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Full-Text Articles in Medicine and Health Sciences
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 …
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 …
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 …
Acetylcholine Signaling In Glioblastoma Invasion And Peritumoral Hyperexcitability, Emily Grace Thompson
Acetylcholine Signaling In Glioblastoma Invasion And Peritumoral Hyperexcitability, Emily Grace Thompson
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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. …
Modulation Of Klotho Affects Dendritic Spine Remodeling And Neuronal Network Activity, Hai T. Vo
Modulation Of Klotho Affects Dendritic Spine Remodeling And Neuronal Network Activity, Hai T. Vo
All ETDs from UAB
Klotho protein expression has profound effects on lifespan where klotho-deficient mice exhibit premature aging phenotypes and live only to ~8 weeks of age while klotho-overexpressing mice have lifespans that are at least 20% longer than wild-type mice. Klotho expression also has similar effects on cognitive function as klotho-deficient mice develop cognitive impairment by 7 weeks of age and klotho-overexpressing mice show enhanced cognitive function. These effects also extend to humans as polymorphisms that alter circulating levels of klotho have likewise effects on lifespan and brain function. Despite the fact that modulation of klotho expression has reciprocal effects on cognitive function, …
Pannexin 1 Channel Inhibition To Prevent Triggered Arrhythmia, Grace Elizabeth Salzer
Pannexin 1 Channel Inhibition To Prevent Triggered Arrhythmia, Grace Elizabeth Salzer
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The mechanism of triggered arrhythmia generation involves inappropriate diastolic calcium (Ca2+) releases from the sarcoplasmic reticulum that promote membrane depolarization when the released Ca2+ is transported out of the cardiomyocyte via the sodium Ca2+ exchanger (NCX). If membrane depolarization is large enough, these events can trigger an ectopic action potential. However, it is not fully understood what physiological factors facilitate triggered events at the tissue level. Pannexin 1 (Px1), a large transmembrane conductance channel, can be activated by various stimuli including increases in intracellular Ca2+. We predict that during diastolic Ca2+ releases, Px1 becomes activated and together with the NCX, …
The Influence Of O-Glcnacylation On Dna 5-Hydroxymethylation In The Epileptic Hippocampus, Richard Gilbert Sanchez
The Influence Of O-Glcnacylation On Dna 5-Hydroxymethylation In The Epileptic Hippocampus, Richard Gilbert Sanchez
All ETDs from UAB
Epilepsy is a neurological disorder that affects roughly 3 million Americans and 65 million individuals worldwide. Although there are several known causes of epilepsy, little is understood about the development of epilepsy or epileptogenesis. What has been observed through multiple studies of epilepsy is an alteration of the proteomic profile, along with a distinct change in post-translational modifications (PTM). Studies have focused on phosphorylation and a variety of kinases that are upregulated during epilepsy with little clinical translation. This dissertation investigates O-GlcNAcylation, a PTM that is highly intertwined with the cellular metabolism, and its epigenetic effects on gene expression via …
Integration Of Yeast Phenomics And Cancer Pharmacogenomics To Model Precision Medicine, Sean Santos
Integration Of Yeast Phenomics And Cancer Pharmacogenomics To Model Precision Medicine, Sean Santos
All ETDs from UAB
Precision medicine aims to optimize disease treatment by considering the differential influence of functional genetic variation on phenotypic outcomes and therapeutic efficacy. However, current precision medicine paradigms lack consideration of the abundance of genetic interaction and ensuing complexity of phenotypes, thus thwarting resolution of gene-drug interaction at a systems level and ‘precise’ predictions for most patients. Yeast phenomics enables quantitative, high-resolution experimental modeling of gene-drug interaction phenotypes at a systems level by measuring growth curves for the ~6000 yeast knockout/knockdown library strains, which can guide a more global resolution of disease and treatment complexity at the organism level. We postulate …
Dysregulation In The Central Nervous System Upon Mcmv Infection In Newborn Mice, Cathy Yea Won Sung
Dysregulation In The Central Nervous System Upon Mcmv Infection In Newborn Mice, Cathy Yea Won Sung
All ETDs from UAB
Human cytomegalovirus (HCMV) infection is a major cause of morbidity in infants and children throughout the world. Between 0.2-1.2% of all live births is infected with HCMV in the United States. Approximately 5-15% of these newborn babies will develop long-term neurological damage resulting in motor disorders, mental retardation, and sensorineural hearing loss. Although the neurological sequelae associated with congenital HCMV infections are well characterized, little is known about the pathogenesis of the damage to the central nervous system (CNS). To study the pathogenesis of congenital HCMV infection, we have developed a mouse model in which newborn mice are infected intraperitoneally …
The Anti-Tumor Effects Of Hur Inhibition In Glioblastoma, Jiping Wang
The Anti-Tumor Effects Of Hur Inhibition In Glioblastoma, Jiping Wang
All ETDs from UAB
Glioblastomas (GBMs) are the most malignant primary brain tumor. GBMs represent 14.7% of total primary CNS tumors and 47.7% of malignant CNS tumors. The median survival of GBM is 18-20 months, while five-year survival rate is only 5.6%. GBMs are maintained by glioma stem cells (GSCs), and poor treatment outcomes are linked to the high resistance of GSCs to radiation and chemotherapy, and the immunosuppressive tumor microenvironment. The mRNA binding protein HuR is a key regulator of tumor growth and development based upon the fact that HuR targets mRNAs that are broadly involved in tumorigenesis. We have previously shown that …
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 …
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 …
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 …
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 …
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. …
Dna Template Sequence Effects On Rna Polymerase I Transcription Elongation, Andrew Martin Clarke
Dna Template Sequence Effects On Rna Polymerase I Transcription Elongation, Andrew Martin Clarke
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The production of ribosomes represents the major synthetic effort of a rapidly dividing cell, and is intimately linked to the regulation of cell growth and proliferation. Developing a greater understanding of the mechanisms that regulate ribosome biogenesis is therefore crucial to understanding cellular control of the growth cycle. Ribosome biogenesis begins with the synthesis of the 35S ribosomal RNA (rRNA) by RNA polymerase I (Pol I). This RNA is co- and post-transcriptionally processed to produce the 18S, 5.8S, and 25S rRNAs. These RNAs are critical components of ribosomes, and Pol I has been demonstrated to be a key regulation target …
Regulation Of St6gal-I In Cancer: Sox2 Identified As Novel Driver Of St6gal-I Expression, Kaitlyn Alexandra Dorsett
Regulation Of St6gal-I In Cancer: Sox2 Identified As Novel Driver Of St6gal-I Expression, Kaitlyn Alexandra Dorsett
All ETDs from UAB
ST6Gal-I is a sialyltransferase that functions to add an 2-6 linked sialic acid to N-linked glycoproteins. The expression of ST6Gal-I is upregulated in many cancers at both the mRNA and protein levels. ST6Gal-I has also been shown to promote cancer stem cell (CSC) characteristics including chemoresistance, tumor-initiating potential, and spheroid growth. However, the transcriptional drivers of ST6Gal-I expression in stem-like cells remain largely unknown. Herein we highlight that SOX2 and ST6GAL1 are both located on one of the most commonly amplified chromosomal segments in cancer, amplicon 3q26. Copy number gains in both SOX2 and ST6GAL1 are observed in roughly 25% …
Regulation Of Intestinal Innate Lymphoid Cells In Acute And Chronic Inflammation, Sarah Dulson
Regulation Of Intestinal Innate Lymphoid Cells In Acute And Chronic Inflammation, Sarah Dulson
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The Innate Lymphoid Cell (ILC) population encompasses five subpopulations that are increasingly appreciated to participate in immune responses to inflammation and injury as well as directly influence homeostasis in tissues throughout the body. ILCs are enriched at mucosal surfaces, such as the gastrointestinal tract, where they are transcriptionally poised for rapid activation. Therefore, ILCs contribute significantly to protective responses to infection, and can exacerbate inflammation and disease when dysregulated. Herein, we demonstrate two pathways that regulate intestinal ILC phenotype and function and delineate the impact of these pathways on both protective and pathogenic roles of ILCs. Using a murine model …
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 …
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
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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
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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 …
Ventral Hippocampal Input To The Medial Prefrontal Cortex Regulates Social Memory, Mary Leann Phillips
Ventral Hippocampal Input To The Medial Prefrontal Cortex Regulates Social Memory, Mary Leann Phillips
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Both the ventral hippocampus (vHIP) and medial prefrontal cortex (mPFC) are active participants in the neural circuitry activated by social interaction, and are both necessary for certain aspects of social behavior. Additionally, synaptic projections from the ventral hippocampus (vHIP) to the medial prefrontal cortex (mPFC) are implicated in several neuropsychiatric disorders. Using the Mecp2 knockout (KO) mouse model of Rett syndrome, an autism-associated disorder with network level deficits in the vHIP and mPFC as well as aberrant social behavior, we strove to determine the role of vHIP-mPFC in social behavior. Here, we show that the vHIP-mPFC projection is hyperactive in …
The Reductive Stress Reducto-Mir: Emerging Insight Into Microrna-671, Justin Michael Quiles
The Reductive Stress Reducto-Mir: Emerging Insight Into Microrna-671, Justin Michael Quiles
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Excessive accumulation of reactive oxygen and nitrogen species (ROS/RNS) promotes cardiac pathophysiology. Although extreme oxidative burden is cytotoxic, ROS/RNS are continually generated within multiple domains of cardiac myocytes, and these species play fundamental roles in signal transduction through reversible thiol oxidation. Nuclear factor, erythroid 2 Like 2 (Nfe2l2/NRF2) is activated by ROS/RNS and binds cis regulatory antioxidant response elements (AREs) to induce the expression of a host of thiol oxidoreductases which regulate signaling events at the post-translational, transcriptional and epigenetic levels. Although oxidative stress has been linked to cardiac disease, adaptive processes in the heart require reduction-oxidation (redox) reactions as …
Transcriptional Dynamics Of Dopaminergic Signaling, Katherine Elizabeth Savell
Transcriptional Dynamics Of Dopaminergic Signaling, Katherine Elizabeth Savell
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Drugs of abuse increase dopamine concentrations in the nucleus accumbens, a key reward structure that integrates contextual and cue-related information and regulates motivated behavior. This surge of dopamine triggers cell signaling cascades that converge in the nucleus to cause changes in gene expression, which are thought to lead to the observed functional and structural alterations in the reward circuit after exposure to drugs of abuse. However, while various drugs of abuse cause transcriptional changes, previously available tools have not had the capacity to deeply characterize these gene programs. Therefore, we optimized a dual lentivirus CRISPR system for targeted gene modulation …
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
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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 …
Targeting The Nad Salvage Pathway For The Treatment Of The Parasitic Disease Schistosomiasis, Michael David Schultz
Targeting The Nad Salvage Pathway For The Treatment Of The Parasitic Disease Schistosomiasis, Michael David Schultz
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Schistosomiasis, also known as bilharzia, is the third most common parasitic infection worldwide and a major source of morbidity and mortality in developing countries. Caused by trematodes in the genus Schistosoma, this parasitic disease has no vaccine therapy and resources for drug development are scarce. Despite an unknown mechanism of action, praziquantal has become the primary source of treatment due to its efficacy against all species of Schistosoma. However, with increased drug resistance in endemic areas and low activity against immature parasites, relying on this single drug is unsustainable and risky. Hence, there is a growing need for new, safe …
Novel Approaches To Enhance Translational Readthrough Efficacy For Cystic Fibrosis Nonsense Mutations, Jyoti Sharma
Novel Approaches To Enhance Translational Readthrough Efficacy For Cystic Fibrosis Nonsense Mutations, Jyoti Sharma
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Cystic fibrosis (CF) is a monogenic autosomal recessive disease caused by over 1,900 naturally occurring variants in the CF transmembrane conductance regulator (CFTR). CFTR is an epithelial anion channel which regulates the movement of chloride and bicarbonate ions. Mutations in the CFTR causes diminished CFTR protein and/or reduced CFTR function that lead to clinical manifestations. These include severe epithelial dysfunction of multiple tissues, including the lungs, intestine, pancreas, and reproductive organs. Premature termination codons (PTC), or nonsense mutations, are among the most severe CFTR variants and occur in ~11% of the CF population. PTCs are caused by the presence of …
Therapeutic Mechanisms In Sickle Cell Nephropathy, Crystal Taylor
Therapeutic Mechanisms In Sickle Cell Nephropathy, Crystal Taylor
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Sickle cell disease (SCD) is a commonly inherited genetic blood disorder that causes hypoxia-induced polymerization of mutant hemoglobin resulting in erythrocyte sickling, transient microvascular occlusion, ischemic injury, and end-organ damage. Systemic endothelial dysfunction and vaso-occlusive episodes observed in SCD are particularly deleterious to the kidney, where the hypoxic, hyperosmotic environment of the medulla makes it particularly susceptible to ischemic injury. Over recent decades, chronic kidney disease has emerged as a significant contributor to mortality and morbidity in SCD patients. Despite a growing interest in the importance of sickle cell nephropathy (SCN), therapeutic options are limited and much remains undiscovered regarding …