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Full-Text Articles in Medical Sciences
Investigating Hiv-1 Transmission To Human Cervix Using Reporter Virus Technologies, Dana Frances Indihar
Investigating Hiv-1 Transmission To Human Cervix Using Reporter Virus Technologies, Dana Frances Indihar
All ETDs from UAB
Around 39 million people globally are currently infected with Human immunodeficiency virus 1 (HIV-1), more than half of whom are women. HIV-1 is a retrovirus that infects and depletes an individual’s immune cells, culminating in the development of acquired immunodeficiency syndrome (AIDS) if not managed with anti-retroviral therapies (ART). Most women acquire HIV-1 through heterosexual intercourse. However, the early mechanisms and virologic determinants of HIV-1 transmission to women remain unclear. Herein, we demonstrate transmitted/founder (TF) HIV-1 representing two genetically and pathogenically distinct subtypes (A and D) in vivo have distinct replication phenotypes in an ex vivo cervical explant tissue (CET) …
Non-Catalytic Regulators Of The Secretory Pathway, Peyton Vanwinkle
Non-Catalytic Regulators Of The Secretory Pathway, Peyton Vanwinkle
All ETDs from UAB
This thesis focuses on two key questions: 1) how are bone development and regeneration regulated by the CREB3L1 transcription factor; and 2) what is the mechanism of action of the endoplasmic reticulum resident protein JAGN1, which when dysregulated, causes severe congenital neutropenia (SCN)? CREB3L1 regulates bone development and regeneration in mammalian models by facilitating the expression of COL1A1 and components of the secretory pathway required for collagen secretion. We generated two zebrafish models of Creb3l1 dysfunction (creb3l1ΔbZIP/ΔbZIP and creb3l1TA+/TA+). Both models showed that Creb3l1 functions in regulating col1a1a transcription and overall regenerate size are conserved in zebrafish. However, we also …
The Multifaceted Role Of Neutrophil Heterogeneity In Covid-19 Pathogenesis, Marcus Darrell Davis
The Multifaceted Role Of Neutrophil Heterogeneity In Covid-19 Pathogenesis, Marcus Darrell Davis
All ETDs from UAB
COVID-19 is a respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The disease is characterized by an excessive inflammatory response and dysfunction of the immune system triggered by immunopathological mechanisms. Neutrophils are the most abundant circulating leukocytes, playing a critical role in the pathogenesis of multiple inflammatory conditions. Several studies have demonstrated that neutrophils are key contributors to COVID-19 disease pathogenesis; however, their role in disease progression remains unclear. Here, we demonstrate immune dysregulation in COVID-19 patients characterized by a significant expansion of neutrophil numbers and reduced frequency of T-cell populations. We identify an immature …
Unmasking Molecular Mechanisms Of Multiple Maladies Through Multiomic Methodologies, Luke Potter
Unmasking Molecular Mechanisms Of Multiple Maladies Through Multiomic Methodologies, Luke Potter
All ETDs from UAB
Much modern biomedical research is invested in determining causative molecular mechanisms and identifying potential therapeutics within human disease or injury. Traditional experiments such as over-expressing or “knocking out” the level of a gene’s abundance can determine the specific contribution of a single gene to a pathology and are a vital component of scientific research. However, taking a big picture approach through the application of ‘omics technologies can lead to a broader overall understanding of a pathology and can potentially generate numerous specific hypotheses to be tested using the more traditional molecular approaches. In this dissertation, transcriptomic and epigenomic technologies, measuring …
The Role Of Fibroblast Growth Factor Receptors In Inflammatory Airway Diseases, Molly Easter
The Role Of Fibroblast Growth Factor Receptors In Inflammatory Airway Diseases, Molly Easter
All ETDs from UAB
Chronic inflammation plays a role in the development and progression of airway diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). COPD is caused primarily by chronic cigarette smoke exposure. Conversely, CF is a single gene disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Although the causes of COPD and CF are different, there are common pathological features. Studies show that chronic inflammation plays a significant role in the pathogenesis of both COPD and CF. Moreover, chronic inflammation induces ageing-associated pathomechanisms like cellular senescence, which exacerbates chronic inflammation. Previous work demonstrates that …
Diagnostic Imaging Approaches: Pet Imaging In Monitoring Immune Responses In Oncology And Tuberculosis, Chanelle Hunter
Diagnostic Imaging Approaches: Pet Imaging In Monitoring Immune Responses In Oncology And Tuberculosis, Chanelle Hunter
All ETDs from UAB
Positron emission tomography (PET) imaging agents play a transformative role in personalized medicine through their application in disease diagnosis and immunotherapy monitoring, focusing on chemokine receptors, TH1-activated immune cells, and tuberculosis (TB) diagnostics. In immuno-oncology, accurately assessing TH1-activated immune cells in the tumor microenvironment (TME) is vital for evaluating cancer immunotherapy efficacy. Chemokine receptors, crucial in cellular signaling and inflammatory reactions, play a significant role in TH1 responses, thus serving as a potential area of interest in elucidating these anti-tumor responses. Through our work a novel CXCR3-targeting immunoPET probe, [89Zr]DFO-αCXCR3, was developed to detect and quantify these cells. This probe …
Phosphate Drives Pulmonary Inflammation Through Fgfr1, Erk, And Akt Signaling, Seth Bollenbecker
Phosphate Drives Pulmonary Inflammation Through Fgfr1, Erk, And Akt Signaling, Seth Bollenbecker
All ETDs from UAB
Chronic kidney disease (CKD) is characterized as irreversible progressive loss of renal function and affects over one tenth of the global population. Although CKD-associated comorbidities contribute significantly to its mortality, the lungs are often not considered. Lung diseases make up three of the top six leading causes of death worldwide and share many comorbidities with CKD. Clinical reports show that CKD patients are more likely to develop obstructive and restrictive lung diseases, but the mechanisms underlying this propensity for CKD-associated pulmonary complications are unknown. Hyperphosphatemia and associated elevations of fibroblast growth factor (FGF) 23, two of many consequences of reduced …
The Impact Of O-Glcnac Signaling On Dna Hydroxymethylation In Temporal Lobe Epilepsy, Rudhab Bahabry
The Impact Of O-Glcnac Signaling On Dna Hydroxymethylation In Temporal Lobe Epilepsy, Rudhab Bahabry
All ETDs from UAB
Temporal Lobe Epilepsy (TLE) is the most prevalent form of focal epilepsy and the most treatment-resistant type. This condition is characterized by recurrent, unprovoked seizures typically originating in the hippocampus. Epigenetic modifications such as DNAme changes have been implicated in brain functions such as synaptic plasticity, learning and, memory, and cognition. The oxidation of DNA 5-methylcytosine (5-mC) and its oxidized form, 5-hydroxymethylcytosine (5-hmC) catalyzed by Ten-Eleven Translocation (TET) family of dioxygenases and linked to epilepsy's hyperexcitable state. Post‐translational modifications (PTMs) of proteins, such as O-GlcNAcylation, facilitate cells' immediate responses to intracellular or extracellular environmental stimuli by modifying the functions of …
Novel Roles Of Rab35 In Development And Disease, Kelsey Ruth Clearman
Novel Roles Of Rab35 In Development And Disease, Kelsey Ruth Clearman
All ETDs from UAB
As the largest and most dynamic family of GTPases within the mammalian cell, Rabs play an essential role as molecular switches in regulating intracellular vesicular trafficking and serve as significant signaling transducers. Over the last few decades, Rabs have been identified to regulate endocytic, transcytosis, and exocytotic pathways, and mutations in Rabs, or alterations in downstream effectors lead to embryonic lethality and diseases such as cancer and ciliopathies. Ciliopathies are a class of pathologies that result from defects in structure or function of the primary cilia. Primary cilia, found on virtually all mammalian cells, is a microtubule-derived appendage that relies …
The Modification Of Single Domain Antibody Framework And Variable Regions To Impart Novel Pharmacodynamic And Pharmacokinetic Properties, Lucinda Ann Hall
The Modification Of Single Domain Antibody Framework And Variable Regions To Impart Novel Pharmacodynamic And Pharmacokinetic Properties, Lucinda Ann Hall
All ETDs from UAB
In recent years, nanobodies have become important theranostic molecules, and research has focused on improving their pharmacokinetics and binding for novel targets. Nanobodies are characterized by their high kidney uptake, leading to potentially unsafe exposure of the kidneys when delivering cytotoxic payloads. Researchers hypothesize that positively charged amino acids contribute to this kidney uptake. To address this, we assessed the impact of substituting lysine residues within the 2Rs15d HER2 nanobody scaffold to alanine on its in vivo pharmacokinetics using positron emission tomography (PET) imaging. We found that nanobodies bearing lysine-to-alanine substitutions maintained their affinity for HER2. Characterization of the K88A …
Catecholamines And Catecholamine Resistance In Animal Models Of Metabolic Syndrome, Robert Follett Rosencrans
Catecholamines And Catecholamine Resistance In Animal Models Of Metabolic Syndrome, Robert Follett Rosencrans
All ETDs from UAB
The sympathetic nervous system is a key regulator of energy homeostasis, in part, through the control of white adipose tissue lipolysis. Sympathetic nerves modulate adipose tissue physiology through the release of catecholamines, particularly norepinephrine, onto alpha- and beta-adrenergic receptors (a-AR; B-AR). Lipolysis refers to the breakdown of triglycerides into glycerol and free fatty acids, often in response to activation of B2/3-AR. Beta adrenergic activation of lipolysis is widely known to be impaired in patients with metabolic syndrome and animal models thereof (catecholamine resistance). Recent studies have demonstrated that catecholamine regulation of adipokine release is also disrupted, suggesting that catecholamine resistance …
The Role Of Altered Cell-Cell Communication Between Glia And Neurons In Alzheimer’S Disease, Tabea Marga Soelter
The Role Of Altered Cell-Cell Communication Between Glia And Neurons In Alzheimer’S Disease, Tabea Marga Soelter
All ETDs from UAB
Alzheimer’s disease is the most prevalent neurodegenerative disease and is characterized by progressive memory loss and cognitive decline, affecting behavior, speech, and motor abilities. The neuropathology includes the formation of extracellular amyloid-β plaques and intracellular neurofibrillary tangles of phosphorylated tau. Additionally, neurons become functionally impaired before degenerating and dying. While neuronal loss is a disease hallmark, glia maintain neuronal health and homeostasis through cell-cell communication with neurons. Cellular crosstalk is mediated through the release of chemical intermediates (i.e., ligands), which are taken up by cell surface membrane receptors. Previous studies have shown dysregulation of global cell-cell communication patterns and communication …
Investigating The Electrostatics Of Mucins As Key Contributors To Mucus Stasis In Cystic Fibrosis, Elex Skylar Rose
Investigating The Electrostatics Of Mucins As Key Contributors To Mucus Stasis In Cystic Fibrosis, Elex Skylar Rose
All ETDs from UAB
Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a channel responsible for the transport of chloride and bicarbonate ions across the apical cell surface. In the respiratory tract, defective CFTR results in viscous and adherent mucus that becomes static within the airway, which leads to chronic infections, progressive lung damage, and early mortality. Historically, CF mucus stasis has been attributed to significant airway dehydration; however, growing evidence has demonstrated that aberrant electrostatic properties of mucins also contribute to mucus stasis in CF. Mucins are large, polymeric glycoproteins …
Regulating Cancer Cell Metabolism During Hypoxia-Reoxygenation: Examing The Interplay Of Gasotransmitters And Glutaminolysis, Dianna L. Xing
Regulating Cancer Cell Metabolism During Hypoxia-Reoxygenation: Examing The Interplay Of Gasotransmitters And Glutaminolysis, Dianna L. Xing
All ETDs from UAB
Oxidative phosphorylation is an oxygen-dependent metabolic process that provides the majority of ATP used to support essential cellular functions. However, in cancer, limitations in oxygen availability occur during the development and metastasis of tumors. To compensate for the demands of rapidly proliferating cells, many cancers exhibit an increased demand for glycolysis, the TCA cycle, and glutaminolysis. In this thesis, extracellular flux technology and metabolomics were applied in a hypoxia-reoxygenation model to investigate the metabolic adaptations that occur in dynamic changes in oxygen and nutrient availability in cancer cells. We show the significance of glutaminolysis and its substrates in regulating cancer …
Transcriptional Regulation In Early Stage Cd4+ T Cell Activation And Differentiation, Andrew Ray Schroeder
Transcriptional Regulation In Early Stage Cd4+ T Cell Activation And Differentiation, Andrew Ray Schroeder
All ETDs from UAB
CD4+ T cells regulate the humoral and cellular immune responses by differentiating into T follicular helper (Tfh) cells or into non-Tfh effector cells. Non-Tfh effector cells leave the lymph node and migrate to the effector site whereas Tfh cells upregulate CXCR5 and migrate towards the B cell follicle. The mechanism of CXCR5 induction, however, is still incompletely understood. The transcription factor Bach2 was shown to inhibit the in vitro differentiation of Th1, Th2, and Th17 cells as well as the in vivo Tfh responses. Though, it is unknown how Bach2 arbitrates Tfh and non-Tfh differentiation in vivo. Here, we report …
The Effects Of Cannabidiol On Brain Temperature In Treatment-Resistant Epilepsy, Ayushe A. Sharma
The Effects Of Cannabidiol On Brain Temperature In Treatment-Resistant Epilepsy, Ayushe A. Sharma
All ETDs from UAB
Epilepsy affects over 70 million people worldwide with a global incidence of 2.4 million new cases per year. In many of these patients, neuroinflammation (NI) is a key pathological contributor to focal seizure generation and maintenance. Sustained NI degrades the blood–brain barrier, leads to neuronal death, and ultimately decreases seizure threshold. Finding ways to image and treat NI is especially important for the >30% of patients with treatment-resistant epilepsy (TRE) who cannot achieve seizure freedom with standard antiseizure medications. Cannabidiol (CBD) effectively reduces seizure frequency and severity in many TRE patients, although its antiepileptic effects remain poorly understood. Atypically high …
Interactions Between Pseudomonas Aeruginosa And The Oral Commensal Streptococcus Salivarius, Sara Noelle Stoner
Interactions Between Pseudomonas Aeruginosa And The Oral Commensal Streptococcus Salivarius, Sara Noelle Stoner
All ETDs from UAB
The cystic fibrosis airway is a polymicrobial environment often dominated by opportunistic pathogens such as Pseudomonas aeruginosa, a leading cause of lung function decline and mortality in persons with CF. Commensal streptococcal colonization has been associated with stable CF lung function in multiple studies. However, few studies have examined interactions between P. aeruginosa and commensals as well as their impact on P. aeruginosa airway infections. In the first half of this work, we studied interactions between P. aeruginosa and the oral commensal Streptococcus salivarius within a biofilm setting. We found that S. salivarius biofilm formation is promoted by the non-mucoid …
Investigating The P53 Tumor-Suppressive Network And The Dynamics/Mechanism Of P53 Loss Of Heterozygosity, Jun Wang
All ETDs from UAB
Tumor suppressor gene TP53 is the most frequently mutated gene across human cancers (~50%). Patients with Li-Fraumeni syndrome (LFS) who carry germline p53 mutations exhibit a diverse spectrum of childhood- and adult-onset malignancies. Despite over 40 years of dedicated studies to understand the role of p53 in tumor prevention, there are still many unanswered questions regarding the underlying mechanisms of p53. Previous studies have supported the notion that p53 exerts its tumor-suppressive function through its transcriptional activities. Therefore, strategies to enhance p53’s functions in tumor suppression via manipulating of downstream target gene activities in cancers show promising. To better investigate …
Cis-Regulatory Elements: Relevance For Alzheimer's Disease, Brianne Brazell Rogers
Cis-Regulatory Elements: Relevance For Alzheimer's Disease, Brianne Brazell Rogers
All ETDs from UAB
Alzheimer’s disease (AD) is the most common neurodegenerative disease, currently affecting more than six million Americans with limited treatment options. Identifying genetics contributors to neurodegenerative diseases has contributed critical insights into potential disease mechanisms. The majority of disease-associated genetic variants are located in non-coding regions, likely in regulatory elements, and affect the expression of target genes whose function contributes to neurodegeneration. Here, I performed a case-control study utilizing nuclei from dorsolateral prefrontal cortex postmortem tissue to correlate chromatin accessibility with gene expression and nominate 40,831 AD-specific candidate cis-regulatory elements. Additionally, work in this dissertation nominates ZEB1 and MAFB as candidate …
Understanding The Dual Role Of The Oncolytic Viruses And Natural Killer Cells In Targeting Neuroblastoma, Colin Harrington Quinn
Understanding The Dual Role Of The Oncolytic Viruses And Natural Killer Cells In Targeting Neuroblastoma, Colin Harrington Quinn
All ETDs from UAB
Pediatric cancer is the leading cause of death by disease in children, and neuroblastoma accounts for roughly 15% of pediatric cancer related deaths. Neuroblastoma is a malignancy of neural crest origin and develops in the ganglia of the peripheral nervous system, most commonly arising in the adrenal glands. Advancements in therapy have significantly improved outcomes for children with low-risk neuroblastoma but for those with high-risk refractory, or relapsed disease, survival outcomes remain dismal and intervention with toxic chemotherapeutics often result in long term morbidities. The need for improved therapies for this patient population is dire. Immunotherapies offer a novel approach …
Imaging Nanoscale Plasma Membrane Dynamics Reveals Diversity In Clathrin-Coated Vesicle Formation, Tomasz Jacek Nawara
Imaging Nanoscale Plasma Membrane Dynamics Reveals Diversity In Clathrin-Coated Vesicle Formation, Tomasz Jacek Nawara
All ETDs from UAB
Clathrin-mediated endocytosis (CME) is an essential cellular process facilitating the internalization of a variety of cargo. Clathrin polymerization and changes in plasma membrane architecture and composition are necessary steps to mediate the formation of clathrin-coated vesicles (CCVs). However, simultaneous analysis of clathrin dynamics and membrane structure in living cells is challenging due to the limited axial resolution of fluorescence microscopes and the heterogeneity of CME. This has fueled conflicting models of vesicle assembly and obscured the roles of flat clathrin assemblies. Here we use Simultaneous Two-wavelength Axial Ratiometry (STAR) microscopy to bridge this critical knowledge gap by quantifying the nanoscale …
Manipulation And Dependence On Host Cell Cycle By Human Rna And Dna Viruses: Human Coronavirus Oc43 And Bk Polyomavirus, Jason M. Needham
Manipulation And Dependence On Host Cell Cycle By Human Rna And Dna Viruses: Human Coronavirus Oc43 And Bk Polyomavirus, Jason M. Needham
All ETDs from UAB
Cell cycle is a universal necessity of cellular life and impacts nearly every process within the cell. However, despite over one hundred years of research, there still remain questions concerning the mechanisms and regulation of eukaryotic cell cycle. From the beginning, viruses have informed our knowledge of cell cycle. Many key regulators such as the E2F transcription factors, Src kinase, and p53 were originally discovered while studying the interactions between viruses and the cell. Herein, we continue the investigation of viral interactions with cell cycle machinery by researching an RNA virus and a DNA virus. These viruses, human coronavirus OC43 …
Structural Characterization Of Autoreactive Igg Fabs In The Context Of Iga Nephropathy, Jordan Lingo
Structural Characterization Of Autoreactive Igg Fabs In The Context Of Iga Nephropathy, Jordan Lingo
All ETDs from UAB
IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world, yet there is no cure and treatment options are limited. Advances in understanding of the molecular basis of this pathology may lead to potential novel therapeutics, but there is still much we don’t know about the disease and the underlying biology. The current paradigm explaining the molecular stages leading to IgAN is called the “multi-hit hypothesis,” which involves the following four hits: (1) Elevated levels of circulating IgA1 with some O-linked glycans deficient in galactose moieties (galactose-deficient IgA1, Gd-IgA1). (2) Circulating IgG autoantibodies (autoAbs) specific to the Gd-IgA1 …
A Tale Of Two Waves: The Role Of Genomic Enhancers In Regulating Transcriptional And Epigenetic Responses To Neuronal Activitiy, Robert A. Phillips
A Tale Of Two Waves: The Role Of Genomic Enhancers In Regulating Transcriptional And Epigenetic Responses To Neuronal Activitiy, Robert A. Phillips
All ETDs from UAB
The mesolimbic dopamine (DA) pathway, which consists of dopaminergic neurons that project from the ventral tegmental area (VTA) to the nucleus accumbens (NAc), is heavily implicated in drug addiction. Exposure to drugs of abuse results in increases in extracellular concentrations of DA in the NAc, which in turn activates an immediate early gene (IEG) expression program that primarily consists of activity-dependent transcription factors, such as the AP1 subunits Fos and JunB. IEGs engage a set of temporally and functionally distinct genes, termed the late response gene (LRG) expression program. While gene expression changes are critical for drug-dependent adaptations, two major …
T-Bet Regulates The Maintenance And Asc Differentiation Potential Of The Lymph Node And Lung Memory B Cell Compartments, Christopher A. Risley
T-Bet Regulates The Maintenance And Asc Differentiation Potential Of The Lymph Node And Lung Memory B Cell Compartments, Christopher A. Risley
All ETDs from UAB
Although human memory B cells (Bmem), including extrafollicular DN2 cells and CD27+ effector Bmem (eBmem), express T-bet, its role in Bmem biology is not understood. We characterized transcriptionally distinct clusters of mature, somatically mutated nucleoprotein (NP)-specific Bmem in LNs of influenza-infected mice. None of the Bmem expressed plasma cell (PC) lineage commitment factors, but one cluster was significantly enriched for Tbx21+ cells that exhibited a molecular signature similar to the previously described human T-bet+ eBmem. Metabolic reprogramming, protein synthesis and the mTOR-dependent unfolded protein response gene networks were all upregulated in Tbx21+ NP+ mouse Bmem. Using constitutive and inducible models …
The Molecular And Structural Basis Of B Cell Epitope Targeting In Transplant Rejection, John T. Killian
The Molecular And Structural Basis Of B Cell Epitope Targeting In Transplant Rejection, John T. Killian
All ETDs from UAB
HLA-reactive antibodies (HLA-Abs) to mismatched polymorphic HLA molecules are one of the major barriers to successful organ transplantation. However, key knowledge gaps remain surrounding the immunology of the anti-HLA B cell response in transplant rejection. This lack of understanding regarding the phenotype and specificity of the anti- HLA B cell response means that the field cannot develop optimal therapies to treat B-cell mediated donor-specific responses and that it lacks the tools to optimally match donors and recipients to prevent rejection events. Therefore, this dissertation aimed to explore the clinical factors associated with the formation of donor-specific antibodies and the molecular …
Understanding Molecular Mechanisms Of Glioblastoama Resistance To Design Novel Combinatorial Therapies, Amber B. Jones
Understanding Molecular Mechanisms Of Glioblastoama Resistance To Design Novel Combinatorial Therapies, Amber B. Jones
All ETDs from UAB
Treatment options for the universally lethal brain tumor, glioblastoma (GBM), are severely limited and often unsuccessful in fully eradicating the disease. Extremely aggressive in nature, GBM cells often implore suppressive mechanisms to evade therapeutic detection which aids in the dismal 15-month median survival rate. Facilitating disease severity and more importantly, disease recurrence, are the immunosuppressive and chemoresistant phenotypes of GBM cells. Specifically, the DNA alkylating agent, temozolomide (TMZ) possesses lymphodepleting properties shunting robust immune cell infiltration into an immunologically cold tumor microenvironment. Additionally, through inherent or acquired mechanisms, GBM tumors commonly become resistant to the DNA damaging effects of TMZ …
The Long Non-Coding Rna Neat1 Mediates Astrocyte Gene Expression And Hippocampus-Dependent Memory In Aging And Alzheimer's Disease, Ashleigh Burns Irwin
The Long Non-Coding Rna Neat1 Mediates Astrocyte Gene Expression And Hippocampus-Dependent Memory In Aging And Alzheimer's Disease, Ashleigh Burns Irwin
All ETDs from UAB
Dysregulation of long non-coding RNAs (lncRNAs) is increasingly associated with cognitive dysfunction and neurodegenerative disorders such as Alzheimer’s disease (AD). The highly evolutionarily conserved lncRNA Nuclear-Enriched Abundant Transcript 1 (NEAT1) is expressed not only in a tissue- and temporally-specific manner, but also celltype specific manner. Despite the predominance of NEAT1 in glial populations, and the significant role astrocytes play in memory, relatively little is known about Neat1 regulation of astrocyte transcriptomics during age-related memory. Here, we report a crucial role of the lncRNA Neat1 in astrocyte dysfunction and memory deficits associated with both normal aging and AD. Expression of Neat1 …
Optimization Of Progranulin Gene Therapy, A Potential Treatment For Frontotemporal Dementia, Shreya Natesh Kashyap
Optimization Of Progranulin Gene Therapy, A Potential Treatment For Frontotemporal Dementia, Shreya Natesh Kashyap
All ETDs from UAB
Heterozygous loss of function mutations in the progranulin gene cause frontotemporal dementia, characterized by deficits in social behavior, language comprehension and motor function. Almost every frontotemporal dementia-related progranulin mutation is loss of function and results in progranulin haploinsufficiency. For this reason, progranulin replacement is a conceptually straightforward therapeutic strategy for patients with frontotemporal dementia caused by progranulin mutations. Here, we outline progranulin biology, progranulin deficient mouse models of frontotemporal dementia and preclinical interventions centered around increasing brain progranulin levels. We have demonstrated that blocking the progranulin C-terminus, which harbors the sortilin binding site, improves the cross-correctional capacity of neurotropic progranulin …
Molecular Influences Of Racial Disparities In Pancreatic Neuroendocrine Tumors, Brendon Herring
Molecular Influences Of Racial Disparities In Pancreatic Neuroendocrine Tumors, Brendon Herring
All ETDs from UAB
Pancreatic Neuroendocrine Tumors (PNETs) are highly heterogeneous neoplasms arising from the hormone-secreting cells of the endocrine pancreas. PNETs are broadly categorized as functional and non-functional based on the presence of symptoms associated with hormone secretion, which occurs in approximately 30% of cases. While functional tumors are all considered for resection because of these symptoms and their associated sequelae, non-functional tumors > 2cm are currently resected based on increased risk of developing metastatic disease. However, this criterion is based on data from predominantly White patients. Recent studies have shown that Black patients have much higher rates of lymph node metastatic disease at …