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Mechanisms By Which Tra-8 Anti-Dr5 Antibody And Chemotherapy Enhance Cytotoxicity In Breast Cancer, Hope M. Amm Jan 2010

Mechanisms By Which Tra-8 Anti-Dr5 Antibody And Chemotherapy Enhance Cytotoxicity In Breast Cancer, Hope M. Amm

All ETDs from UAB

Breast cancer is the second leading cause of cancer-related death in American women and metastatic breast cancer has a 5-year survival rate of only 26%. Current targeted treatments for this disease include anti-estrogen strategies for estrogen receptor positive tumors (~60%) and anti-Her2/Neu strategies for tumors overexpressing this receptor (20-25%). A percentage of breast cancer patients, however, are resistant to these therapies and are left without any effective treatment options. One of the agents currently being investigated to improve breast cancer survival is TRA-8, an agonistic monoclonal antibody to death receptor 5 (DR5), which induces apoptosis in various types of cancer …


Identification And Validation Of Biodosimetry Markers In Multiple Models Of Radiation Exposure, Ashley Nicole Filiano Jan 2010

Identification And Validation Of Biodosimetry Markers In Multiple Models Of Radiation Exposure, Ashley Nicole Filiano

All ETDs from UAB

Following a radiological or nuclear disaster, radiation dose assessment is imperative to minimize morbidity and mortality through rationally directed medical intervention. Current methods of retrospective dosimetry are not amenable to mass exposure scenarios and remain limited to monitoring of clinical symptoms (nausea/vomiting and lymphocyte depletion) and cytogenetic analysis. The goal of this study was to identify radiation biomarkers capable of qualitative (non-irradiated/irradiated) and quantitative (dose) assessment of radiation exposure. Initial analyses revealed 17 radiation-responsive cytokine/chemokine genes in blood samples from 6 pediatric cancer patients undergoing fractionated total body irradiation (TBI). These 17 genes were combined with 29 additional IR-inducible genes …


Dna Replication And Cytokinesis In Drosophila Melanogaster, Anton Svitin Jan 2010

Dna Replication And Cytokinesis In Drosophila Melanogaster, Anton Svitin

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DNA replication and cytokinesis are two important parts of the cell division process. Our studies address different aspects of both of these processes and potential links between them. One of the best approaches for studying DNA replication in eukaryotes has been an analysis in cell free in vitro systems. The existing cell free replication systems for Drosophila are relatively ineffective. In the first part of this work, we have developed an optimized in vitro system to study DNA replication using early egg extracts of Drosophila. Our studies indicate that this system proves to be an extremely useful tool for a …


Pneumococcal Vaccine Response And Aging In Human, Saeyoung Park Jan 2010

Pneumococcal Vaccine Response And Aging In Human, Saeyoung Park

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Streptococcus pneumoniae is a major human pathogen, especially for young children and older adults. To protect from pneumococcal diseases, 23-valent pneumococcal polysaccharide vaccine (PPV23) has been used clinically since 1983. However, PPV23 is not so effective among old adults with its protective efficacy diminishing with age. We confirmed that young and old adults, who were immunized with PPV23, have comparable pneumococcal polysaccharide (PS) specific IgG levels. Interestingly, we found that old adults had lower IgA and IgM antibody levels than young adults for three serotypes (serotype 14, 18C and 23F). Consistent with the previous results, opsonic capacities of immune sera …


The Role Of Map Kinase Cascade In Msp Signaling Response, Youfeng Yang Jan 2010

The Role Of Map Kinase Cascade In Msp Signaling Response, Youfeng Yang

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The MSP domain is an evolutionarily conserved immunoglobulin-like structure of about 120 amino acids (Miller et al., 2001). A P56S missense mutation in the MSP domain of the human vapb gene is associated with a dominantly inherited form of Amyotropic Lateral Sclerosis (ALS) or Spinal Muscular Atrophy (SMA) (Nishimura et al., 2004). In C. elegans, secreted MSP binds to the VAB-1 Eph receptor and other receptors on oocyte and ovarian sheath cell surfaces (Miller et al., 2003). We have recently shown that the P56S mutation prevents secretion of the VAPB MSP domain, suggesting that the signaling function is important in …


Cellular Mechanisms Involved In Host Responses To Porphyromonas Gingivalis And Its Virulence Factor Hemagglutinin B, Dalia Emil Gaddis Jan 2010

Cellular Mechanisms Involved In Host Responses To Porphyromonas Gingivalis And Its Virulence Factor Hemagglutinin B, Dalia Emil Gaddis

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Porphyromonas gingivalis is a main causative agent for adult chronic periodontitis and immunization with its virulence factor Hemagglutinin B (HagB) provides protection against infection. Toll-like receptors (TLRs) recognize various microbial products and are crucial in eliciting and regulating the innate and adaptive immune responses to infections. The objective of this dissertation was to investigate the cellular mechanisms that influence the innate and adaptive immune response to HagB and P. gingivalis, focusing on the role of TLR signaling in the response. We started with investigating the ability of HagB to activate dendritic cells (DC), the most efficient antigen-presenting cell in priming …


Lens Cataract: Biochemical Analysis Of The Alpha Crystallins, David Ray Stella Jan 2010

Lens Cataract: Biochemical Analysis Of The Alpha Crystallins, David Ray Stella

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The cataract is a common ailment affecting the aged population. It appears over time and affects the quality of one’s life by the eventual loss of vision. Currently, there is no effective strategy to prevent or treatment to reverse the development of a cataract. As well, there is no consensus on one particular mechanism or sequence of events that contributes to its formation. In order to better understand the possible etiology of the cataract, it is necessary to define the biochemical changes that occur to lens proteins as one ages, as these are the key players in the prevention of …


Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer, Heather Nicole Tinsley Jan 2010

Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer, Heather Nicole Tinsley

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Breast cancer remains a major health concern, despite efforts to develop improved therapeutics. Chemoprevention is a promising strategy for reducing breast cancer-related morbidity and mortality. However, with the exception of the selective estrogen receptor modulators (SERMs), which have limited efficacy and severe toxicities, no drugs have been approved for breast cancer chemoprevention. Studies demonstrate that certain nonsteroidal anti-inflammatory drugs (NSAIDs) display promising chemopreventive efficacy. Unfortunately, the depletion of physiologically important prostaglandins due to inhibition of the cyclooxygenase (COX) enzymes results in potentially fatal toxicities, which exclude the use of NSAIDs and COX-2 selective inhibitors for chemoprevention. Ample data, however, suggest …


Il-21 Dictates The Quality Of The Cd8 T Cell Response During Acute And Chronic Infections, John Seung-Hoon Yi Jan 2010

Il-21 Dictates The Quality Of The Cd8 T Cell Response During Acute And Chronic Infections, John Seung-Hoon Yi

All ETDs from UAB

CD8 T cells contribute to the control of intracellular pathogens including viruses and certain bacteria. Recognition of foreign antigens by antigen-specific CD8 T cells initiates a differentiation process by which CD8 T cells gain effector functions including the ability to rapidly produce cytokines and kill infected cells. Currently, it is not well understood what signals dictate the generation of robust CD8 T cell responses, however it has been demonstrated that without CD4 T cell help CD8 T cell responses are compromised. CD4 T cells are the primary producers of interleukin-21 (IL-21), which has broad immunological actions. Thus for this dissertation, …


O-Glcnac Transferase Modulates Jnk1 And Foxo4 Transcription Factor To Resist Acute Oxidative Stress, Shiuh-Rong Ho Jan 2010

O-Glcnac Transferase Modulates Jnk1 And Foxo4 Transcription Factor To Resist Acute Oxidative Stress, Shiuh-Rong Ho

All ETDs from UAB

O-GlcNAcylation is an abundant and dynamic post-translational modification on serine and threonine residues of nuclear and cytoplasmic proteins. O-GlcNAc Transferase (OGT) and Nuclear Cytoplasmic O-GlcNAcase and Acetyltransferase (NCOAT) are the only two enzymes and major regulators in this process. In the past two decades, many studies have demonstrated its important modulation roles in nutrient sensing, protein turnover, cell cycle progression, transcription, translation as well as stress resistance. Among these biological functions, the understanding of O-GlcNAcylation dependent oxidative stress is relatively unknown. This study aims to examine the effects of O-GlcNAcylation on JNK1 and FOXO4 transcription factors under acute oxidative stress …


Hpv Dna Partitioning During Mitosis As Followed By Fluorescence Microscopy, Robert J. Carter Jan 2010

Hpv Dna Partitioning During Mitosis As Followed By Fluorescence Microscopy, Robert J. Carter

All ETDs from UAB

Human papillomaviruses (HPVs) are small, double-stranded deoxyribonucleic acid (DNA) tumor viruses capable of establishing persistent infections in the epithelia. After infecting actively-dividing basal cells, the papillomavirus (PV) genome is main-tained as extrachromosomal nuclear plasmids. It is largely unknown how the viral ge-nome is maintained in actively-dividing cells. Our lab demonstrated that several HPV genotypes appear to employ a distinct strategy to facilitate partitioning of HPV DNA into daughter cells during mitosis. Association of the HPV-11 origin of replication (ori)-binding protein E2 with the mitotic apparatus via cellular adapter proteins is thought to mediate equal partitioning of HPV genomes into daughter …


Role Of Epithelial Sodium Channel And Acid Sensing Ion Channel In Glioblastoma Multiforme, Niren Kapoor Jan 2010

Role Of Epithelial Sodium Channel And Acid Sensing Ion Channel In Glioblastoma Multiforme, Niren Kapoor

All ETDs from UAB

Glioblastoma Multifrome is the most common and aggressive of the primary brain tumors. These tumors express multiple members of the Epithelial Sodium Channel (ENaC)/Degenerin (Deg) family, associated with a basally active amiloride sensitive cation current. We hypothesize that this glioma current is mediated by a hybrid channel composed of a mixture of Epithelial Sodium Channel (ENaC) and Acid Sensing Ion Channel (ASIC) subunits. To test this hypothesis we made dominant negative cDNAs for ASIC1, αENaC, and γENaC. D54-MG glioma cells transfected with the dominant negative constructs for ASIC1, αENaC, or γENaC showed reduced protein expression for each of the specific …


Role Of Transient Receptor Potential Canonical Channels In Glioma Cell Biology, Valerie Christine Bomben Jan 2010

Role Of Transient Receptor Potential Canonical Channels In Glioma Cell Biology, Valerie Christine Bomben

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ROLE OF TRANSIENT RECEPTOR POTENTIAL CANONICAL CHANNELS IN GLIOMA CELL BIOLOGY VALERIE C. BOMBEN DEPARTMENT OF NEUROBIOLOGY ABSTRACT Gliomas, primary brain tumors derived from glial cells, constitute the majority of malignant tumors within the central nervous system. The most malignant of these tumors, grade IV Glioblastoma multiforme, are characterized by extensive proliferation, cellular and nuclear atypia, angiogenesis, areas of necrosis, and widespread invasion into the brain parenchyma. Data from our lab and others have implicated ion channels in the invasion and proliferation of glioma cells. Moreover, calcium signaling in gliomas and other cells has been implicated in both migration and …


The Role Of Socs Proteins In Hiv Immune Evasion, Lisa Nowoslawski Akhtar Jan 2010

The Role Of Socs Proteins In Hiv Immune Evasion, Lisa Nowoslawski Akhtar

All ETDs from UAB

Upon human immunodeficiency virus (HIV) infection the host mounts a robust and multifaceted immune response. To achieve successful replication, HIV must possess a powerful arsenal of immune evasion weapons. While a complex strategy for HIV immune evasion has been described in the periphery, little is known about the mechanism allowing HIV to overcome the simple interferon (IFN)-ß-mediated innate immune defenses of the central nervous system (CNS). In light of the devastating cognitive dysfunction that is caused by HIV replication within the CNS, a better understanding of this mechanism is critical. Recent studies have shown that viral pathogens can induce the …


The Role Of Gli1 In Eralpha-Negative Breast Cancer: Promoting Survival, Migration, Invasion, And Metastasis, Yeon-Jin Kwon Jan 2010

The Role Of Gli1 In Eralpha-Negative Breast Cancer: Promoting Survival, Migration, Invasion, And Metastasis, Yeon-Jin Kwon

All ETDs from UAB

Glioma-associated oncogene homolog 1 (Gli1) is a well-known oncogene and a transcription factor that mediates several signaling pathways important for tumor progression, such as hedgehog, TGFß, Ras, and EGFR. Although Gli1 is known to play an important role in cancers of brain, skin, prostate, and the pancreas, the role of Gli1 in breast cancer was not previously well-defined. Therefore, this dissertation focuses on defining the role of Gli1 and the mechanism underlying Gli1-mediated transcription in breast cancer. Interestingly, the major findings of the dissertation clearly indicate that Gli1 promotes cell survival and is predictive of a poor outcome in Estrogen …


The Role Of Usp14 In Regulating Synaptic Development And Function Of The Neuromuscular Junctions, Ping-Chung Chen Jan 2010

The Role Of Usp14 In Regulating Synaptic Development And Function Of The Neuromuscular Junctions, Ping-Chung Chen

All ETDs from UAB

The ubiquitin proteasome system (UPS) plays critical roles in regulating multiple cellular functions, including protein abundance, trafficking, and cell signaling. In the nervous system, the UPS has been implicated in controlling a wide diversity of cellular process such as synaptic transmission, axon outgrowth, axon targeting, and synapse development. Although impairment of the UPS is observed in both neurodegenerative and developmental diseases, the mechanisms underlying how UPS dysregulation contributes to disease pathogenesis are not known. The proteasome, an approximate 2.5 megadaltons protein complex composed of 19S and 20S assemblies, is the site of ubiquitin-dependent protein degradation. Recent studies have demonstrated dysfunction …


The Role Of Fc Receptor-Like 2 In B Cell Signaling, Tanisha Anne Jackson Jan 2010

The Role Of Fc Receptor-Like 2 In B Cell Signaling, Tanisha Anne Jackson

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Fc receptor-like 2 (FCRL2) is a transmembrane protein with immunomodulatory potential that is preferentially expressed by memory B cells in humans. It has two consensus immunoreceptor tyrosine-based inhibitory motifs (ITIM) in addition to a putative immunoreceptor tyrosine-based activation motif (ITAM) sequence in its cytoplasmic domain. We have confirmed the cellular distribution of FCRL2 and ana-lyzed its functional potential to show that coligation with the B cell receptor (BCR) leads to tyrosine phosphorylation of its ITIM motifs and subsequent SHP-1 recruitment to facilitate inhibition of BCR signaling. Mutational analysis indicates that the tyrosine residues in both inhibitory motifs of FCRL2 are …


Regulation Of Vascular Smooth Muscle Cell Signaling And Metabolism By Platelet-Derived Growth Factor, Jessica Perez Jan 2010

Regulation Of Vascular Smooth Muscle Cell Signaling And Metabolism By Platelet-Derived Growth Factor, Jessica Perez

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Growth factors are important inducers of vascular cell growth whose regulation is altered during the pathogenesis of atherosclerosis. An increase in growth factor and cytokine production, as well as lipid oxidation is observed in cardiovascular disease (CVD) and contributes to altered vascular cell signaling, exacerbated atherosclerotic lesions and heart failure. A change in cellular bioenergetic status due to mitochondrial dysfunction or damage has also been noted in CVD. In this thesis, we first examine cell signaling pathways in vascular smooth muscle cells (VSMC) which are activated in response to platelet-derived growth factor (PDGF) and regulate the cell cycle protein changes …


Preclinical Pharmacology Of Novel Synthetic Iminoquinones As Anticancer Agents, Scharri Ezell Jan 2010

Preclinical Pharmacology Of Novel Synthetic Iminoquinones As Anticancer Agents, Scharri Ezell

All ETDs from UAB

Prostate cancer is the most common male malignancy and the second leading cause of cancer related death in the United States. Despite recent advances in the detection, diagnosis, and treatment of prostate cancer, there is a need for more effective therapies. Unfortunately, most conventional therapeutic modalities, such as androgen ablation therapy, frequently result in androgen-independent cancers. These cancers are typically more aggressive, metastatic, and resistant to chemotherapeutic agents than androgen-dependent prostate cancer. Therefore, agents that are effective against both androgen-sensitive and androgen-independent, as well as genetically diverse cancers are critically needed. The objective of the dissertation research was to address …


Red Blood Cell And Hemoglobin Dependent Modulation Of Reactive Species Metabolism: Implications For Vascular Homeostasis, Dario A. Vitturi Jan 2010

Red Blood Cell And Hemoglobin Dependent Modulation Of Reactive Species Metabolism: Implications For Vascular Homeostasis, Dario A. Vitturi

All ETDs from UAB

The recent discovery that red blood cells might mediate hypoxic blood flow together with accumulating evidence that suggests a role for the modulation of vascular inflammation has reshaped the way we think about the function of these cells. In this thesis we investigate the mechanisms that regulate these newly appreciated functions and focus on i) the ability of red cells to couple oxygen sensing with nitrite reduction and nitric oxide formation and ii) the role of the beta93cys, a conserved residue amongst mammalian hemoglobins and whose function remains unclear. Data will be presented that demonstrate that nitrite reduction to nitric …


A Nucleolar Specificity Factor For E2f1 Induced Cell Death, Jason Chang Paik Jan 2010

A Nucleolar Specificity Factor For E2f1 Induced Cell Death, Jason Chang Paik

All ETDs from UAB

The E2F family of transcription factors are important regulators of cell proliferation, and are often dysregulated in cancers. One member of the E2F family, E2F1, also has the ability to induce apoptosis; therefore, uncovering how E2F1-induced apoptosis is controlled is of interest in understanding tumorigenesis. To this end, we identified RRP1B as a novel target specifically induced by E2F1. RRP1B expression is specifically upregulated by E2F1 overexpression, but not other E2F family members. RRP1B expression is correlated with E2F1 expression during the cell cycle, and is significantly induced after DNA damage. The minimal RRP1B promoter region responsive to E2F1 was …


Evolution Of Pneumococcal Serogroup 6, Preston Eugene Bratcher Jan 2010

Evolution Of Pneumococcal Serogroup 6, Preston Eugene Bratcher

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Serogroup 6 of Streptococcus pneumoniae has been known to contain three serotypes, named 6A, 6B and 6C, with highly homologous capsule gene loci. The 6A and 6B capsule gene loci consistently differ from each other by only one nucleotide in the wciP gene. The 6A capsule gene locus has a galactosyltransferase (wciNα), which has been replaced with a glucosyltransferase (wciNß) in the 6C capsule gene locus. We considered that a new serotype, 6D, would be possible if the glucosyltransferase found in 6C strains was combined with the wciP gene from a 6B strain. We demonstrate that this gene combination yields …


The Effects Of Environmental Ozone Exposure On Vascular Function, Oxidative Stress, And Atherosclerosis, Gin Chuang Jan 2010

The Effects Of Environmental Ozone Exposure On Vascular Function, Oxidative Stress, And Atherosclerosis, Gin Chuang

All ETDs from UAB

Exposure to air pollutants are known to induce airway inflammation, decrease lung function, and worsen existing pulmonary conditions such as asthma. Additionally, air pollutant exposure has also been shown to impact cardiovascular health. Although these pollutant-induced cardiovascular effects were considered to be mediated by the direct action of pollutants upon the cardiovascular tissue and/or the indirect release of pro-inflammatory factors into the circulation, the relative contribution of the two pathways remained equivocal. Recently, several epidemiology studies associated ozone exposure with cardiovascular mortalities. However, relatively few studies to date have examined ozone in this context. In order to address our hypothesis …


Mechanisms Of Major Outer Membrane Protein (Momp)-Vaccine Induced Protective Immunity Against Chlamydia Muridarum Genital Infection, Christina M. Farris Jan 2010

Mechanisms Of Major Outer Membrane Protein (Momp)-Vaccine Induced Protective Immunity Against Chlamydia Muridarum Genital Infection, Christina M. Farris

All ETDs from UAB

Urogenital infection with Chlamydia trachomatis is the most common bacterial sexually transmit-ted disease with an estimated 90 million new infections occurring each year worldwide. In women infection with C. trachomatis can result in serious complications including ectopic pregnancy, pelvic inflammatory disease and tubal factor infertility. Despite very effective antimicrobial chemotherapy, control of the infection will likely require an effective vaccine. We have assessed the protective effect of an outer membrane based vaccine using a murine model of chlamydial genital tract infection. Female mice were vaccinated with C. muridarum major outer membrane protein (MOMP) plus the immunostimulatory adjuvants CpG-1826 and Montanide …


The Contribution Of Different Mechanisms Of Viral Sequence Variation To The Evolution Of Positive-Sense Single-Stranded Rna Viruses, Brett Earl Pickett Jan 2010

The Contribution Of Different Mechanisms Of Viral Sequence Variation To The Evolution Of Positive-Sense Single-Stranded Rna Viruses, Brett Earl Pickett

All ETDs from UAB

The Flaviviridae family of positive-sense single-stranded RNA (+ssRNA) viruses includes viral taxa which greatly impact public health worldwide. To explore how the viruses within the Flaviviridae family evolve, we examined the extent to which these viral taxa use nucleotide covariance, spontaneous mutation, and/or homologous recombination to vary their genotype as well as the resulting phenotype. We developed and used CovarView to assist us in simultaneously viewing and inspecting the results from whole genome covariance analyses. This resulted in the identification of previously-characterized RNA functional structures in the genomes of hepatitis C virus (HCV), as well as a new RNA functional …


In Vitro Elucidation Of The Role And Mechanism Of Rankl In Tnf-And Il-1-Mediated Osteoclast Formation And Function, Joel Jules Jan 2010

In Vitro Elucidation Of The Role And Mechanism Of Rankl In Tnf-And Il-1-Mediated Osteoclast Formation And Function, Joel Jules

All ETDs from UAB

The receptor activator of NF-қB (RANK) ligand (RANKL) and its receptor RANK play a critical role in osteoclast biology. RANK has three tumor necrosis factor receptor associated factor (TRAF)-binding motifs [PFQEP369-373 (Motif 1), PVQEET559-564 (Motif 2), and PVQEQG604-609 (Motif 3)] that regulate osteoclast formation and function. RANK also contains a TRAF-independent motif (IVVY535-538) that commits bone marrow macrophages (BMMs), which are osteoclast precursors, to the osteoclast lineage for osteoclastogenesis. Notably, tumor necrosis factor-α (TNF) and interlukin-1 (IL-1) utilize TRAFs to initiate most of the signaling pathways known to be activated by RANKL but fail to form osteoclasts unless attended by …


Structural And Functional Study Of P58(Ipk), Jiahui Tao Jan 2010

Structural And Functional Study Of P58(Ipk), Jiahui Tao

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P58(IPK) is an endoplasmic reticulum (ER)-resident protein which is upregulated during unfolded protein response (UPR). In stressed cells, P58(IPK) functions to restore protein folding equilibrium in ER by suppressing protein aggregation and promoting protein folding. P58(IPK) associates with the unfolded protein via its N-terminal TPR domain and presents it to BiP (binding immunoglobulin protein) for subsequent folding. P58(IPK) belongs to the Hsp40 family. Collectively, P58(IPK) is a stress-inducible ER-resident molecular chaperone. In this dissertation, we report the crystal structure of P58(IPK) TPR domain to 2.5 Å resolution. In the crystal structure, the 43-kDa TPR domain consists of nine tandemly linked …


Heparanase Drives The Aggressive Myeloma Phenotype: Preclinical Development Of A Heparanase Inhibitor For The Treatment Of Multiple Myeloma, Joe Ritchie Jan 2010

Heparanase Drives The Aggressive Myeloma Phenotype: Preclinical Development Of A Heparanase Inhibitor For The Treatment Of Multiple Myeloma, Joe Ritchie

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Heparanase, an endoglycosidase which cleaves heparan sulfate chains at specific sites, is rarely expressed in normal tissues but becomes evident in many human cancers. We have previously shown that heparanase promotes myeloma growth and angiogenesis through modulation of the tumor microenvironment. Recognition that heparanase drives the aggressive myeloma phenotype has led to new strategies designed to therapeutically target this enzyme. SST0001, a non-anticoagulant heparin that is 100% N-acetylated and 25% glycol split, was previously described as a potent inhibitor of heparanase activity in vitro, and, in limited in vivo experiments, SST0001 was identified to have efficacy as an anti-tumor agent …


Roles Of Adiponectin And Its Receptors In Foam Cell Transformation, Ling Tian Jan 2010

Roles Of Adiponectin And Its Receptors In Foam Cell Transformation, Ling Tian

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Macrophages play a critical role in the initiation and progression of atherosclerosis by producing pro-inflammatory mediators and transforming into lipid-laden foam cells. The prevention of lipid accumulation and inflammation in macrophage foam cells, therefore, represents a promising target for effective therapy for atherosclerosis. Adiponectin is a circulating cytokine primarily expressed and secreted by adipocytes, and is downregulated in obesity-linked diseases including type 2 diabetes, coronary artery disease and hypertension. In oxidized low-density lipoprotein (oxLDL)-induced human THP-1 macrophage foam cells, adiponectin suppresses lipid accumulation through decreasing lipid uptake and increasing high-density lipoprotein (HDL)-mediated lipid efflux. The potential mechanisms that adiponectin utilizes …


Usp14: A Link Between The Proteasome And Synaptic Function, Brandon John Walters Jan 2010

Usp14: A Link Between The Proteasome And Synaptic Function, Brandon John Walters

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The ubiquitin proteasome system (UPS) is a coordinated process by which the cell can control protein distribution and abundance. Proteins are marked for turnover by the construction of a polyubiquitin chain on the protein substrate. Once engaged by the proteasome, the ubiquitin side-chain is disassembled by proteasomal deubiquitinating enzymes (DUBs), preventing entry of ubiquitin into the proteasome and recycling it for use in future reactions. One of the DUBs that resides on the proteasome is Ubiquitin Specific Protease 14 (Usp14), which is mutated in the ataxia (axJ) mice. This mutation results in pronounced physical deficits and, unexpectedly, a deficit in …