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Articles 1 - 30 of 72
Full-Text Articles in Medicine and Health Sciences
Role Of The Cystine/Glutamate Exchanger In Glioma Cell Biology, Toyin Adeyemi Ogunrinu
Role Of The Cystine/Glutamate Exchanger In Glioma Cell Biology, Toyin Adeyemi Ogunrinu
All ETDs from UAB
Changes in the glioma microenvironment including oxygen (O2) levels, supply of amino acid such as L-glutamate and L-cystine and glutathione (GSH) concentrations play a critical role in glioma biology. Previous data from our laboratory and others have implicated the L-cystine/L-glutamate exchanger, system xc- in the invasion and proliferation of cancers including glioma. The central aim of this dissertation was to characterize the contribution of L-cystine uptake, GSH synthesis and L-glutamate release to migration and proliferation of glioma cells. In my first study, I examined the role of system xc- mediated L-glutamate release on glioma migration. I show that activation of …
Mechanisms And Consequences Of Thy-1 Shedding, John Edwin Bradley
Mechanisms And Consequences Of Thy-1 Shedding, John Edwin Bradley
All ETDs from UAB
Idiopathic Pulmonary Fibrosis (IPF) is characterized by chronic fibrosis in the lung interstitium of unknown etiology, and causes death within 2 to 4 years after diagnosis. There are no clinical interventions save for lung transplantation that give any survival benefit. Aberrant collagen deposition and aggregates of proliferating fibroblasts and myofibroblasts called fibroblastic foci (FF) are the classic features of IPF. Therefore, the cell type most often implicated as pathogenic in IPF is the fibroblast, especially its differentiated phenotype, the myofibroblast. Fibroblasts are a remarkably heterogeneous cell type. Expression of the cell surface glycoprotein Thy-1 (Thymocyte differentiation antigen 1) delineates a …
Mitochondrial Genetics And Function In Cardiovascular Disease Susceptibility, Jessica L. Brenneman
Mitochondrial Genetics And Function In Cardiovascular Disease Susceptibility, Jessica L. Brenneman
All ETDs from UAB
While progress has been made in understanding the development and progression of cardiovascular disease (CVD), the mechanisms of CVD risk and initiation are not completely understood. It is widely accepted that CVD is the result of a combination of genetic and environmental factors but it is not known why some populations with otherwise similar risk factors appear more susceptible to CVD than others. It is also known that different strains of laboratory mice have distinct susceptibilities to CVD development. For example, C3H mice are resistant to diet induced atherogenesis whereas C57 animals are susceptible. We have also found that the …
Erythropoiesis In The Absence Of Adult Hemoglobin, Shanrun Liu
Erythropoiesis In The Absence Of Adult Hemoglobin, Shanrun Liu
All ETDs from UAB
The mammalian erythrocyte is a highly specialized blood cell that differentiates via an orderly series of committed progenitors in the bone marrow in a process termed erythropoiesis. During erythroid development, hemoglobin synthesis increases from early erythroid progenitors to mature enucleated red blood cells (RBCs). Although hemoglobin is the most extensively studied protein in history, the role, if any, that hemoglobin plays in erythroid development remains obscure. In this study, I ask the question what happens during erythropoiesis in the absence of hemoglobin. I demonstrate that my original hypothesis that excess free heme would accumulate in the absence of globin chain …
Role Of Calcium-Activated Potassium Channels In Glioblastoma Volume Regulation, Michael Bryan Mcferrin
Role Of Calcium-Activated Potassium Channels In Glioblastoma Volume Regulation, Michael Bryan Mcferrin
All ETDs from UAB
The most common and most malignant gliomas are the Grade IV Glioblastoma Multiforme (GBM), characterized by a highly proliferative tumor mass and extremely invasive phenotype that allows for profuse dispersal of tumor cells throughout the brain. GBM cells must specifically regulate their cell volume to thrive within the edematous tumor mass and infiltrate throughout the tortuous extracellular spaces of the brain. These rapid and directed volume changes are governed by the controlled flux of potassium and chloride ions across the cell membrane, which move osmotically obliged water. The goal of this dissertation was to investigate the role of calcium-activated potassium …
The Sodium-Potassium-Chloride Cotransporter In Glioma Biology, Brian R. Haas
The Sodium-Potassium-Chloride Cotransporter In Glioma Biology, Brian R. Haas
All ETDs from UAB
The most common malignant primary brain tumor, gliomas usually derive from glial cells including oligodendrocytes and astrocytes. These tumors are characterized by high rates of proliferation and aberrant migration which make them notoriously difficult to treat using standard treatment paradigms such as chemotherapy and radiation. In order for glioma cells to migrate into the surrounding brain tissue, they must undergo rapid and dynamic volume changes. Previous work published by the Sontheimer laboratory and others indicates glioma utilize the flux of ions across the cell membrane to aid in volume changes associate with cell migration. In this dissertation, I show the …
Determining The Functional Role Of Trem-Like Transcript 2 In The Innate Immune Response, Matthew Martin Halpert
Determining The Functional Role Of Trem-Like Transcript 2 In The Innate Immune Response, Matthew Martin Halpert
All ETDs from UAB
TLT2 is one of four receptors conserved between mouse and human within the TREM locus, and is expressed on B cells, macrophages, and neutrophils. TLT2 ligation on murine macrophages induces the production of chemokines and growth factors, as evidenced by ex vivo treatment with anti-TLT2 mAbs. This treatment did not lead to the upregulation of activation markers such as CD69 or costimulatory molecules such as CD80 and CD86, indicating a specific response following TLT2 ligation. This is recapitulated in vivo following injection of anti-TLT2 mAbs resulting in the production of chemokines and growth factors, which ultimately lead to enhanced neutrophil …
Bone Morphogenetic Protein Signaling Pathways During Mouse Heart Development: Roles For Chd7 And Mycn, Cristina Harmelink
Bone Morphogenetic Protein Signaling Pathways During Mouse Heart Development: Roles For Chd7 And Mycn, Cristina Harmelink
All ETDs from UAB
Bone Morphogenetic Protein (BMP) signaling pathways are imperative for proper heart development. BMP ligands bind serine threonine kinase receptors, which activate intracellular receptor-regulated SMAD proteins. SMAD1, SMAD5, and SMAD8 transduce BMP signals from the cytoplasm to the nucleus, where they regulate transcription. We have investigated two aspects of BMP signaling during mouse cardiogenesis: identifying SMAD1-interacting proteins and exploring the roles of a known BMP target, Mycn, in the developing myocardium. Chromodomain helicase DNA binding protein 7 (CHD7) is a highly conserved transcription factor that promotes protein synthesis, proliferation, and differentiation. Haploinsufficiency for CHD7 causes CHARGE syndrome, a developmental disorder characterized …
Analysis Of The Structural And Kinetic Properties Of Sult2a1 Induced By The Binding Of 3'-Phosphoadenosine-5'-Phosphosulfate, Ian Thomas Cook
Analysis Of The Structural And Kinetic Properties Of Sult2a1 Induced By The Binding Of 3'-Phosphoadenosine-5'-Phosphosulfate, Ian Thomas Cook
All ETDs from UAB
Sulfation is an important Phase II drug metabolism reaction catalyzed by the cytosolic sulfotransferases (SULTs). SULT2A1 is a major SULT in liver and adrenal cortex that has been reported to sulfate a wide variety of substrates including bile acids, steroids, and drugs. The crystal structures of SULT2A1 suggest that PAPS binding causes a structural change. This study examines the kinetic changes in SULT2A1 caused by PAPS binding using computer modeling, enzyme kinetics, binding studies, and mammalian cells expressing SULT2A1. The data presented clearly demonstrate that the binding of PAPS changes the affinity of some substrates to SULT2A1 resulting in different …
Understanding Molecular Mechanisms Of Breast Cancer Metastasis Using Genetically-Engineered Mice, Leah M. Cook
Understanding Molecular Mechanisms Of Breast Cancer Metastasis Using Genetically-Engineered Mice, Leah M. Cook
All ETDs from UAB
Morbidity and mortality of breast cancer patients are drastically increased when primary tumor cells metastasize to distant organ sites. Effective treatment of metastatic disease has been limited; therefore, an increased molecular understanding to identify biomarkers and therapeutic targets is needed. Breast cancer metastasis suppressor 1 (BRMS1) suppresses development of metastases when expressed in a variety of cancer types, including metastatic mammary carcinoma. Little is known of Brms1 function throughout the initiation and progression of mammary carcinoma. Thus Brms1 transgenic mice (derived on C57BL/6 background) were generated by utilizing MMTV promoter expression (for mammary-selective overexpression) or the beta-actin promoter (for ubiquitous …
Structural And Mechanistic Studies On Er Upr Sensor Perk And Mitochondrial Translocon Element Tim44, Wenjun Cui
Structural And Mechanistic Studies On Er Upr Sensor Perk And Mitochondrial Translocon Element Tim44, Wenjun Cui
All ETDs from UAB
The unfolded protein response is one mechanism utilized by endoplasmic reticulum (ER) to maintain the homeostasis between ER protein folding machinery and ER proteins. UPR is induced by three ER transmembrane sensors: IRE1, ATF6 and PERK. PKR-like ER kinase (PERK) can sense the ER stress signal through its luminal domain to activate its cytoplasmic kinase domain catalytic activity. PERK kinase domain belongs to the eIF2α family. Members in this family are activated after being autophosphorylated at their activation loops and then specifically phosphorylate eIF2α at its Ser51 position. Phosphorylation of eIF2α can shutdown the cytosol protein translation from the initiation …
Limited Transplantation Of Antigen-Expressing Hematopoietic Stem Cells Induces Long-Lasting Cytotoxic T Cell Responses And Effect Of Altered Suppressive Myeloid Population On Hiv-Disease Progression, Warren L. Denning
All ETDs from UAB
While each type of cancer and chronic viral infection has its own specific pathology, they share two common mechanisms of immune evasion. The first mechanism is the exhaustion or deletion of antigen-specific T cells. The second mechanism is the formation of an immunosuppressive environment responsible for the block of T cell function. Elicitation of antigen-specific T cells be accomplished by immunotherapy in place of conventional treatments such as HAART and chemotherapy. In addition, immunotherapy can alleviate the side-effects associated with long-term use of conventional therapies while reducing the total cost. The results presented here provide an alternative to conventional methods …
Role Of The Cardiomyocyte Circadian Clock In Modulating Myocardial Physiology And Pathophysiology, David Joseph Durgan
Role Of The Cardiomyocyte Circadian Clock In Modulating Myocardial Physiology And Pathophysiology, David Joseph Durgan
All ETDs from UAB
It is well established that multiple parameters of cardiovascular physiology and pathophysiology exhibit diurnal variations. For example, human heart rate and blood pressure peak during the morning and trough in the evening. Similarly, there is a morning prevalence for the onset of multiple adverse cardiovascular events, including myocardial ischemia, arrhythmias, and sudden cardiac death. Traditionally these rhythms have been attributed to rhythms in neurohumoral stimulation. However recent identification of the circadian clock mechanism in cardiovascular relevant cell types, including the cardiomyocyte, has prompted investigation into its role in modulating myocardial physiology and pathophysiology over the course of the day. Preliminary …
Biological Characterization Of Transmitted Human Immunodeficiency Virus Type-1, Tara Grant Edmonds
Biological Characterization Of Transmitted Human Immunodeficiency Virus Type-1, Tara Grant Edmonds
All ETDs from UAB
Heterosexual transmission of human immunodeficiency virus type&ndash1 (HIV&ndash1) accounts for the majority of infections worldwide, with women representing the larger percentage of infected individuals. The events leading to the transmission of HIV&ndash1 at mucosal surfaces are not well defined. Based on the observations that transmitted viruses nearly exclusively utilize the CCR5 coreceptor, and that in 80% of heterosexual transmissions a single virus variant establishes infection, there appears to be a selection mechanism that allows only a subset of viruses to be transmitted. This genetic bottleneck suggests that transmitted viruses may possess specific phenotypic and/or genotypic properties that allow for their …
Molecular Mechanisms Regulating Caenorhabditis Elegans Sperm Migration, Johnathan Wesley Edmonds
Molecular Mechanisms Regulating Caenorhabditis Elegans Sperm Migration, Johnathan Wesley Edmonds
All ETDs from UAB
Fertilization is the process by which male and female gametes join to give rise to a new organism. Union of sperm and ova requires that sperm be able to successfully locate and migrate towards oocytes in the female reproductive tract. By analyzing the in vitro migration of sperm from diverse species and mapping the complex architecture of their female reproductive tracts, we can infer that sperm must respond to directional cues to seek out the mature oocyte. However, the internal fertilization schemes of most complex animals complicate the analysis of in vivo sperm migration. The transparent epidermis of the nematode …
Broad And Potent Neutralizing Antibody Responses Elicited In Natural Hiv-2 Infection, Rui Kong
Broad And Potent Neutralizing Antibody Responses Elicited In Natural Hiv-2 Infection, Rui Kong
All ETDs from UAB
Little is known about the potency, breadth and epitope specificities of neutralizing antibody (Nab) responses elicited in natural HIV-2 infection. Analysis of plasma specimens from 64 HIV-2 chronically-infected subjects in a single round infectivity assay (JC53bl-13/TZM-bl) revealed median reciprocal IC50 Nab titers of 1.7x105, 2.8x104 and 3.3x104 against three primary virus strains, HIV-27312A, HIV-2ST and HIV-2UC1, respectively. A subset of 5 plasma samples was tested on 17 additional HIV-2 strains, and similarly high Nab titers were observed against all but four viruses. These Nab titers were higher, by orders of magnitude, than HIV-1 Nab titers in plasma from chronically infected …
Sox2/Parylated Parp1 Complexes Regulate Pluripotency, Yi-Shin Lai
Sox2/Parylated Parp1 Complexes Regulate Pluripotency, Yi-Shin Lai
All ETDs from UAB
Embryonic stem cells (ESCs) were first derived from the inner cell mass (ICM) of blastocyst-stage embryos. ESCs are distinguished from other cell types by their pluripotency and unlimited self-replication. ESCs are able to differentiate into multiple cell types that represent all three primary germ layers (ectoderm, mesoderm and endoderm) and can form an entire adult organism. Under defined conditions, ESCs are self-renewable and have an extended life-span without compromising pluripotency. The plasticity of ESCs provides opportunities for regenerative medicine. The recent production of induced pluripotent stem cells (iPSC) offers an ideal "personalized" substitute for ESCs. Overexpression of four transcription factors, …
Elucidation Of The Elongated Fibrillar Structure Of Streptococcus Mutans Antigen I/Ii, Matt Rodney Larson
Elucidation Of The Elongated Fibrillar Structure Of Streptococcus Mutans Antigen I/Ii, Matt Rodney Larson
All ETDs from UAB
Streptococcus mutans (S. mutans) is the causative agent behind dental caries, an infectious disease also known as tooth decay or dental cavities. S. mutans has a cell wall-attached protein known as Antigen I/II (AgI/II) utilized for bacterial adhesion to the tooth surface. Here we have solved the structures of both amino- and carboxy-terminal regions of the AgI/II molecule using X-ray crystallography. Using this structural information we have now built a tertiary model for AgI/II as a fibrillar protein. Further, we have functionally characterized AgI/II and determined minimal regions of AgI/II that are implicated in its adherence to the salivary agglutinin …
Structural And Functional Studies On Group A Streptococcal Bacteriophage Hyaluronidase, Joo Hyoung Lee
Structural And Functional Studies On Group A Streptococcal Bacteriophage Hyaluronidase, Joo Hyoung Lee
All ETDs from UAB
Aberrant hyaluronan production is frequently associated with tumors where the elevated levels of tumoral hyaluronan are often associated with higher expression levels of cellular hyaluronidases that produce saturated hyaluronan fragments with divergent pro-tumoral activities. In this thesis, we provide evidence that different hyaluronan metabolism of bacteriophage hyaluronidase (HylP) elicits distinct alteration in breast cancer cell behavior. We demonstrate through comparative analysis with bovine testicular hyaluronidase (BTH) that higher enzyme activity, specificity for hyaluronan and production of unsaturated oligosaccharides render HylP to have profound effects on growth, migration and invasion activities of breast carcinoma cells, whereas BTH and its saturated metabolites …
In Vivo Interactions Between Virus Genomes And Host Proteins For Members Of The Order Picornavirales, Erik Michael Lenarcic
In Vivo Interactions Between Virus Genomes And Host Proteins For Members Of The Order Picornavirales, Erik Michael Lenarcic
All ETDs from UAB
A significant number of pathogens of economical and medical importance are positive sense RNA viruses. Their genomes enter host cells and subvert them to support virus growth. These large-scale changes involve the co-opting of cellular proteins through interactions with viral RNA and proteins. Characterizing these interactions leads to a better understanding of viral life cycles and the identification of new antiviral therapies. The order Picornavirales contains viruses that infect a wide array of eukaryotes. Their genomes serve as a messenger RNA (mRNA) that is translated by host ribosomes cap-independently through an internal ribosome entry site (IRES). Most members of the …
Qualitative Analysis Of Hiv-1-Specific Cd8 T Cell Responses, Olusimidele Tolulope Akinsiku
Qualitative Analysis Of Hiv-1-Specific Cd8 T Cell Responses, Olusimidele Tolulope Akinsiku
All ETDs from UAB
In the absence of antiretroviral therapy (ART), the majority of individuals infected with human immunodeficiency virus-1 (HIV-1) will develop AIDS. HIV-1-infected controllers are exceptions to the rule; without the use of ART, these individuals spontaneously control virus replication. A better understanding of the immune mechanisms that mediate delayed disease progression, as seen in controllers, will provide valuable insight to the design and development of an effective HIV-1 vaccine. CD8 T cells are important mediators of the antiviral immune response. However, it is unclear which components of the response are critical for long-lasting protection during HIV-1 infection. We first review methods …
Significance And Regulation Of Cd68 Expression In The Osteoclast, Jason Waid Ashley
Significance And Regulation Of Cd68 Expression In The Osteoclast, Jason Waid Ashley
All ETDs from UAB
The mucin-like Lysosome Associated Membrane Protein (LAMP) family member CD68 is a primarily myeloid lineage restricted transmembrane protein that is expressed in macrophages and osteoclasts. While the existence and expression pattern of human CD68 and mouse CD68 (sometimes called macrosialin) are well-known, and these molecules are routinely used as histological markers of tissue macrophages, the functional signific-ance of CD68 expression remains an unanswered question. Our overall goal is to deter-mine the significance and characterize the function of CD68 in osteoclasts and explore the effects of Receptor Activator of Nuclear Factor κB (RANK) signaling on CD68 post-translational modification. To achieve this …
The Effect Of Sulfasalazine On Functional Recovery And Neuropathic Pain Following Spinal Cord Injury, Kelly Dunham Atkins
The Effect Of Sulfasalazine On Functional Recovery And Neuropathic Pain Following Spinal Cord Injury, Kelly Dunham Atkins
All ETDs from UAB
Spinal cord injury (SCI) is a devastating condition resulting in loss of motor function as well as sensory abnormalities. Insight into the pathophysiology of SCI progression has been gained through use of pre-clinical animal models, however these have not been successful in yielding pharmacological interventions for clinical management of SCI. One proposed reason for this discrepancy may be the use of SCI models which are not fully clinically relevant and do not assess the contribution of gray matter pathology to SCI functional outcomes. Post-SCI inflammation is well-documented and may lead to downstream loss of motor function. Additionally, inflammation is thought …
A Recombinant Myeloid-Binding Adenovirus For Targeted Pulmonary Gene Therapy, Michael O. Alberti
A Recombinant Myeloid-Binding Adenovirus For Targeted Pulmonary Gene Therapy, Michael O. Alberti
All ETDs from UAB
Inflammation and airway destruction are hallmarks of many debilitating lung diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), acute lung injury (ALI), and cancer. Gene-based therapeutic interventions that modulate this pathologic inflammatory response are likely to reduce the progressive destruction to lung airways. In this regard, a number of strategies have been evaluated for targeting the pul-monary vasculature; particularly those based on serotype 5 Adenovirus (Ad5). The ad-vantages of Ad over other vector systems include: in vivo stability, low oncogenic poten-tial, and large packaging capacity. Yet, specific and efficient gene delivery to the lung has been hampered …
The Role Of The Classical Nf-Kb Pathway In Hsc Self-Renewal And Acute Myeloid Leukemia, Robert Jason Flynn
The Role Of The Classical Nf-Kb Pathway In Hsc Self-Renewal And Acute Myeloid Leukemia, Robert Jason Flynn
All ETDs from UAB
Acute myeloid leukemia (AML) comprises approximately 25% of newly diagnosed cases of leukemia each year. The constitutive activation of the classical NF-κB signaling pathway has been observed in up to 70% of AML cases, and could be due to mutations upstream involving the PI3K-Akt cascade, which is also constitutively active in a majority of cases. In mice, constitutive activation of Akt either through deletion of the negative regulator of PI3K-Akt, PTEN, or by expression of Myr-Akt induces rapid stem cell loss along with a lethal, transplantable myeloproliferative disorder and AML. These studies show that constitutive Akt and NF-κB signaling distinguish …
The Role Of Ll-37 In Prostate Cancer And Its Potential As A Therapeutic Target, Jonathan Adam Hensel
The Role Of Ll-37 In Prostate Cancer And Its Potential As A Therapeutic Target, Jonathan Adam Hensel
All ETDs from UAB
LL-37 is the only cathelicidin-derived anti-microbial peptide in humans and has been shown to stimulate proliferation, angiogenesis, cellular migration and inhibit apoptosis, in addition to serving as a chemoattractant for leukocytes. It is produced primarily by epithelial cells and leukocytes, and has recently been discovered to be over-expressed in breast, ovarian and lung cancers. Based on these findings, we compared levels of LL-37 expression in benign and cancerous human prostate tissues. Results of this investigation demonstrated that LL-37 is increasingly over-expressed in primary prostate tumors in a grade dependent manner and in metastatic lesions. Since the physiological mechanisms of LL-37 …
Low And High Let Irradiation Of Human Aortic Endothelial Cells Induces Dose And Time Dependent Adhesion Of Monocytes Which Is Mediated By Chemokines Expressed By The Irradiated Endothelium., Saman Fatima Khaled
Low And High Let Irradiation Of Human Aortic Endothelial Cells Induces Dose And Time Dependent Adhesion Of Monocytes Which Is Mediated By Chemokines Expressed By The Irradiated Endothelium., Saman Fatima Khaled
All ETDs from UAB
Exposure to radiation from a variety of sources is associated with increased risk of heart disease and stroke. Since radiation also induces inflammation, a possible mechanism is a change in the adhesiveness of vascular endothelial cells, triggering pro-atherogenic accumulation of leukocytes. To investigate this mechanism at the cellular level, the effect of xrays, iron (Fe56) ions, and protons on adhesiveness of cultured human aortic endothelial cells (HAECs) was determined. HAECs were grown as monolayers and exposed to 0 to 30 Gy X-rays, 0, 2, and 5 Gy Fe56 ions, and 0, 0.5, and 2 Gy protons followed by measurement of …
Ecology And Transmission Of Eastern Equine Encephalitis Virus In The Southeastern United States, Gregory Scott White
Ecology And Transmission Of Eastern Equine Encephalitis Virus In The Southeastern United States, Gregory Scott White
All ETDs from UAB
The virus Eastern Equine Encephalitis virus (EEEV) is a highly pathogenic arthropod-borne virus (arbovirus) present in the US. The virus is listed as a reportable illness to the Centers of Disease Control and Prevention (CDC) and is also listed as a select agent by Human Health and Services (HHS). Studies on EEEV starting back in the 1930's have determined many important facets of the ecology, transmission and evolution of the virus. It is understood that in many endemic foci, the mosquito Culiseta melanura is the primary enzootic vector of the virus. EEEV is thus maintained in an enzootic cycle between …
Functional Interplay Between Trans Factors And Cis-Elements That Govern Il17a&F Transcription, Sarah Kern Whitley
Functional Interplay Between Trans Factors And Cis-Elements That Govern Il17a&F Transcription, Sarah Kern Whitley
All ETDs from UAB
Protective immunity against a variety of infections depends on the amplification and differentiation of naïve antigen-specific CD4 T cells. T helper 17 (Th17) cells are important for defending mucosal barriers from invading extracellular bacterial pathogens. This effector CD4 lineage is characterized by production of the cytokines IL-17A, IL-17F, IL-21, and IL-22, which elicit influx of inflammatory cells to promote pathogen clearance. The cytokines IL-6 and TGF&beta are the principal factors that initiate Th17 lineage development, and the STAT3-inducing cytokines IL-21 and IL-23 assist and/or maintain the Th17 developmental program. Recently, an additional cytokine has been demonstrated to encourage Th17 differentiation: …
High Resolution Analysis Of Clonal Pluripotent Stem Cell Lentiviral Gene Therapy In A Mouse Model Of Beta-Thalassemia, Rui Yang
All ETDs from UAB
Gene therapy for hematopoietic disorders using viral vectors has achieved significant clinical benefit. However this approach has been held back by adverse genotoxic events due to random viral integration into the genome. A better understanding of viral transgene chromosomal position effects is critical for the design of safer viral vectors and clinical protocols. However, detailed analysis of viral transgenes is hampered by the heterogeneity of the viral-transduced bone marrow cell populations. I hypothesized that viral transduction of pluripotent stem cells would enable the clonal analysis of viral transgene expression, safety, and efficacy both in vitro and in vivo. Here I …