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Articles 1 - 30 of 52
Full-Text Articles in Medicine and Health Sciences
Structural And Biochemical Charactereization Of Lrrk2, Zhiyong Liu
Structural And Biochemical Charactereization Of Lrrk2, Zhiyong Liu
All ETDs from UAB
Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are the most common known genetic cause of Parkinson disease (PD) , with pathogenic mutations located within each of the two catalytic cores of the protein, the GTPase and kinase domains. The most prevalent pathogenic mutation, G2019S increases kinase activity up to 5-fold, causing significant changes in the protein’s biochemical behavior. Other mutations such as R1441G and I2020T have also been demonstrated to increase LRRK2 kinase activity, however, the detailed mechanisms remains unclear. A major limitation in the field is the lack of structural information of LRRK2. This dissertation detailed …
Neurodevelopmental Alterations In A Rodent Model Of Temperamental Differences, Chelsea Mccoy Mccoy
Neurodevelopmental Alterations In A Rodent Model Of Temperamental Differences, Chelsea Mccoy Mccoy
All ETDs from UAB
Understanding biological mechanisms that shape brain development and susceptibility to emotional dysfunction is crucial for generating improved treatments for depression and anxiety disorders. To study neurodevelopmental factors that influence emotionality, we use model rats that were bred for distinct behavioral responses to novelty. Rats bred for low novelty response (LRs) exhibit a high anxiety-/depressive-like phenotype compared to high novelty responder rats (HRs), which vigorously explore novelty and exhibit high impulsivity, aggression, and risk-taking. Transcriptome profiling revealed multiple gene expression differences in the early postnatal hippocampus and amygdala and in the adult amygdala of HR/LR rats. Through gene ontology analysis, we …
Cell-Specific Pgc-1Α-Dependent Transcription: Implications For Cognitive And Motor Dysfunction, Laura Mcmeekin
Cell-Specific Pgc-1Α-Dependent Transcription: Implications For Cognitive And Motor Dysfunction, Laura Mcmeekin
All ETDs from UAB
Expression and/or function of transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is reduced in a variety of both neurodegenerative and psychiatric disorders. However, it is difficult to determine the significance of decreased PGC-1α expression and/or function in disease without knowing 1) the localization of these changes, 2) what the normal function of PGC-1α is in that specific cell-type, and 3) how its role in one neuronal population is different from its role in another. PGC-1α is highly expressed in GABAergic interneurons, and although it plays a significant role in interneuron function, several reports suggest that it also plays …
Neonatal Microbial Exposure And Its Effects On The B Cell Repertoire And Development Of Respiratory Allergies, Preeyam Patel
Neonatal Microbial Exposure And Its Effects On The B Cell Repertoire And Development Of Respiratory Allergies, Preeyam Patel
All ETDs from UAB
The incidence of asthma has increased dramatically among children living in developed countries, and the hygiene hypothesis suggests that this is the result of decreased neonatal exposure to microbes. Microbes and allergens can bear similar antibody-reactive epitopes, and exposure to microbes bearing these epitopes during early life can permanently alter the frequency and clonality of the antigen-specific B cell repertoire. The objective of this dissertation was to determine if B cells stimulated by microbes during early life could suppress the development of respiratory allergies during adult life. Both Streptococcus pneumoniae (pneumococcus) and house dust mite (HDM) express antibody-reactive phosphorylcholine (PC) …
Genome-Wide Transcription And Dna Methylation Profiling In An App Mouse Model Of Alzheimer’S Disease, Mikael C. Guzman Karlsson
Genome-Wide Transcription And Dna Methylation Profiling In An App Mouse Model Of Alzheimer’S Disease, Mikael C. Guzman Karlsson
All ETDs from UAB
The ability to encode information for long-term behavioral adaptation relies on experience-dependent alterations in neuronal plasticity. Neuronal plasticity encompasses the cellular and molecular changes that modulate synaptic communication between neurons as well as intrinsic electrophysiological properties within neurons. Epigenetic mechanisms, including DNA cytosine methylation and histone post-translational modifications, are powerful regulators of neuronal gene expression, allowing for dynamic, bidirectional regulation of transcriptional signatures necessary for neuronal plasticity. Emerging evidence using candidate-gene and microarray-based approaches suggest that the deficits in neuronal plasticity and cognitive impairment observed in Alzheimer’s disease (AD) is attributable, in part, to aberrant cytosine methylation and transcription of …
Behavioral And Developmental Abnormalities In Sult4a1 Deficient Zebrafish, Francis Crittenden
Behavioral And Developmental Abnormalities In Sult4a1 Deficient Zebrafish, Francis Crittenden
All ETDs from UAB
Since its identification in 2000, sulfotransferase (SULT) 4A1 has presented an enigma to the field of cytosolic SULT biology. SULT4A1 is exclusively expressed in neural tissue, is highly conserved, and has been identified in every vertebrate studied to date. Despite this singular level of conservation, no substrate or function for SULT4A1 has been identified. Previous studies demonstrated that SULT4A1 does not bind the obligate sulfate donor, 3’-phosphoadenosine-5’-phosphosulfate (PAPS), yet SULT4A1 is classified as a SULT superfamily member based on sequence and structural similarities to the other SULTs. In this study, RNA-seq was used to search for alterations in gene ex-pression …
Regulation Of Breast Cancer Metastasis By Sin3 Chromatin Remodeling Complexes, Monica Jeanene Lewis
Regulation Of Breast Cancer Metastasis By Sin3 Chromatin Remodeling Complexes, Monica Jeanene Lewis
All ETDs from UAB
Metastasis continues to be the most difficult clinical challenge for breast cancer. Survival rates for patients with metastatic breast cancer have not significantly changed in the past 20 years. Therefore, we need a better understanding of the molecular mechanisms that regulate breast cancer metastasis to develop effective therapies. SIN3 chromatin remodeling complexes have been implicated in breast cancer progression. Mammalian cells have two paralogs of SIN3 (SIN3A and SIN3B) that are encoded by distinct genes and have unique functions during development. However, specific roles for SIN3A and SIN3B in breast cancer progression have not been characterized. To better understand how …
Analysis Of The Ciliary Genes Gas8 And Mks6 Reveal Conserved Roles In Cilia Motility And Transition Zone Function, Wesley Robert Lewis
Analysis Of The Ciliary Genes Gas8 And Mks6 Reveal Conserved Roles In Cilia Motility And Transition Zone Function, Wesley Robert Lewis
All ETDs from UAB
Cilia are microtubule based cellular appendages that are present throughout the hierarchy of the animal kingdom. These appendages are utilized for a wide array of functions such as motility in single celled organisms to coordinating complex cellular signaling pathways in more complex organisms. Though these appendages are well conserved, the exact function of cilia in many cell types remains unknown. Recently, cilia are tied to a myriad of developmental diseases and diseases of adult homeostasis collectively referred to as ciliopathies. Dysfunction in cilia results in a wide array of phenotypes ranging from retinal degeneration to polydactyly, cystic kidney disease, and …
Role Of Autocrine And Paracrine Wnt Signaling In Chronic Myeloid Leukemia Stem Cells, Puneet Agarwal
Role Of Autocrine And Paracrine Wnt Signaling In Chronic Myeloid Leukemia Stem Cells, Puneet Agarwal
All ETDs from UAB
Treatment of chronic myeloid leukemia (CML) with BCR-ABL tyrosine kinase inhibitors (TKIs) fails to eradicate the leukemia stem cells (LSCs) from which the disease arises. Previously, we and others have shown that LSC persistence is related to kinase-independent mechanisms and mediated in part by signals from the bone marrow microenvironment (BMM). Specifically, we found that WNT signaling from the BMM may contribute to preservation of CML LSC following TKI treatment. Wnt secretion and activity requires their palmitoylation by the Porcupine acyltransferase (PORCN). WNT974 (formerly LGK974) is a potent PORCN inhibitor that blocks WNT signaling and demonstrates in vivo efficacy against …
Reorganization Of The Golgi Apparatus During Human Cytomegalovirus Infection, George Michael Rebmann
Reorganization Of The Golgi Apparatus During Human Cytomegalovirus Infection, George Michael Rebmann
All ETDs from UAB
Human cytomegalovirus (HCMV) is the largest and most structurally complex of all the herpesviruses. HCMV is an important human pathogen that results in significant morbidity and disease in immunocompromised individuals. The assembly of herpesviruses is complex and involves a nuclear and cytoplasmic phase. The nuclear events of capsid assembly and genome incorporation as well as nuclear egress are believed to be similar in all herpesviruses and as such, are more clearly defined then the cytoplasmic phase; including the process of tegument and envelope acquisition. Human Cytomegalovirus induces the reorganization of the cellular secretory pathway including the Golgi apparatus and membranes …
Structural Basis For Lipid-And Calmodulin-Mediated Akt Activation In Breast Cancer Cells, Constance Agamasu
Structural Basis For Lipid-And Calmodulin-Mediated Akt Activation In Breast Cancer Cells, Constance Agamasu
All ETDs from UAB
Growth and survival signals initiated at the cell surface by receptor-ligand interactions often involve a downstream activation of Akt, a serine/threonine kinase critical in regulating cell survival, apoptosis and oncogenesis. Hyper-activation of Akt is a common tumorigenic event, thereby making the Akt activation pathway a prime target for cancer therapy. The translocation of Akt to the plasma membrane (PM) for phosphorylation is a critical step in the Akt activation pathway. It has been established that membrane binding of Akt is mediated by direct interactions between its pleckstrin homology domain (PHD) and membrane lipid phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3]. There is now emerging …
Neurobiological Consequences Of Perinatal Ssri Exposure, Matthew Edward Glover
Neurobiological Consequences Of Perinatal Ssri Exposure, Matthew Edward Glover
All ETDs from UAB
Selective serotonin reuptake inhibitors (SSRIs) have been a mainstay pharmacological treatment for women experiencing depression during pregnancy and postpartum for nearly three decades. Recently, though, growing evidence indicates that early-life SSRI exposure triggers long-lasting behavioral abnormalities. Clinically, children exposed to SSRIs in early life exhibit increased internalizing behavior, reduced social behavior, and increased risk for depression in adolescence. Similarly, in rodents, perinatal SSRI exposure leads to increased traits of anxiety- and depression-like behavior. Interestingly, certain individuals are more susceptible to early-life SSRI exposure than others, suggesting that perinatal SSRI exposure poses greater risks for negative outcome within certain populations; however, …
Human Cytosolic Sulfotransferase (Sult) 1b1 Half-Site Reactivity And The Identification And Characterization Of A Novel Variant Sult1b1 Isoform (L145v), Zachary Evan Tibbs
Human Cytosolic Sulfotransferase (Sult) 1b1 Half-Site Reactivity And The Identification And Characterization Of A Novel Variant Sult1b1 Isoform (L145v), Zachary Evan Tibbs
All ETDs from UAB
The human cytosolic sulfotransferases (hSULTs) are a fourteen-member family of phase II drug-metabolizing enzymes that catalyze the transfer of a sulfonate moiety from 3’-phosphoadenosine 5’-phosphosulfate (PAPS) to a recipient substrate. SULT-mediated sulfation serves to deactivate physiological hormones and detoxify xenobiotics. SULT1B1 is primarily resident to the gastrointestinal tract, liver, and possibly peripheral white blood cells (WBCs), whereby it performs its supposed physiological role. The iso-form has the capacity to sulfate thyroid hormones, small phenols, and polyaromatic hy-drocarbons resulting in their inactivation, detoxification, and bioactivation/detoxification, respectively. Immunohistochemistry was used to show hSULT1B1 protein is present in periph-eral lymphocytes and neutrophils. Further, …
Interplay Between Her2, Parp1, And Nf-Κb In Breast Cancer: Potential Therapeutic Implications, Monicka Ewa Wielgos
Interplay Between Her2, Parp1, And Nf-Κb In Breast Cancer: Potential Therapeutic Implications, Monicka Ewa Wielgos
All ETDs from UAB
We previously reported that HER2+ breast cancers are susceptible to Poly (ADP-Ribose) polymerase inhibitors (PARPi) alone, agents that are efficacious against homologous recombination (HR) deficient tumors. However, this phenomenon was determined to be independent of a HR repair deficiency but rather due to suppression of NF-κB activity and signaling by PARP inhibition. Further, HER2 overexpression itself was necessary and sufficient to confer this susceptibility. Interestingly, PARP1 and phosphorylated RelA/p65 (NF-κB) levels were found to be elevated in human HER2+ breast cancers compared to luminal breast cancers. These data suggest a possible interplay between HER2, PARP1, and NF-κB, and how this …
The Impact Of Rrna And Trna Synthesis On Chromatin Structure And Cell Fate, Jessica Makofske Woolnough
The Impact Of Rrna And Trna Synthesis On Chromatin Structure And Cell Fate, Jessica Makofske Woolnough
All ETDs from UAB
The Central Dogma of molecular biology describes the process by which genetic material is faithfully converted into functional molecules across all domains of life. Originally, RNA was solely understood as an intermediate in this process. However, mounting evidence over the past 50 years has made clear that RNA have diverse functional roles as a class of molecule termed non-coding RNA. Two of the first described non-coding RNA have essential roles within the Central Dogma, itself: ribosomal RNA (rRNA) and transfer RNA (tRNA). These two non-coding RNA are highly abundant, collectively accounting for up to 90% of the total transcript in …
What's Up, Dut? Help, Help I'M Being Derepressed; The Great Derepression Of Sapis Or How I Learned To Stop Worrying And Love Mobilization, Rosanne Lorin Lee Hill
What's Up, Dut? Help, Help I'M Being Derepressed; The Great Derepression Of Sapis Or How I Learned To Stop Worrying And Love Mobilization, Rosanne Lorin Lee Hill
All ETDs from UAB
Staphylococcus aureus is known to cause disease in both human and animal populations. Many of the virulence factors important for S. aureus pathogenesis are found on mobile genetic elements known as S. aureus pathogenicity islands (SaPIs). SaPIs can transduce into surrounding cells, giving those cells the ability to produce virulence factors. Derepression allows SaPIs to be excised from S. aureus genome to initiate mobilization. Derepressors have been identified for multiple SaPIs, but it remains unknown if the same SaPI can be derepressed by multiple derepressors. It has been shown that SaPIbov1 can be derepressed by the type 1 dUTPase from …
Structure-Function Relationships In The Sec7 Guanine Nucleotide Exchange Factor Gbf1, Jay Manoj Bhatt
Structure-Function Relationships In The Sec7 Guanine Nucleotide Exchange Factor Gbf1, Jay Manoj Bhatt
All ETDs from UAB
All eukaryotic cells contain a secretory pathway composed of membrane-bound compartments connected by vesicles that transport cargo from the endoplasmic reticulum (ER) through the Golgi apparatus to various destination within and outside the cell. The Golgi Brefeldin A-resistant Factor 1 (GBF1) is required for protein traffic between ER and Golgi and within the Golgi. GBF1 belongs to a family of Guanine nucleotide Exchange Factors (GEFs) that stimulate the nucleotide exchange of GDP for GTP on small GTPases called ADP-ribosylation factors (ARFs). Once GTP-bound, ARFs become active and initiate a cascade of events that lead to vesicle formation. Thus, GBF1 is …
Regulation Of Vibrio Cholerae Biofilm Formation By H-Ns Repression And Anti-Repression, Julio Cesar Ayala-Figueredo
Regulation Of Vibrio Cholerae Biofilm Formation By H-Ns Repression And Anti-Repression, Julio Cesar Ayala-Figueredo
All ETDs from UAB
The diarrheal disease cholera is caused by the Gram-negative and motile bacterium Vibrio cholerae of serogroups O1 and O139. V. cholerae can switch between planktonic (motile) and sessile (biofilm) lifestyles. Biofilms are sessile communities encased in a self-produced extracellular matrix mainly composed of exopolysaccharide, proteins and extracellular DNA. Biofilm formation enhances the capacity of V. cholerae to persist in environmental waters and increases its infectivity. The bacterial second messenger cyclic diguanylic acid (c-di-GMP) regulates the transition between motile and biofilm lifestyles in V. cholerae. At low cell density, two c-di-GMP receptors, the LuxR-type regulator VpsT and the NtrC-type regulator VpsR …
Fcrl5 Counter-Regulates Natural And T Cell-Independent Immunoglobulin Production By Innate-Like B Cells, Eugene John Becker
Fcrl5 Counter-Regulates Natural And T Cell-Independent Immunoglobulin Production By Innate-Like B Cells, Eugene John Becker
All ETDs from UAB
At homeostasis and during the initial phases of primary responses to pathogens, humoral host defense is chiefly coordinated by specialized B cells known as splenic marginal zone (MZ) and body cavity-derived B-1 B cells. These front line immune mediators are termed “innate like” due to their ability to secrete broadly-reactive natural antibodies and respond rapidly to antigens in a T cell-independent manner. The production of natural antibodies possessing specificities for self-antigens allows clearance of cellular debris, maintenance of homeostasis and protection from infections that can also predispose the host to immunological disease. However, how the functions of these specialized cells …
Transcriptional Regulation Of Interleukin 10 In Cd4+ T Cells, Carson Edward Moseley
Transcriptional Regulation Of Interleukin 10 In Cd4+ T Cells, Carson Edward Moseley
All ETDs from UAB
Autoimmune and autoinflammatory diseases are a collection of disorders that are mediated by reaction of the adaptive immune system against self or commensal antigens. Altered transcription of genes involved in T cell activation and function is a key mediator of predisposition to numerous autoimmune disorders, including Inflammatory Bowel Disease (IBD) and Multiple Sclerosis (MS). However, we have an inadequate understanding of how the transcriptional circuits controlling these genes are dysregulated in disease. Interleukin-10 (IL-10) is cytokine with potent anti-inflammatory activity that is critical for restraining immune-mediated pathology to self-tissues. Notably, patients with nullifying mutations in IL10 develop a severe IBD …
The Role Of Mammalian Tribbles Homolog 3 (Trb3) In Macrophage Biology; Evidence For Reciprocal Regulation Of Macrophage Function In Foam Cell Formation, Dennis Steverson
The Role Of Mammalian Tribbles Homolog 3 (Trb3) In Macrophage Biology; Evidence For Reciprocal Regulation Of Macrophage Function In Foam Cell Formation, Dennis Steverson
All ETDs from UAB
Atherosclerosis is disease characterized by dysregulated lipid metabolism and chronic inflammation. Macrophages are critical to the progression of the disease and are involved in the pathophysiology at all stages of the disease. In the early stages, macrophages are responsible for fatty streak formation by becoming foam cells through lipid uptake. In the later stages, macrophages contribute to the degradation of the fibrous cap and are largely responsible for chronic inflammation in atherosclerotic plaques. Tribbles homolog 3 (TRB3) is a pseudokinase that inhibits Akt activation by blocking its phosphorylation site. TRB3 is expressed on numerous cell types in the body (pancreatic …
Polycomb Repressive Complex 2 And Heterochromatin Protein 1 Beta Regulate Neural And Neural Crest Development, Chih-Liang Tien
Polycomb Repressive Complex 2 And Heterochromatin Protein 1 Beta Regulate Neural And Neural Crest Development, Chih-Liang Tien
All ETDs from UAB
Epigenetic factors control gene expression via modulating chromatin conformation. Current studies on epigenetics mainly focus on biochemical mechanisms or functions of epigenetic factors in cancer or neurobiology. The underlying mechanism for epigenetic regulation in early embryonic development, particularly neural and neural crest development, is not well understood. In this thesis, the model organism, Xenopus laevis, is used to study epigenetic factors – polycomb repressive complex 2 (PRC2) and heterochromatin protein 1 beta (HP1β) in neural and neural crest development. In chapter one, the processes of neural and neural crest development are described, and the concepts of epigenetic mechanisms, such as …
Cell Signaling Pathways As Targets For Precision Medicine In Head And Neck Squamous Cell Carcinoma, Alice Weaver
Cell Signaling Pathways As Targets For Precision Medicine In Head And Neck Squamous Cell Carcinoma, Alice Weaver
All ETDs from UAB
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with high rates of recurrence and mortality. Unlike other cancer types, genome sequencing studies have failed to produce clinically actionable targets to improve HNSCC management. Therefore, alternative methods are needed to study the molecular mechanisms responsible for disease progression and response to therapy. The focus of this research was to determine how dysregulation of cell signaling pathways affects outcomes in HNSCC. In HPV-positive HNSCCs, we hypothesized that HPV induces dysregulation of the DNA damage response which mediates differences in therapeutic sensitivity and survival. We identified a defect in DNA …
Microglia Orchestrate The Inflammatory Response To Alpha-Synuclein In Parkinson Disease Models, Aaron Thome
Microglia Orchestrate The Inflammatory Response To Alpha-Synuclein In Parkinson Disease Models, Aaron Thome
All ETDs from UAB
Parkinson disease (PD) is the most common neurodegenerative movement disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and widespread aggregates of the protein alpha-synuclein (α-syn). Increasing evidence points to inflammation as a chief mediator of PD with many of the inflammatory manifestations of human PD cases recapitulated in animal models of PD. We began by examining the inflammatory potential of α-syn fibrils, a newly characterized α-syn conformation that is neurotoxic and prion-like in its endogenous α-syn recruitment and cellular transmission. Our studies provide evidence that the α-syn fibrils evoke a pro-inflammatory response …
The Effect Of Proinflammatory Cytokines On Thioredoxin-Interacting Protein In Pancreatic Beta-Cells, Kyunghee Hong
The Effect Of Proinflammatory Cytokines On Thioredoxin-Interacting Protein In Pancreatic Beta-Cells, Kyunghee Hong
All ETDs from UAB
Pro-inflammatory cytokines, such as Interleukin (IL)-1β, Tumor necrosis factors (TNF) α, and Interferon (IFN)γ, have been implicated as critical mediators of β-cell destruction in diabetes. In addition, although a combination of these three cytokines has been used to mimic the inflammatory conditions of type 1 diabetes in vitro, the mechanisms underlying the effect are not fully understood. Previously, we discovered Thioredoxin-interacting protein (TXNIP) as a key regulator of glucotoxicity-induced β-cell apoptosis and β-cell dysfunction, while deletion of TXNIP prevented type 1 (T1D) and type 2 diabetes (T2D). However, the effects of proinflammatory cytokines on the regulation of TXNIP have not …
The Matricellular Protein Ccn1 Potentiates Fibrogenic Responses To Lung Injury, Ashish Kurundkar
The Matricellular Protein Ccn1 Potentiates Fibrogenic Responses To Lung Injury, Ashish Kurundkar
All ETDs from UAB
Normal wound healing is a well-coordinated reparative response to injury aimed at restoring the normal tissue function. The dynamic interactions between cells and ex-tracellular matrix (ECM) regulate and dictate the fate of tissue repair process. Fibrosis is a dysregulated wound healing with excessive deposition of ECM and loss of tissue func-tion. Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic disease of lung with no cure. Matricellular proteins are non-structural matrix proteins which regulates the cellular functions by directly binding to cell surface integrins and/or indirectly modulating growth factor signaling. Matricellular proteins are emerging as critical mediators of tissue injury …
The Role Of Hydrogen Peroxide In The Modulation Of Capsule Biosynthesis In Streptococcus Pneumoniae Serotype 2, Jocelyn Renee Hauser
The Role Of Hydrogen Peroxide In The Modulation Of Capsule Biosynthesis In Streptococcus Pneumoniae Serotype 2, Jocelyn Renee Hauser
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Streptococcus pneumoniae is a gram-positive bacterial pathogen that causes diseases such as pneumonia, meningitis, bacteremia and middle ear infections. The major virulence factor of S. pneumoniae is its polysaccharide capsule. The capsule enables the organism to evade host defenses by providing protection against complement-mediated opsonophagocytosis in systemic sites and by allowing the organism to successfully colonize the nasopharynx. The nasopharynx is the natural reservoir of S. pneumoniae. In the nasopharynx, S. pneumoniae is in a high oxygen (O2) environment, however when it has the opportunity to bypass host defenses and invade systemic sites, it reaches environments with low O2. Capsule …
Targeting The Tumor-Promoting Microenvironment With Inhibitors Of Pro-Hgf Activation, Benjamin Yaw Owusu
Targeting The Tumor-Promoting Microenvironment With Inhibitors Of Pro-Hgf Activation, Benjamin Yaw Owusu
All ETDs from UAB
The tumor microenvironment plays a key role in tumor progression and therapeutic resistance. Hepatocyte growth factor (HGF), commonly expressed by cancer-associated fibroblasts, mediates signaling via its receptor, MET, and promotes survival, proliferation, migration and invasion of cancer cells. In addition, HGF dependence has emerged as a hallmark of therapeutic resistance. HGF is secreted as an inactive precursor, pro-HGF, which requires proteolytic cleavage and processing to form the mature, active HGF. This is the rate-limiting step in the HGF/MET signaling pathway and it is achieved by one of the serine proteases, matriptase, hepsin and HGF activator (HGFA). At Southern Research, we …
The Function Of Prmt1 In Normal And Abnormal Megakaryopoiesis, Hairui Su
The Function Of Prmt1 In Normal And Abnormal Megakaryopoiesis, Hairui Su
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Protein arginine methylation is a common type of post-translational modifications. Protein arginine methyltransferase 1 (PRMT1) is the predominant PRMT that is involved in diverse physiological and pathological processes in mammalian cells. Dysregulation of PRMT1 is often positively correlated with cancer development, yet many aspects of PRMT1’s role in cancer, especially in acute megakaryoblastic leukemia (AMKL) remain unclear. We identified two PRMT1-methylated substrates and how they impact normal and abnormal megakaryopoiesis. In this dissertation, we demonstrate that dual-specificity protein phosphatase 4 (DUSP4) and RNA binding motif protein 15 (RBM15), two crucial factors for megakaryocytic (MK) differentiation, are methylated by PRMT1 and …
The Role Of Glutamate In Immune Cell Infiltration And Excitotoxic Mechanisms In Autoimmune Demyelination, Kirsten Scarlett Evonuk
The Role Of Glutamate In Immune Cell Infiltration And Excitotoxic Mechanisms In Autoimmune Demyelination, Kirsten Scarlett Evonuk
All ETDs from UAB
Multiple sclerosis is the most common neurological disorder in young adults. Current treatments modulate the immune system, but no treatments prevent central nervous system damage. Inflammation occurs even during disease remission, contributing to ongoing damage and resulting in disease progression. The lack of neuroprotective treatments despite continued inflammatory onslaught in the central nervous system indicates the need for therapeutic discovery in this area. One potential therapeutic target is glutamate, whose dysregulation in multiple sclerosis has been implicated in excitotoxic cellular death. Herein we describe the roles of glutamate in multiple sclerosis and explore the blockade of a source of excitotoxic …