produce acids through the metabolism of dietary sugars, which is largely responsible for the demineralization and subsequent destruction of tooth enamel. In addition, S. mutans synthesizes extracellular glucosyltransferases (Gtfs) capable of breaking apart dietary sucrose and polymerizing the glucose subunits into the sticky glucan matrix of the biofilm, imperative for the formation of robust, three-dimensional biofilms. Currently used caries therapies are not species-specific and …
Intracellular Compartment-Specific Abnormalities In Proteasome Expression And Activity In The Superior Temporal Gyrus In Schizophrenia, Madeline R. Scott
Intracellular Compartment-Specific Abnormalities In Proteasome Expression And Activity In The Superior Temporal Gyrus In Schizophrenia, Madeline R. Scott
All ETDs from UAB
Protein homeostasis is an emerging component of schizophrenia (SZ) pathophysiology. Proteomic alterations in SZ are well-documented; however the underlying mechanism driving these changes remains unknown. The ubiquitin proteasome system (UPS) is fundamental to protein homeostasis regulation, and UPS transcript abnormalities in both blood and brain have been observed in SZ. Supporting a role for UPS dysfunction in SZ, we have reported decreased protein expression of ubiquitin-associated proteins in SZ brain. However, previous work on the proteasome has been limited to transcript expression. In the following studies we sought to address this gap in knowledge by characterizing proteasome dysfunction in the …
Acetylcholine Signaling In Glioblastoma Invasion And Peritumoral Hyperexcitability, Emily Grace Thompson
Acetylcholine Signaling In Glioblastoma Invasion And Peritumoral Hyperexcitability, Emily Grace Thompson
All ETDs from UAB
Glioblastomas are the most common and deadly form of primary brain cancer in adults. Current treatment strategies are aggressive, including a combination of surgical resection, radiotherapy, and chemotherapy. However, median patient survival has remained stagnant at 12 to 15 months for the last several decades. This dismal patient outcome has prompted efforts to understand the unique characteristics of these tumors, since traditional therapeutics have not been efficacious. Extensive invasion is a salient feature of glioblastomas that significantly diminishes the effectiveness of current treatment strategies and is ultimately the cause of tumor recurrence within 2 years in approximately 80% of patients. …
Endothelial N-Glycan Hypoglycosylation Enhances Cd16+ Monocyte Adhesion: A Role For Alpha-Mannosidases, Kellie Regal Mcdonald
Endothelial N-Glycan Hypoglycosylation Enhances Cd16+ Monocyte Adhesion: A Role For Alpha-Mannosidases, Kellie Regal Mcdonald
All ETDs from UAB
Monocyte extravasation through the endothelial layer is a hallmark of atherosclerotic plaque development and is mediated by heavily glycosylated surface adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1). Human monocytes have been classified into three distinct groups: classical (anti-inflammatory; CD14+/CD16-), nonclassical (patrolling; CD14+/CD16++), and intermediate (pro-inflammatory; CD14++/CD16+). The CD16+ nonclassical / intermediate monocytes have been implicated in atherosclerosis progression and their levels positively associate with adverse cardiac events. However, there is a relative lack of understanding as to whether there are distinct mechanisms that regulate CD16+ vs. CD16- monocyte adhesion to the inflamed endothelium. Our previous data identified a high-mannose …
Characterization Of Chemical Uptake And Aryl Hydrocarbon Receptor Mutations In Zebrafish, Jaclyn Paige Souder
Characterization Of Chemical Uptake And Aryl Hydrocarbon Receptor Mutations In Zebrafish, Jaclyn Paige Souder
All ETDs from UAB
In a society driven by technology and industry, we must be increasingly aware of how changes to our environment impact our health. This is especially true concerning embryonic development, which is easily influenced by extra-embryonic factors, including environmental contaminants. Determining how exogenous compounds are absorbed, which receptors they act through, and how these receptors act endogenously is important to fully understand to what extent developmental exposures impact fetal and adult health. I have used the zebrafish model system to address these questions for two classes of environmentally-relevant chemicals—estrogens and dioxins. First, I developed an assay to measure the uptake of …
Marcks Effector Domain: Functions In Glioblastoma Progression And Novel Cytolytic Therapy, Nicholas James Eustace
Marcks Effector Domain: Functions In Glioblastoma Progression And Novel Cytolytic Therapy, Nicholas James Eustace
All ETDs from UAB
Glioblastoma (GBM; grade IV astrocytoma) is the most common primary adult brain malignancy and remains incurable despite tremendous advances in our understanding of this heterogeneous disease. In this dissertation, we explore the challenges encountered in the treatment of GBM and discuss a promising new therapeutic approach gleaned from studies of the phospholipid binding “effector” domain (ED) of the protein Myristoylated alanine-rich protein C kinase substrate (MARCKS). Following an introduction to central nervous system (CNS) tumors and the grading of diffuse gliomas, we explain how recent advancements to our understanding of the cellular and molecular composition of CNS tu-mors, and the …
Bet Bromodomain Inhibition As An Approach For Treatment Of Cholangiocarcinoma, Samuel Charles Fehling
Bet Bromodomain Inhibition As An Approach For Treatment Of Cholangiocarcinoma, Samuel Charles Fehling
All ETDs from UAB
Cholangiocarcinoma (CCA) is a highly aggressive neoplasm which arises from the epithelial layer of the biliary tract. It is the second most common primary hepatic malignancy. As CCA is typically diagnosed at late disease stage, the current standard of care, resection followed by gemcitabine with cisplatin, is not effective. Further, up to 90% of CCA patients are ineligible for resection. Of those eligible for resection, postoperative chemotherapy does not prolong overall survival leading to a 5-year survival of ~30%. Previously, mutations have been identified in KRAS (17% of CCA cases), TP53 (44%) and SMAD4 (17%) but none have been recognized …
Identification Of Two Spop-Mediated Pathways In Prostate Cancer Progression, Joshua Fried
Identification Of Two Spop-Mediated Pathways In Prostate Cancer Progression, Joshua Fried
All ETDs from UAB
Prostate cancer is one of the most common malignancies and causes of cancer related death in men. Morbidity is primarily attributed to late-stage and metastatic disease. Re-cent genomic screening studies have revealed that the Speckle type Poz Protein (SPOP) is the most frequently altered gene by missense mutations in prostate cancer. Interestingly, all of the identified mutations were located in the substrate binding domain of SPOP. Here, two pathways highlighting the impact of SPOP mutation on prostate cancer are pre-sented. First, evidence showing that one of the naturally occurring SPOP mutations, ser-ine 119 to asparagine (S119N), induces radiosensitivity and an …
Baf Chromatin Landscaping During Bone Formation And Maintenance, Tanner Cole Godfrey
Baf Chromatin Landscaping During Bone Formation And Maintenance, Tanner Cole Godfrey
All ETDs from UAB
Bone loss is a worldwide problem resulting in increased risk of fracture. Osteoblasts are responsible for bone synthesis; therefore, treatments promoting osteoblast differentiation and/or activity would result in increased bone formation. The regulation of DNA accessibility is a key mechanism controlling gene expression and cellular differentiation. BAF (BRG1 Associated Factor) mediated chromatin remodeling increases DNA accessibility by sliding or ejecting nucleosomes. This process can occur in a cell type specific manner based on the composition of BAF. In many tissue types, a unique combination of BAF subunits has been identified to be responsible for the maintenance or differentiation of that …
Structural Studies Of Some Proteins Responsible For Bacterial Pathogenesis, Kartik Manne
Structural Studies Of Some Proteins Responsible For Bacterial Pathogenesis, Kartik Manne
All ETDs from UAB
A wide range of infections is attributed to the pathogenesis of Gram-positive bacteria. The emergence of multi-drug-resistant Gram-positive pathogens has been a significant health concern and present serious therapeutic challenges globally. Some of the common Gram-positive bacterial species like Streptococcus pneumonia, Group B Streptococcus, and Staphylococcus aureus are infectious by employing several virulence factors for initial adhesion, colonization, biofilm initiation and dispersion, complement evasion, nutrient acquisition, and infection. The structural insights into these virulence factors are essential for understanding their mode of action, and also for developing a new class of antibiotics; a significant interest of many researchers. Pneumococcal adhesive …
Appropriately Timed Epigenetic Manipulation With Histone Deacetylase Inhibitors As A Platform Approach To Tumor Immunotherapy, Tyler Mccaw
All ETDs from UAB
In contrast to chemotherapy and radiotherapy, immunotherapy is able to respond in proportion to tumor burden and continue to evolve in parallel with the tumor mass and metastatic sites. In this way, immune-based cancer therapies are a living drug and hold enormous potential. In this work, we enforce expression of MHCII on a murine breast cancer model to study how changes in tumor biology can drive improved T cell-mediated responses. We next use histone deacetylase inhibitors to manipulate the microenvironment through a more clinically relevant, therapeutic approach. Herein, improvements in tumor control were driven by CD8 T cells and IFNγ, …
Ribosomal Rna Synthesis Is Regulated By Pathways That Respond To Environmental And Stress Conditions, Saman Najmi
Ribosomal Rna Synthesis Is Regulated By Pathways That Respond To Environmental And Stress Conditions, Saman Najmi
All ETDs from UAB
Ribosome biogenesis is one of the most central processes to cellular growth and metabolism. The synthesis of ribosomal RNA (rRNA) by RNA polymerase I (Pol I) is thought to be rate limiting for ribosome biogenesis, and is therefore subject to extensive regulation. The work presented in this dissertation characterizes two previously undiscovered pathways regulating rRNA synthesis. Due to the direct connection between ribosome biogenesis (and rRNA synthesis) and cellular proliferative potential, Pol I activity is upregulated in cancers. Cancer cells are hypersensitive to inhibition of Pol I, a quality that makes Pol I an attractive target for anticancer therapeutics. The …
Early Life Stress And Immune Responses In Adult Rat Kidneys, Ijeoma E. Obi
Early Life Stress And Immune Responses In Adult Rat Kidneys, Ijeoma E. Obi
All ETDs from UAB
Globally, human studies show overwhelming associations between adverse childhood experiences and cardiovascular disease (CVD) and CVD risks throughout adult life. As early as 6 years old, there are significant associations between childhood adversity and inflammation, and those association are observed throughout adult life as well. Over a decade ago, rodent models were used to establish the importance of the immune cells in hypertension, which is the major risk factor in developing CVD. Although these associations in humans are important, they pose several limitations that can be overcome by the use of animal models to study the molecular mechanisms that are …
Mechanisms Of Acute Kidney Injury: The Role Of Ferritin Heavy Chain In Renal Heme-Unology, Laurence Marie Black
Mechanisms Of Acute Kidney Injury: The Role Of Ferritin Heavy Chain In Renal Heme-Unology, Laurence Marie Black
All ETDs from UAB
The kidneys are complex, multi-faceted organs that are responsible for regulatory processes, such as fluid homeostasis, hormone production, blood pressure regulation, and systemic toxin removal. Sudden disruption of these processes by acute kidney injury (AKI) causes rapid decline in renal function as well as significant morbidity and mortality. AKI is a significant clinical concern, affecting up to 13.3 million people globally each year and has the propensity to progress to chronic kidney disease (CKD), though the mechanism remains undefined. One reason for this is due to the lack of understanding of models used to study both AKI and CKD, hindering …
Mechanisms Of Acute Kidney Injury: The Role Of Ferritin Heavy Chain In Renal Heme-Unology, Laurence Marie Black
Mechanisms Of Acute Kidney Injury: The Role Of Ferritin Heavy Chain In Renal Heme-Unology, Laurence Marie Black
All ETDs from UAB
The kidneys are complex, multi-faceted organs that are responsible for regulatory processes, such as fluid homeostasis, hormone production, blood pressure regulation, and systemic toxin removal. Sudden disruption of these processes by acute kidney injury (AKI) causes rapid decline in renal function as well as significant morbidity and mortality. AKI is a significant clinical concern, affecting up to 13.3 million people globally each year and has the propensity to progress to chronic kidney disease (CKD), though the mechanism remains undefined. One reason for this is due to the lack of understanding of models used to study both AKI and CKD, hindering …
The Role Of Nudc In Rod Photoreceptor Cell Maintenance: A New Function For An Old Protein, Evan Boitet
The Role Of Nudc In Rod Photoreceptor Cell Maintenance: A New Function For An Old Protein, Evan Boitet
All ETDs from UAB
The overall health and maintenance of rod photoreceptors depends on directed vectorial transport of rhodopsin from its synthesis within the inner segment to its target destination the outer segment disk membranes. Numerous proteins are known to be involved in molecular interactions with rhodopsin during transport, including the interaction of nuclear distribution protein C (nudC) with rhodopsin that was first described in Xenopus laevis. We found that the interaction of nudC and rhodopsin is conserved in mammalian retina. This interaction is direct and aberrant expression of nudC results in subcellular localization of rhodopsin. We show for the first time that nudC …
The Impact Of Redox Stress In Primary Hyperoxaluria Type 1, Brianna Buchalski
The Impact Of Redox Stress In Primary Hyperoxaluria Type 1, Brianna Buchalski
All ETDs from UAB
Primary Hyperoxaluria (PH) is a family of three inborn errors of glyoxylate metabolism resulting in endogenous oxalate overproduction. PH1 is the most common and most severe form of the disorder when compared to PH2 and PH3. PH1 can result in systemic oxalosis or end stage renal disease, and there is currently no cure for this disorder. The only curative treatment is combined liver/kidney transplant. The difficulty in defining a cure for the disorder arises from poor knowledge of the sources of endogenous oxalate and a lack of understanding in the underlying pathophysiology of the disorder. For these reasons, we have …
Receptor Sialylation By St6gal-I Promotes Tumor Progression By Enhancing Tumor Cell Survival And Epithelial To Mesenchymal Transition, Colleen Maeve Britain
Receptor Sialylation By St6gal-I Promotes Tumor Progression By Enhancing Tumor Cell Survival And Epithelial To Mesenchymal Transition, Colleen Maeve Britain
All ETDs from UAB
The upregulation of a certain subset of glycosyltransferases was an early marker for cancer development. Specifically, ST6Gal-I, which adds an α2-6 linked sialic acid to N-glycans on proteins bound for the plasma membrane or secretion, is selectively upregulated upon malignant transformation. Our laboratory has shown that ST6Gal-I is implicated in many facets of tumor biology and is an important mediator of tumorigenesis. For example, ST6Gal-I activity promotes the survival of cells when challenged with hypoxia, FasL, or TNFα, confers resistance to chemotherapeutics, enhances tumor cell migration and invasion, and fosters a cancer stem cell phenotype. The work presented in this …
Characterizing The Hiv-1 Envelope N-Glycan Shield, Audra Ann Hargett
Characterizing The Hiv-1 Envelope N-Glycan Shield, Audra Ann Hargett
All ETDs from UAB
In 2017, there was an estimated 1.8 million new HIV-1 infections worldwide. Development of an effective HIV-1 vaccine would begin to quell this global pandemic. HIV-1 envelope (Env) glycoprotein is the main vaccine candidate target due to the immune systems ability to generate broadly neutralizing antibodies (bnAbs) against Env. Approximately 90 N-glycans form a glycan shield that is the primary interface between the virus and host immune system. Key glycan motifs within the glycan shield are targets for bnAbs and are necessary for HIV-1 infectivity. Herein, we explore how naturally occurring mutations alter the glycan shield and HIV-1 Env function. …
Investigating The Rho-Kinase (Rock) Signaling Pathway As A Therapeutic Target In Alzheimer’S Disease, Benjamin Wade Henderson
Investigating The Rho-Kinase (Rock) Signaling Pathway As A Therapeutic Target In Alzheimer’S Disease, Benjamin Wade Henderson
All ETDs from UAB
Current estimates project that there are approximately 5.4 million Americans affected by Alzheimer’s disease (AD). While this number is expected to dramatically increase in the years to come, there is currently no disease modifying therapeutic to prevent or slow AD progression. Cognitive decline is a clinical hallmark of AD, while accumulation of amyloid-β (Aβ) is a pathological hallmark. Work in the field has demonstrated that mitigating Aβ levels may serve as a rational therapeutic avenue to slow progression of the disease. Pharmacologic inhibition of the Rho-associated protein kinases (ROCK1 and ROCK2) is proposed to curb Aβ levels, and mechanisms that …
Bk Polyomavirus Activates The Dna Damage Response To Hijack Host Cell Cycle Control, Joshua L. Justice
Bk Polyomavirus Activates The Dna Damage Response To Hijack Host Cell Cycle Control, Joshua L. Justice
All ETDs from UAB
BK Polyomavirus (BKPyV) is a DNA tumor virus that latently infects the >90% of humanity. BKPyV infection is inconsequential in healthy individuals; however, the immunocompromised carry increased risk of viral reactivation that can lead to a number of genitourinary diseases. Overall, BKPyV reactivation is a major risk factor for kidney dysfunction and failure following solid organ transplantation. There are no approved therapeutics to treat BKPyV infection, therefore studies have focused on understanding the host/virus interactions that drive infection to identify therapeutic targets. The PyV genome is small and does not encode a polymerase. Cellular transformation by the viral oncogene, T …
The Electronic Health Record And The Clinical Informatics Researcher: A Journey To Predicting False Positive Alerts With Patient Characteristics, Timothy Kennell
The Electronic Health Record And The Clinical Informatics Researcher: A Journey To Predicting False Positive Alerts With Patient Characteristics, Timothy Kennell
All ETDs from UAB
Since their introduction in the 1960s, electronic medical systems have brought with them tremendous opportunities and difficult challenges. In order to address patient safety, Clinical Decision Support (CDS) was added to the system, many times in the form of "pop-up" alerts. However, traditional alert typically do not incorporate enough patient-specific context resulting in inaccurate warnings. In response, clinicians override many of them. However, the high exposure to false positive alerts results in alert fatigue, a desensitization to future ones. This issue decreases patient safety by causing clinicians to ignore legitimate alerts. Despite some shortcomings, the data in modern Electronic Health …
Structural And Functional Insights Into The Influenza A Virus Non-Structural Protein 1 Effector Domain, Alex Kleinpeter
Structural And Functional Insights Into The Influenza A Virus Non-Structural Protein 1 Effector Domain, Alex Kleinpeter
All ETDs from UAB
The influenza A virus (IAV) non-structural protein 1 (NS1) is a highly multifunctional viral protein responsible for antagonizing the type-I interferon (IFN) response to infection. NS1 has therefore been identified as a potentially effective target for the development of novel anti-influenza compounds. Furthermore, it is important to understand the molecular underpinnings driving NS1 function to more effectively elucidate antiviral targets. In this dissertation, we have contributed significant insight into NS1’s potential as an antiviral target, and the structure-function relationships driving its activity in an infected cell. First, we structurally characterized the binding of two known influenza inhibitors (A9 and A22) …
A Structure Based Approach For Defining Ligand Interaction Requirements With Atp-Binding Cassette Proteins, Christina A. Le
A Structure Based Approach For Defining Ligand Interaction Requirements With Atp-Binding Cassette Proteins, Christina A. Le
All ETDs from UAB
Membrane proteins belonging to the ATP-Binding Cassette (ABC) superfamily are responsible for transporting substrates into or out of cells. ABC transporters, such as P-glycoprotein (Pgp/ABCB1) defend cells by the active efflux of many chemically diverse cytotoxic compounds. The ABC protein, CFTR/ABCC7, is a passive chloride ion channel that provides fluid homeostasis. Pgp and CFTR of are high clinical interest since mutations in CFTR can result in Cystic Fibrosis (CF) and upregulation of Pgp in tumor cells can result in multidrug resistance (MDR). There has been a major effort to develop clinical drugs to treat CF by either repairing defects in …
Kidney Resident Macrophages Utilize Developmental Programming During Healing From Acute Kidney Injury, Jeremie Matthew Peabody Lever
Kidney Resident Macrophages Utilize Developmental Programming During Healing From Acute Kidney Injury, Jeremie Matthew Peabody Lever
All ETDs from UAB
Acute kidney injury (AKI) can be a devastating condition, affecting up to sixty percent of critically ill patients in the United States. Despite the fact that AKI is associated with an increased risk of chronic kidney disease (CKD) and mortality, there are no targeted therapies available to treat it. Kidney resident macrophages (KRM) are likely necessary for healing and resolution of animal models of AKI. However, there remains a gap in knowledge regarding how KRM effect this function. The purpose of my thesis was to elucidate lineage relationships and functionally relevant adaptations of KRM and monocyte-derived mononuclear phagocytes (infiltrative MP) …
Bdnf/Trkb.T1 Signaling: A Novel Mechanism Of Astrocyte Morphological Maturation, Leanne Holt
Bdnf/Trkb.T1 Signaling: A Novel Mechanism Of Astrocyte Morphological Maturation, Leanne Holt
All ETDs from UAB
Astrocytic morphogenesis and maturation are critical steps in central nervous system (CNS) development. During morphological maturation, astrocytes extend fine peripheral processes which infiltrate the neuropil and form intimate partners with neuronal structures, including synapses, where they facilitate neurotransmitter and K+ uptake and contribute to synaptic development and stabilization. The developmental time window of astrocyte morphological maturation and refinement is well defined, but the molecular mechanisms that underlie this process are not understood. Brain derived neurotrophic factor (BDNF) is a critical growth factor involved in the development and maturation of neurons. We developed a novel technique for the specific isolation of …
Characterization Of The Tgfb Pathway And Its Role In Prostaglandin Metabolism In C. Elegans, Muhan Hu
Characterization Of The Tgfb Pathway And Its Role In Prostaglandin Metabolism In C. Elegans, Muhan Hu
All ETDs from UAB
Cell to cell communication is fundamental to all life processes, from fertilization to death. The TGFß superfamily is a large family of proteins that is involved in a wide array of physiological and pathological processes, including development, wound healing, immune system function, cancer, and reproduction. This group of signaling peptides is well conserved across many organisms, from basic nematode to humans. While many studies have aimed to delineate the functions of TGFß, they have also unveiled the complexity of this multifunctional family of ligands. In this thesis, I take advantage of the simple C. elegans model system to study the …
The Role Of The St6gal-I Sialyltrasferase In Protecting Tumor Cells From Hypoxic Stress, Robert Brent Jones
The Role Of The St6gal-I Sialyltrasferase In Protecting Tumor Cells From Hypoxic Stress, Robert Brent Jones
All ETDs from UAB
An emerging concept in cancer biology is that surface glycosylation can play important roles in the regulation of cancer development and progression. Our group and others have shown that ST6Gal-I, a sialyltransferase that adds α2-6-linked sialic acids to N-glycosylated proteins, is upregulated in many cancers. Furthermore, data has indicated that ST6Gal-I acts as a pro-survival factor in a variety of settings, including resistance to chemotherapeutic drugs, radiotherapy resistance, and serum deprivation. The work presented in this dissertation adds to this understanding of ST6Gal-I’s role as a potent pro-survival factor and explores ST6Gal-I’s function in aiding tumor cells to survive hypoxic …
Structural And Functional Insights Into Influenza A Virus Ns1-Mediated Rig-I Antagonism, Alexander Jureka
Structural And Functional Insights Into Influenza A Virus Ns1-Mediated Rig-I Antagonism, Alexander Jureka
All ETDs from UAB
The influenza virus non-structural protein 1 is well known to antagonize the host innate immune response through its interaction with the innate immune sensor, retinoic acid induc-ible gene I (RIG-I). While the complete mechanism of the NS1:RIG-I interaction remains unclear, we were the first to demonstrate a direct interaction between the NS1 RNA-binding domain (NS1RBD) from the 1918H1N1 influenza virus and the second caspase activa-tion and recruitment domain (CARD2) of RIG-I using NMR. In addition, we also identi-fied that mutation of Arg 21 in the 1918H1N1 NS1RBD to Gln (R21Q) completely abrogated the NS1:CARD2 interaction. Given that CARD2 plays a …