Open Access. Powered by Scholars. Published by Universities.®
- Keyword
-
- Acute kidney injury (3)
- Chronic kidney disease (3)
- Glioblastoma (3)
- Glycosylation (3)
- CFTR (2)
-
- Epigenetics (2)
- Ferroptosis (2)
- Heavy chain ferritin (2)
- Influenza (2)
- Interferon (2)
- Iron (2)
- Myeloid cells (2)
- N-glycosylation (2)
- ST6Gal-I (2)
- 3D printing (1)
- 5hmC (1)
- ATM (1)
- Acetylcholine (1)
- Acinar to ductal metaplasia (1)
- Aging (1)
- Alpha-7 acetylcholine receptor (1)
- Alzheimer's (1)
- Amyloid-beta (1)
- Antioxidant (1)
- Antiviral (1)
- Apoptosis (1)
- Arrhythmia (1)
- Aryl hydrocarbon receptor (1)
- Autism (1)
Articles 31 - 52 of 52
Full-Text Articles in Medicine and Health Sciences
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 …
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 …
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) …
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 …
Using Peptide Mimetics To Probe Protein-Protein Interactions Significant In Cancers, Robert H. Whitaker
Using Peptide Mimetics To Probe Protein-Protein Interactions Significant In Cancers, Robert H. Whitaker
All ETDs from UAB
Protein-protein interactions are critical for cell life. One aspect of cellular regulation where such protein-protein interactions occur is in the highly regulated process of programmed cell death (or apoptosis). Apoptosis is critical for normal tissue homeostasis, differentiation, and if dysregulated is a driver of disease including cancers. At the center of apoptotic regulation is the BCL2 protein family whose intra-familial protein-protein interactions balance cell stress signaling either allowing the cell to survive or inducing mitochondrial cell death. These BCL2 protein interactions are accomplished through the BH3 motif. While unique to the BCL2 family, a similar motif, the reverse BH3, has …
The Role Of Protein O-Glcnacylation In Regulating Mitochondrial Function, Jalessa Nicole Wright
The Role Of Protein O-Glcnacylation In Regulating Mitochondrial Function, Jalessa Nicole Wright
All ETDs from UAB
The attachment of O-linked-N-acetylglucosamine (O-GlcNAc) to the serine/threonine residues of proteins has emerged as an important regulatory mechanism in transcriptional regulation, protein activation as well as cell survival. Several studies have reported that elevated O-GlcNAc levels have adverse effects on mitochondrial function. These negative effects have been linked to O-GlcNAc modification of mitochondrial proteins that are integral across multiple metabolic cell processes i.e. VDAC, NDUFA9 and DRP-1. Mitochondrial complexes I, III and IV all contain subunit proteins that are O-GlcNAc modified and increased O-GlcNAcylation of these proteins is associated with deficits in oxidative phosphorylation in these models. Conversely, it has …
The Role Of Suppressor Of Cytokine Signaling 3 In Neuroinflammatory Disease, Zhaoqi Yan
The Role Of Suppressor Of Cytokine Signaling 3 In Neuroinflammatory Disease, Zhaoqi Yan
All ETDs from UAB
The Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) pathway plays a critical role in cytokine-mediated responses in both innate and adaptive immunity, and dysregulation of the JAK/STAT pathway is linked to many inflammatory disorders. Multiple Sclerosis (MS) is an inflammatory demyelinating disease that affects the central nervous system, and both innate and adaptive immunity are involved in disease progression. STAT3 signaling is critically involved in MS pathology and is negatively regulated by Suppressor Of Cytokine Signaling 3 (SOCS3). Both increased STAT3 activation and reduced SOCS3 expression are observed in immune cells from patients with MS. Although the role of …
Novel Biomarkers For Parkinson Disease, Shijie Wang
Novel Biomarkers For Parkinson Disease, Shijie Wang
All ETDs from UAB
Parkinson disease (PD) is the second most common neurodegenerative disorder with no reliable biochemical biomarkers for disease prediction or progression, nor disease-modifying treatments to slow the relentless progression. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are known to increase LRRK2 kinase activity and increase the risk for late-onset PD. In this thesis, I discovered that LRRK2 is secreted into exosomes in urine and CSF, where LRRK2 kinase activity, reflected by autophosphorylation at pS1292 site, is preserved and reflective of cytosolic LRRK2 levels. In a cohort of biosamples from LRRK2 mutation carriers and matched controls, with and without PD, …
Context Fear Memory Formation Is Regulated By Hippocampal Lncrna-Mediated Histone Methylation Changes, Anderson Alan Butler
Context Fear Memory Formation Is Regulated By Hippocampal Lncrna-Mediated Histone Methylation Changes, Anderson Alan Butler
All ETDs from UAB
The post-translational modification of histones regulates gene expression and is critical for the formation and maintenance of hippocampus-dependent long-term memories. Changes in gene-specific expression of various epigenetic marks during the aging pro-cess are sufficiently consistent as to be used as an aging landmark or epigenetic clock in both humans and other species; however, the molecular mechanisms which govern the application of these marks aging are poorly explored. Recently, long noncoding RNAs (lncRNAs) have been implicated as regulators of histone methyltransferases and other chromatin-modifying enzymes (CMEs). Despite the relevance of such mechanisms to both aging and memory formation, the behavioral relevance …
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 …
Genome Sequencing To Identify Novel Developmental Disorder Variation, Matthew Neu
Genome Sequencing To Identify Novel Developmental Disorder Variation, Matthew Neu
All ETDs from UAB
The ability to quickly and accurately catalog an individual's genetic variation through genome sequencing has ignited a new era of diagnostic and therapeutic development for heritable disease. Although genome sequencing can provide a molecular diagnosis in a significant number of patients with suspected genetic disease, there remain a number of unsolved cases for which no pathogenic cause can be determined. This uncertainty can create a "diagnostic odyssey" in which sequential tests fail to provide a diagnostic resolution and can often delay beneficial treatment, impact family planning, and be emotionally challenging for patients and their families. Clearly, there is an unmet …
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 …
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, …
O-Glcnac Regulation Of Inhibitory Circuits, Kavitha Abiraman
O-Glcnac Regulation Of Inhibitory Circuits, Kavitha Abiraman
All ETDs from UAB
Post translational modification of proteins plays a crucial role in regulating their function, and the role of one such modification, termed O-GlcNAcylation, is understudied. O-GlcNAcylation involves the dynamic cycle of adding and removing an O-linked N-acetylglucosamine (O-GlcNAc) by the enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which are highly expressed in the hippocampus. Enzymes that catalyze O-GlcNAcylation are found at both presynaptic and postsynaptic sites, and O-GlcNAcylated proteins localize to synaptosomes. We have shown that acute and selective increase in O-GlcNAcylation of AMPAR GluA2 subunits underlies expression of a novel form of LTD at CA3-CA1 synapses (O-GlcNAc LTD), as well …