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Full-Text Articles in Medicine and Health Sciences

A Recombinant Myeloid-Binding Adenovirus For Targeted Pulmonary Gene Therapy, Michael O. Alberti Jan 2011

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 …

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The Effect Of Sulfasalazine On Functional Recovery And Neuropathic Pain Following Spinal Cord Injury, Kelly Dunham Atkins Jan 2011

The Effect Of Sulfasalazine On Functional Recovery And Neuropathic Pain Following Spinal Cord Injury, Kelly Dunham Atkins

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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 …

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Significance And Regulation Of Cd68 Expression In The Osteoclast, Jason Waid Ashley Jan 2011

Significance And Regulation Of Cd68 Expression In The Osteoclast, Jason Waid Ashley

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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 …

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Role Of The Cardiomyocyte Circadian Clock In Modulating Myocardial Physiology And Pathophysiology, David Joseph Durgan Jan 2011

Role Of The Cardiomyocyte Circadian Clock In Modulating Myocardial Physiology And Pathophysiology, David Joseph Durgan

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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 …

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The Role Of The Classical Nf-Kb Pathway In Hsc Self-Renewal And Acute Myeloid Leukemia, Robert Jason Flynn Jan 2011

The Role Of The Classical Nf-Kb Pathway In Hsc Self-Renewal And Acute Myeloid Leukemia, Robert Jason Flynn

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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 …

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The Study Of Intracellular Signaling Pathways In Schizophrenia, Adam Funk Jan 2011

The Study Of Intracellular Signaling Pathways In Schizophrenia, Adam Funk

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INTRACELLULAR SIGNALING AND INTEGRATION ABNORMALITIES IN SCHIZOPHRENIA Adam J. Funk DEPARTMENT OF NEUROBIOLOGY ABSTRACT The pathophysiology of schizophrenia is complex and diverse, with many classes of receptors, neurotransmitters, and brain regions implicated in this illness. The many hypotheses proposed have yet to fully explain the heterogeneity of the genetic, postmor-tem, and clinical evidence. It is the goal of this dissertation to integrate the current hy-potheses of schizophrenia into a unified hypothesis of abnormal intracellular signaling and signal integration. Inconsistencies in genetic and postmortem findings suggest that the development of schizophrenia is multifaceted, and the heterogeneity of symptoms supports the hypothesis …

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Intracellular Distribution Of Glycogen Synthase Kinase-3beta In The Brain, Johanna C. Gandy Jan 2011

Intracellular Distribution Of Glycogen Synthase Kinase-3beta In The Brain, Johanna C. Gandy

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The widely distributed serine/threonine kinase glycogen synthase kinase 3beta is well known for its multiple functions in the health brain tissue, which include cell fate, neuronal growth and remodeling, synaptic plasticity, and neuroinflammation. However much of GSK3beta focuses on its abnormal functions in neurological disorders like Alzheimer's Disease and psychiatric disorders. To maintain normal GSK3beta function in the brain, this constitutively active kinase must be strictly regulated. Many factors within the cell work together to influence GSK3beta activity. Two ways to regulate GSK3beta activity are through phosphorylation by upstream kinases or the formation of protein complexes that block substrate binding. …

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Human Cytomegalovirus Ul97 Kinase Activity Modifies Cell Cycle Checkpoint Regulators, Rachel Brooke Gill Jan 2011

Human Cytomegalovirus Ul97 Kinase Activity Modifies Cell Cycle Checkpoint Regulators, Rachel Brooke Gill

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Human cytomegalovirus (CMV) infection results in destructive infections in neonates and immunocompromised individuals. Being the primary congenital infection in the United States, it can often result in permanent neurological deficits in infants. The current therapies for CMV infections all target the viral DNA polymerase and also have dose-limiting toxicities. Isolates resistant to ganciclovir (GCV), the therapy of choice, can sometimes overwhelm immunocompromised hosts. Better therapies for this infection are required. The CMV UL97 kinase is a key enzyme in the treatment of CMV infection because it phosphorylates GCV. Additionally, maribavir (MBV) specifically inhibits UL97 kinase activity and inhibits viral replication. …

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Oxidative Stress And Xanthine Oxidase In Acute And Chronic Cardiac Volume Overload In Rats, James Douglas Gladden Jan 2011

Oxidative Stress And Xanthine Oxidase In Acute And Chronic Cardiac Volume Overload In Rats, James Douglas Gladden

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Mechanisms of left ventricular dysfunction in cardiac volume overload (VO) are not well understood and there is no medical therapy. Cardiac VO is marked by eccentric remodeling and contractile dysfunction ultimately resulting in cardiac failure. Oxidative stress is implicated in the pathophysiology of heart failure and recent evidence suggests xanthine oxidase (XO) plays a role in VO. To study VO, we used a rat model of aortocaval fistula (ACF). ACF results in early diastolic stress on the left ventricle (LV) and recapitulates the progressive nature of heart failure with contractile function being initially maintained and then depressed by 6 weeks. …

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Mitochondrial Genetics And Function In Cardiovascular Disease Susceptibility, Jessica L. Fetterman Jan 2011

Mitochondrial Genetics And Function In Cardiovascular Disease Susceptibility, Jessica L. Fetterman

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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 …

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Identification And Characterization Of Novel Adenosine Cleavage Enzymes In Mycobacteria, Kajal Buckoreelall Jan 2011

Identification And Characterization Of Novel Adenosine Cleavage Enzymes In Mycobacteria, Kajal Buckoreelall

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Tuberculosis (TB) is one of the leading infectious diseases in the world. An estimated one third of the world's population is infected with Mycobacterium tuberculosis, the causative pathogen of TB. With the emergence of drug resistant strains of the mycobacterium, and the HIV-TB coinfection epidemic, TB remains a global health emergency. Purine metabolism is an essential cellular component to all living cells. Previous studies have shown that differences exist between mycobacterial and human purine metabolism. One of the differences was in the metabolism of adenosine (Ado), whose cleavage was observed in mycobacterial cells whereas Ado cleavage is inefficient in human …

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Pathophysiology Of Dyt1 Dystonia: Targeted Mouse Models, Chad Christopher Cheetham Jan 2011

Pathophysiology Of Dyt1 Dystonia: Targeted Mouse Models, Chad Christopher Cheetham

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DYT1 dystonia is an inherited movement disorder caused by a trinucleotide deletion (DeltaGAG) in the DYT1 (TOR1A) gene, which codes for the torsinA protein. Dr. Yuqing Li's laboratory previously reported the characterization of a DYT1 dystonia mouse model, a knock-in carrying DeltaGAG in Dyt1 (KI), which displays a motor learning deficit of motor skill transfer. We report here that this motor learning deficit was reversed with an anticholinergic drug, trihexyphenidyl (THP), a drug commonly used to treat movement problems in dystonia patients. We further show a potential substrate for the pathophysiology, a reduction in D2 receptors in the striatum in …

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Analysis Of The Structural And Kinetic Properties Of Sult2a1 Induced By The Binding Of 3'-Phosphoadenosine-5'-Phosphosulfate, Ian Thomas Cook Jan 2011

Analysis Of The Structural And Kinetic Properties Of Sult2a1 Induced By The Binding Of 3'-Phosphoadenosine-5'-Phosphosulfate, Ian Thomas Cook

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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 …

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Differential Contributions Of C-Kit Activating Mutations To Promotion Of Aml1-Eto Associated Neoplasia, Heidi Jean Nick Jan 2011

Differential Contributions Of C-Kit Activating Mutations To Promotion Of Aml1-Eto Associated Neoplasia, Heidi Jean Nick

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The t(8;21) translocation, which generates an AML1-ETO fusion protein (also known as RUNX1-ETO), is one of the most frequent cytogenetic abnormalities in acute myeloid leukemia (AML). Murine studies have demonstrated that AML1-ETO promotes the accumulation of myeloid progenitor cells with self-renewal capability and impaired differentiation capacity. However, AML1-ETO+ mice do not progress to AML in the absence of additional mutations, suggesting that expression of the translocation is insufficient for leukemogenesis. This hypothesis is supported by studies demonstrating the persistence of AML1-ETO-expressing hematopoietic progenitors obtained from patients in long-term clinical remission. Mutations affecting receptor tyrosine kinases, particularly c-KIT, are commonly detected …

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Pediatric Obesity And Traumatic Lower Extremity Long Bone Fracture Outcomes, Ian Charles Backstrom Jan 2011

Pediatric Obesity And Traumatic Lower Extremity Long Bone Fracture Outcomes, Ian Charles Backstrom

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Background: Pediatric obesity is associated with lower extremity injuries and poor outcomes after blunt trauma. Our aim was to determine if obese pediatric patients with femur and tibia fractures have more severe injury patterns and worse outcomes compared to non-obese patients. Methods: We performed a retrospective cohort study of obese and non-obese pediatric patients with femur or tibia fractures treated at two Level-1 trauma centers from 2004-2010. Patients weighing ≥ 95th percentile for age and gender were classified as obese. Patients were compared regarding demographics, Injury Severity Score (ISS), intra-abdominal, and orthopedic injuries. Outcomes included fracture treatment, orthopedic complications, ICU …

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Sensitization Of Glioma To Death Receptor 5-Mediated Apoptosis Through Genotoxic Stress And Cell Cycle Disruption: A Study Of Mechanism, Michael L. Belenky Jan 2011

Sensitization Of Glioma To Death Receptor 5-Mediated Apoptosis Through Genotoxic Stress And Cell Cycle Disruption: A Study Of Mechanism, Michael L. Belenky

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Our laboratory reported that a combination of ionizing radiation (IR) or temozolomide (Tmz), a DNA methylating agent clinically approved against glioblastoma multiforme (GBM), a type of human brain cancer, and TRA-8, an anti-DR5 monoclonal antibody produced synergistic cytotoxicity in GBM cells in culture and in mouse xenograft models through an yet unknown mechanism. I hypothesized that understanding of the synergy phenomenon can offer an insight into the nature of GBM vulnerability. The goals of this investigation were two-fold - to elucidate the mechanism of this enhancement in cytotoxicity, and to improve understanding of DR5 mediated apoptosis toward improvement of current …

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Exopolysaccharide: A Multi-Faceted Role In Mycoplasma Pulmonis, Jeffrey R. Bolland Jan 2011

Exopolysaccharide: A Multi-Faceted Role In Mycoplasma Pulmonis, Jeffrey R. Bolland

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The recently characterized exopolysaccharide of Mycoplasma pulmonis, EPS-I, has been identified as modulating the susceptibility to complement-mediated lysis and binding to host mucosal epithelium. M. pulmonis produces family of size- and phase-variable lipoproteins called Vsa. Previous evidence has strongly demonstrated that the length of the tandem repeat region of the M. pulmonis Vsa protein is associated with the susceptibility to the host innate immune system through complement-mediated lysis. Mycoplasmas producing a long form of Vsa, containing about 40 repeats, are resistant complement whereas strains that produce the short form of Vsa, 5 repeats or fewer, are susceptible. Furthermore, the size …

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Expanding Genetic Analysis Of Patients With A Neurofibromatosis Type 1-Like Phenotype, Emily Spencer Jan 2011

Expanding Genetic Analysis Of Patients With A Neurofibromatosis Type 1-Like Phenotype, Emily Spencer

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Neurofibromatosis Type 1, a common autosomal dominant disorder with neuro-cardio- facio-cutaneous presentation, is caused by mutations in the NF1 gene, a negative regulator of RAS-MAPK signaling. The presentation of NF1 is overlapping, yet clinically distinct from other diseases of RAS-MAPK signaling. An RNA-based comprehensive approach for mutation detection identifies an NF1 alteration in over 95% of non-founder NF1 patients with a classical NF1 presentation. However, no NF1 mutation was identified in 54.2% of the 2432 patients referred for molecular diagnostics due to the presence one or more NF1 related sign between August 2003 and July 2007. In order to clarify …

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The Role Of Protein Folding And Protein Trafficking In Human Disease, Cristy Davette Tower-Gilchrist Jan 2011

The Role Of Protein Folding And Protein Trafficking In Human Disease, Cristy Davette Tower-Gilchrist

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This dissertation documents my findings in two unrelated projects. Project 1: Expansion of CAG repeats encoding glutamine in huntingtin and ataxin 3 causes the neurodegenerative diseases Huntington's disease (HD) and spinocerebellar ataxia 3 (SCA3), respectively. Both poly-glutamine (polyQ) expanded proteins misfold and ag-gregate within the cell. Preventing aggregation of polyQ proteins through molecular or pharmacological approaches provide therapeutic advantage in animal models of HD and SCA3. I hypothesized that the UL97 kinase encoded by the human cytomegalovirus (HCMV) may be able to prevent the aggregation of polyQ proteins. Initially, I showed that the UL97 kinase prevents the deposition of aggregates …

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The Requisite Role Of Dectin-1 And Il-17 In Innate Host Defense Against Aspergillus Fumigatus, Jessica L. Werner Jan 2011

The Requisite Role Of Dectin-1 And Il-17 In Innate Host Defense Against Aspergillus Fumigatus, Jessica L. Werner

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Immune suppression increases the incidence of invasive fungal infections, particularly those caused by the opportunistic mold Aspergillus fumigatus. We show that non-immunosuppressed mice lacking the beta-glucan receptor Dectin-1 (Dectin-1-/-) are more susceptible to intratracheal challenge with A. fumigatus than control mice, exhibiting >80% mortality within 5 days; ultimately attributed to a compromise in respiratory mechanics. In response to A. fumigatus challenge, Dectin-1-/- mice demonstrated impaired inflammatory response as seen through defective cytokine and chemokine production, which resulted in insufficient lung neutrophil recruitment and uncontrolled A. fumigatus lung growth. Alveolar macrophages from Dectin-1-/- mice failed to produce proinflammatory mediators in response …

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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 Jan 2011

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

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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 …

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The Role Of Trib3 In Insulin Resistance: Its Action As Nutrient Sensor And Regulator Of Insulin Action, Jiarong Lamiquiz Jan 2011

The Role Of Trib3 In Insulin Resistance: Its Action As Nutrient Sensor And Regulator Of Insulin Action, Jiarong Lamiquiz

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THE ROLE OF TRIB3 IN INSULIN RESISTANCE: ITS ACTION AS NUTRIENT SENSOR AND REGULATOR OF INSULIN ACTION JIARONG LIU LAMIQUIZ PATHOLOGY ABSTRACT Insulin resistance is a hallmark of Type 2 diabetes (T2DM). A reduced capacity for insulin to stimulate increases in glucose uptake and glucose oxidation in insulin sensitive tissues, such as skeletal muscle and adipose tissue, are common defects in patients with insulin resistance, T2DM, and other related diseases. Tribbles homolog 3 (TRIB3) has been demonstrated to play a role in insulin resistance by serving as a negative regulator of Akt in mouse liver, fat, and pancreas. In a …

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Elucidation Of The Elongated Fibrillar Structure Of Streptococcus Mutans Antigen I/Ii, Matthew Rodney Larson Jan 2011

Elucidation Of The Elongated Fibrillar Structure Of Streptococcus Mutans Antigen I/Ii, Matthew Rodney Larson

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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 …

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Erythropoiesis In The Absence Of Adult Hemoglobin, Shanrun Liu Jan 2011

Erythropoiesis In The Absence Of Adult Hemoglobin, Shanrun Liu

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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 …

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The Effects Of Simvastatin On Learning And Memory Mechanisms In Mice, Robert Mans Jan 2011

The Effects Of Simvastatin On Learning And Memory Mechanisms In Mice, Robert Mans

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Statins, a widely prescribed class of cholesterol-lowering drug, inhibit HMG-CoA reductase, the rate-limiting enzyme in the cholesterol biosynthetic pathway. Due to the identification of cholesterol as a risk factor for developing Alzheimer's disease (AD), a number of studies have examined whether statins are neuroprotective against developing AD or dementia. While some epidemiological studies do indicate a lower prevalence of AD in people taking statins, other reports are contradictory. A consensus has therefore not been reached regarding the neuroprotective effects of statin treatment. Aside from the well-characterized reduction in circulating cholesterol resulting from statin therapy, numerous cholesterol-independent, pleiotropic effects have been …

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Analysis Of Nphp Complex Genetic Interactions Associated With Human Cilia Disorders, Svetlana Viktorovna Masyukova Jan 2011

Analysis Of Nphp Complex Genetic Interactions Associated With Human Cilia Disorders, Svetlana Viktorovna Masyukova

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Primary cilia are antenna-like organelles that extend from the surface of almost all mammalian cell types. They regulate many signaling pathways and sense physical and chemical changes in the extracellular environment. Defects in primary cilia cause several human disorders of different severity collectively called ciliopathies, including nephronophthisis (NPHP), Joubert syndrome (JBTS), and Meckel-Gruber syndrome (MKS). Numerous MKS, JBTS and NPHP genes have been identified but in most cases of these ciliopathies the genetic defect is unknown. Despite the fact that NPHP, JBTS and MKS patients present with distinct clinical features, they have mutations in identical genes. This can be explained …

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Hemoglobin Switching, Thalassemia And Sickle Cell Disease In Humanized Knockin Mice, Sean Mcconnell Jan 2011

Hemoglobin Switching, Thalassemia And Sickle Cell Disease In Humanized Knockin Mice, Sean Mcconnell

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In this dissertation we describe knockin mouse models for the study of human hemoglobin disorders. These knockin human globin genes, in contrast to transgenes, replace the adult mouse globin genes, remain under control of endogenous mouse globin enhancer sequences and are inherited in a manner identical to globin alleles in man. Starting with various knockin alleles composed of unique human alpha, beta and gamma globin gene sequences, we evaluate several allele combinations towards our goal of generating improved models of thalassemia and sickle cells disease. We show that humanized knockin mice complete a fetal to adult hemoglobin switch during postnatal …

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High Resolution Analysis Of Clonal Pluripotent Stem Cell Lentiviral Gene Therapy In A Mouse Model Of Beta-Thalassemia, Rui Yang Jan 2011

High Resolution Analysis Of Clonal Pluripotent Stem Cell Lentiviral Gene Therapy In A Mouse Model Of Beta-Thalassemia, Rui Yang

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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 …

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Piggybac Transposon Mutagenesis In Human And Mouse Stem Cells, Tingting Zhang Jan 2011

Piggybac Transposon Mutagenesis In Human And Mouse Stem Cells, Tingting Zhang

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The most common genetic diseases worldwide, £] thalassemia and Sickle Cell Anemia (SCA) result from mutations in the adult £] globin gene. One promising therapeutic method to ameliorate these diseases is to reactivate the endogenous fetal f× globin gene. I hypothesize that an erythroid mutagenic transposon system can be used to activate f× globin gene expression. To test this hypothesis three lines of genetically modified mice were generated and bred together. The first is a transgenic mouse line that contains a multicopy array of erythroid mutagenic PiggyBac (PB) transposons. The second transgenic mouse line expresses the PB transposase (TPase) from …

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Characterization Of Tbx20 Isoforms And Protein Interactions In Heart Development, Paige Debenedittis Jan 2011

Characterization Of Tbx20 Isoforms And Protein Interactions In Heart Development, Paige Debenedittis

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Proper cardiogenesis is critical for the development of vertebrates. Abnormalities in cardiogenesis can lead to congenital heart defects (CHDs), which occur in approximately 1% of live births. The cardiac transcription factor network contains different transcription factor families which direct the expression of critical cardiac genes. Determining how the cardiac transcription factors are regulated will provide insight in the mechanisms of cardiogenesis and CHDs. The T-box (TBX) transcription factor family is an ancient gene family important for development. Several TBX genes are expressed within the developing heart and play critical roles in differentiation, proliferation, and morphogenesis. One important TBX protein is …

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