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Contribution Of Ectodomain Mutations In Epidermal Growth Factor Receptor To Signaling In Glioblastoma Multiforme, Marta L. Rojas

Dissertations and Theses (Open Access)

CONTRIBUTION OF ECTODOMAIN MUTATIONS IN EPIDERMAL GROWTH FACTOR RECEPTOR TO SIGNALING IN GLIOBLASTOMA MULTIFORME

Publication No._________

Marta Rojas, M.S.

Supervisory Professor: Oliver Bögler, Ph.D.

The Cancer Genome Atlas (TCGA) has conducted a comprehensive analysis of a large tumor cohort and has cataloged genetic alterations involving primary sequence variations and copy number aberrations of genes involved in key signaling pathways in glioblastoma (GBM). This dataset revealed missense ectodomain point mutations in epidermal growth factor receptor (EGFR), but the biological and clinical significance of these mutations is not well defined in the context of gliomas.

In our study, we focused on understanding …

Dual Targeting Of Tumor Angiogenesis And Chemotherapy By Endostatin- Cytosine Deaminase-Uracil Phosphoribosyltransferase, Chun-Te Chen

Dissertations and Theses (Open Access)

Antiangiogenesis is a promising anti-tumor strategy through inhibition tumor vascularformation to suppress tumor growth. Targeting specific VEGF/R has been showntherapeutic benefits in many cancer types and become a first approvedantiangiogenic modalities by Food and Drug Administration (FDA) in United States.However, interruption of homeostasis in normal tissues that is likely due to theinhibition of VEGF/R signaling pathway induces unfavorable side effects. Moreover,cytostatic nature of antiangiogenic drugs frequently causes less tumor cell specifickilling activity, and cancer cells escaped from cell death induced by these drugseven gain more malignant phenotypes, resulting in tumor invasion and metastasis.To overcome these issues, we developed a novel …

Development Of A Bayesian Joint Logistic Model To Better Study The Association Between Haplotypes And Disease, Anthony M. D'Amelio Jr

Dissertations and Theses (Open Access)

In 2011, there will be an estimated 1,596,670 new cancer cases and 571,950 cancer-related deaths in the US. With the ever-increasing applications of cancer genetics in epidemiology, there is great potential to identify genetic risk factors that would help identify individuals with increased genetic susceptibility to cancer, which could be used to develop interventions or targeted therapies that could hopefully reduce cancer risk and mortality.

In this dissertation, I propose to develop a new statistical method to evaluate the role of haplotypes in cancer susceptibility and development. This model will be flexible enough to handle not only haplotypes of any …

Glycogen Synthase Kinase 3 Is Required For Optimal Akt Activation, Debora S. Bruno

Dissertations and Theses (Open Access)

The phosphatidylinositol 3-kinase (PI3K) pathway, through its major effector node AKT, is critical for the promotion of cell growth, division, motility and apoptosis evasion. This signaling axis is therefore commonly targeted in the form of mutations and amplifications in a myriad of malignancies. Glycogen synthase kinase 3 (GSK3) was first discovered as the kinase responsible for phosphorylating and inhibiting the activity of glycogen synthase, ultimately antagonizing the storage of glucose as glycogen. Its activity counteracts the effects of insulin in glucose metabolism and AKT has long been recognized as one of the key molecules capable of phosphorylating GSK3 and inhibiting …

Applications Of Ephb4 Receptor Specific Peptides In Targeted Cancer Imaging And Therapy, Miao Huang

Dissertations and Theses (Open Access)

EphB4 receptors, a member of the largest family of receptor tyrosine kinases, are found over-expressed in a variety of tumors cells including glioma cells as well as angiogenic blood vessels. Noninvasive imaging of EphB4 could potentially increase early detection rates, monitor response to therapy directed against EphB4, and improve patient outcomes. Targeted delivery of EphB4 receptor specific peptide conjugated hollow gold nanoshells (HAuNS) into tumors has great potential in cancer imaging and photothermal therapy. In this study, we developed an EphB4 specific peptide named TNYL-RAW and labeled with radioisotope ⁶⁴Cu and Cy5.5 dye. We also conjugate this specific peptide …

Modelling Β2ar Regulation, Sharat J. Vayttaden

Dissertations and Theses (Open Access)

The β2 adrenergic receptor (β2AR) regulates smooth muscle relaxation in the vasculature and airways. Long- and Short-acting β-agonists (LABAs/SABAs) are widely used in treatment of chronic obstructive pulmonary disorder (COPD) and asthma. Despite their widespread clinical use we do not understand well the dominant β2AR regulatory pathways that are stimulated during therapy and bring about tachyphylaxis, which is the loss of drug effects. Thus, an understanding of how the β2AR responds to various β-agonists is crucial to their rational use. Towards that end we have developed deterministic models that explore the mechanism of drug- induced β2AR regulation. These mathematical models …

Change Detection Memory In Rhesus Monkeys And Humans, Lauren C. Elmore

Dissertations and Theses (Open Access)

Visual short-term memory (VSTM) is the storage of visual information over a brief time period (usually a few seconds or less). Over the past decade, the most popular task for studying VSTM in humans has been the change detection task. In this task, subjects must remember several visual items per trial in order to identify a change following a brief delay interval. Results from change detection tasks have shown that VSTM is limited; humans are only able to accurately hold a few visual items in mind over a brief delay. However, there has been much debate in regard to the …

The Role Of Tak1 In Pancreatic Cancer Development, Qianghua Xia

Dissertations and Theses (Open Access)

Pancreatic cancer is the fourth leading cause of cancer-related mortality in the United States and the fifth leading cause of cancer-related mortality worldwide. Pancreatic cancer is a big challenge in large due to the lack of early symptoms. In addition, drug resistance is a major obstacle to the success of chemotherapy in pancreatic cancer. The underlying mechanism of drug resistance in human pancreatic cancers is not well understood. Better understanding of the mechanism of molecular pathways in human pancreatic cancers can help to identify the novel therapeutic target candidates, and develop the new preventive and clinic strategies to improve patient …

Conformational Changes In The Extracellular Domain Of Glutamate Receptors, Anu Rambhadran

Dissertations and Theses (Open Access)

The family of membrane protein called glutamate receptors play an important role in the central nervous system in mediating signaling between neurons. Glutamate receptors are involved in the elaborate game that nerve cells play with each other in order to control movement, memory, and learning.

Neurons achieve this communication by rapidly converting electrical signals into chemical signals and then converting them back into electrical signals. To propagate an electrical impulse, neurons in the brain launch bursts of neurotransmitter molecules like glutamate at the junction between neurons, called the synapse. Glutamate receptors are found lodged in the membranes of the post-synaptic …

Understanding Nanog's Role In Cancer Biology, Mark D. Badeaux

Dissertations and Theses (Open Access)

Understanding Nanog’s Role in Cancer Biology

Mark Daniel Badeaux

Supervisory Professor Dean Tang, PhD

The cancer stem cell model holds that tumor heterogeneity and population-level immortality are driven by a subset of cells within the tumor, termed cancer stem cells. Like embryonic or somatic stem cells, cancer stem cells are believed to possess self-renewal capacity and the ability to give rise to a multitude of varieties of daughter cell. Because of cancer’s implied connections to authentic stem cells, we screened a variety of prostate cancer cell lines and primary tumors in order to determine if any notable ‘stemness’ genes were …

Definition Of The Landscape Of Chromatin Structure At The Frataxin Gene In Friedreich’S Ataxia, Eunah Kim

Dissertations and Theses (Open Access)

Friedreich’s ataxia (FRDA) is caused by the transcriptional silencing of the frataxin (FXN) gene. FRDA patients have expansion of GAA repeats in intron 1 of the FXN gene in both alleles. A number of studies demonstrated that specific histone deacetylase inhibitors (HDACi) affect either histone modifications at the FXN gene or FXN expression in FRDA cells, indicating that the hyperexpanded GAA repeat may facilitate heterochromatin formation. However, the correlation between chromatin structure and transcription at the FXN gene is currently limited due to a lack of more detailed analysis. Therefore, I analyzed the effects of the hyperexpanded GAA …

Dysregulation Of Meox2 Following Wt1 Mutation In Kidney Development And Wilms Tumorigenesis, Lagina M. Nosavanh, Lagina Merie Nosavanh

Dissertations and Theses (Open Access)

Wilms tumor (WT) is a childhood tumor of the kidney and a productive model for understanding the role of genetic alteration and interactions in tumorigenesis. The Wilms tumor gene 1 (WT1) is a transcriptional factor and one of the few genes known to have genetic alterations in WT and has been shown be inactivated in 20% of WTs. However, the mechanisms of how WT1 mutations lead to Wilms tumorigenesis and its influence on downstream genes are unknown. Since it has been established that WT1 is a transcriptional regulator, it has been hypothesized that the loss of WT1 leads …

The Role Of E2f1 In The Response To Dna Double Strand Breaks, Jie Chen

Dissertations and Theses (Open Access)

The importance of E2F transcription factors in the processes of proliferation and apoptosis are well established. E2F1, but not other E2F family members, is also phosphorylated and stabilized in response to various forms of DNA damage to regulate the expression of cell cycle and pro-apoptotic genes. E2F1 also relocalizes and forms foci at sites of DNA double-strand breaks but the function of E2F1 at sites of damage is still unknown. Here I reveal that E2F1 deficiency leads to increased spontaneous DNA break and impaired recovery following exposure to ionizing radiation. In response to DNA double-strand breaks, NBS1 phosphorylation and foci …

The Dissociation Of Location And Object Working Memory Using Fmri And Meg, Antony Passaro

Dissertations and Theses (Open Access)

Visual working memory (VWM) involves maintaining and processing visual information, often for the purpose of making immediate decisions. Neuroimaging experiments of VWM provide evidence in support of a neural system mainly involving a fronto-parietal neuronal network, but the role of specific brain areas is less clear. A proposal that has recently generated considerable debate suggests that a dissociation of object and location VWM occurs within the prefrontal cortex, in dorsal and ventral regions, respectively. However, re-examination of the relevant literature presents a more robust distribution suggestive of a general caudal-rostral dissociation from occipital and parietal structures, caudally, to prefrontal regions, …

The Role Of Cortisol In The Cycle Of Violence, Joshua Leigh Gowin

Dissertations and Theses (Open Access)

Child abuse and neglect are universal risk factors for delinquency, violence and aggression; this phenomenon is known as the cycle of violence. Despite a wide body of research demonstrating this phenomenon, the processes which mediate this relationship remain largely unknown. One potentially relevant result of abuse and neglect may be disruptions in the development of the body’s stress response, specifically the function of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA-axis, and its end-product, cortisol, may play a role in regulating aggressive behavior, but this function may be disrupted following abuse and neglect. Another risk factor for aggression, psychopathy, may mediate the …

Role Of The Gcn5 Histone Acetyltransferase In Spinocerebellar Ataxia Type 7 And In Immature Neurons, Yi Chun Chen

Dissertations and Theses (Open Access)

Spinocerebellar Ataxia type 7 (SCA7) is a neurodegenerative disease caused by expansion of a CAG repeat encoding a polyglutamine tract in ATXN7, a component of the SAGA histone acetyltransferase (HAT) complex. Previous studies provided conflicting evidence regarding the effects of polyQ-ATXN7 on the activity of Gcn5, the HAT catalytic subunit of SAGA. Here I showed that reducing Gcn5 expression accelerates both cerebellar and retinal degeneration in a mouse model of SCA7. Deletion of Gcn5 in Purkinje cells in mice expressing wild type Atxn7, however, causes only mild ataxia and does not lead to the early lethality observed in SCA7 mice. …

Bmp-Signaling Regulates A Common Transcriptional Program To Control Facial Form And Skeletal Morphogenesis, Margarita Bonilla-Claudio

Dissertations and Theses (Open Access)

Much of the craniofacial skeleton, such as the skull vault, mandible and midface, develops through direct, intramembranous ossification of the cranial neural crest (CNC) derived progenitor cells. Bmp-signaling plays critical roles in normal craniofacial development, and Bmp4 deficiency results in craniofacial abnormalities, such as cleft lip and palate. We performed an in depth analysis of Bmp4, a critical regulator of development, disease, and evolution, in the CNC. Conditional Bmp4 overexpression, using a tetracycline regulated Bmp4 gain of function allele, resulted in facial form changes that were most dramatic after an E10.5 Bmp4 induction. Expression profiling uncovered a signature of …

The Role Of Cell Sterilization In Population Based Studies Of Radiogenic Second Cancers Following Radiation Therapy, Annelise Giebeler

Dissertations and Theses (Open Access)

Advances in radiotherapy have generated increased interest in comparative studies of treatment techniques and their effectiveness. In this respect, pediatric patients are of specific interest because of their sensitivity to radiation induced second cancers. However, due to the rarity of childhood cancers and the long latency of second cancers, large sample sizes are unavailable for the epidemiological study of contemporary radiotherapy treatments. Additionally, when specific treatments are considered, such as proton therapy, sample sizes are further reduced due to the rareness of such treatments. We propose a method to improve statistical power in micro clinical trials. Specifically, we use a …

The Expression Profile Of A Gwas Detected Gene (Ninj2) In The Brain Of A Mouse Model Of Ischemic Stroke, Antonio Joel Tito Jr., Antonio Joel Tito Jr.

Dissertations and Theses (Open Access)

Stroke is the third leading cause of death and a major debilitating disease in the United States. Multiple factors, including genetic factors, contribute to the development of the disease. Genome-wide association studies (GWAS) have contributed to the identification of genetic loci influencing risk for complex diseases, such as stroke. In 2010, a GWAS of incident stroke was performed in four large prospective cohorts from the USA and Europe and identified an association of two Single Nucleotide Polymorphisms (SNPs) on chromosome 12p13 with a greater risk of ischemic stroke in individuals of European and African-American ancestry. These SNPs are located 11 …

Roles For Braf Kinase Activating Mutations In Melanoma: Microenvironmental Immunosuppression, Jahan Khalili

Dissertations and Theses (Open Access)

The BRAF oncogene demonstrates a characteristic mutation (V600E) in a significant fraction of cutaneous melanomas, leading to constitutive activation of the MAP kinase pathway. This genetic lesion endows tumor cells with proliferative and survival advantages, and metastatic melanoma patients treated with the BRAF(V600E)-specific inhibitor, Vemurafenib, have shown dramatic clinical responses. Here, I show that BRAF(V600E) induces transcription of the IL-1α and IL-1β genes in both melanocytes and melanoma cell lines and that this upregulation is specifically abrogated by targeted BRAF(V600E) inhibitors. Furthermore, treatment of melanoma tumor-associated fibroblasts (TAFs) with IL-1α/β significantly enhanced the ability of TAFs to suppress the proliferation …

The Cytoplasmic Tail Of Mhc Class I Molecules Plays A Critical Role In Dendritic Cell-Induced T Cell Immunity, Tania G. Rodriguez-Cruz

Dissertations and Theses (Open Access)

The presentation of MHC class I (MHC-I)/peptide complexes by dendritic cells (DCs) is critical for the maintenance of central tolerance to self and for the regulation of cytotoxic T lymphocytes (CTL)-mediated adaptive immune responses against pathogens and cancer cells. Interestingly, several findings have suggested that the cytoplasmic tail of MHC class I plays a functional role in the regulation of CTL immune responses. For example, our previous studies demonstrated that exon 7-deleted MHC-I molecules not only showed extended DC cell surface half-lives but also induced significantly increased CTL responses to viral challange invivo. Although exon 7-deleted variant of MHC-I does …

Lsuhsc Facilities Daily Updates: December 2011, Lsuhsc Property And Facilities Management

LSUHSC Facilities Daily Updates: 2011

LSUHSC Facilities Daily Updates from December 2011.

These updates describe damage and a timeline of repairs at the LSU Health Sciences Center - New Orleans campus due to Hurricane Katrina which made landfall August 29, 2005.

Reclaiming The Legal Fiction Of Congressional Delegation, Lisa Schultz Bressman

Vanderbilt Law School Faculty Publications

The framework for judicial review of agency statutory interpretations is based on a legal fiction – namely, that Congress intends to delegate interpretive authority to agencies. Critics argue that the fiction is false because Congress is unlikely to think about the delegation of interpretive authority at all, or in the way that the Court imagines. They also contend that the fiction is fraudulent because the Court does actually care about whether Congress intends to delegate interpretive authority in any particular instance, but applies a presumption triggered by statutory ambiguity or a particularized analysis involving factors unrelated to congressional delegation. In …

To Dollars From Sense: Qualitative To Quantitative Translation In Jury Damage Awards, Valerie P. Hans, Valerie F. Reyna

Cornell Law Faculty Publications

This article offers a new multistage account of jury damage award decision making. Drawing on psychological and economic research on judgment, decision making, and numeracy, the model posits that jurors first make a categorical gist judgment that money damages are warranted, and then make an ordinal gist judgment ranking the damages deserved as low, medium, or high. They then construct numbers that fit the gist of the appropriate magnitude. The article employs data from jury decision-making research to explore the plausibility of the model.

The Prospector, December 1, 2011, Utep Student Publications

The Prospector

Headline: Good Luck Graduating Miners

Influence Of Pavement Type On Near Surface Air Temperature, David Duncan

All Theses

Effects from an Urban Heat Island (UHI) can be detrimental to the world as a whole. This study examines a collection of permeable and conventional pavements in South Carolina to determine how they relate to near surface air temperatures, which is an indicator of the UHI impact of an area. Three locations were used, each with a different selection of pavement type. Permeable and conventional forms of both asphalt and concrete were tested, as were some open graded friction course samples. Air temperatures were measured and recorded from the pavement surface up to an elevation of 60-in.
Multiple days of …

Salud Y Saludos: The E-News Of The College Of Health Sciences, College Of Health Sciences

College of Health Sciences

Monthly e-newsletter of the College of Health Sciences.

Abortion, Income, Wantedness: Evidence From The American Community Survey, Francisco Arceo

All Theses

This paper serves two purposes: (1) to find the effect of the legalization of abortion on future wages and (2) to test Donohue-Levitt's 'Wantedness Hypothesis' (i.e., that relatively more wanted children have superior economic outcomes). Non-parametric evidence suggests that the legalization of abortion increased the annual salary and wage and salary income for people born before 1973 in a state with legal abortion. The OLS specifications suggest that once state surveyed and state of birth effects are included into the models the effect is negative. Once macroeconomic and other unobservable effects are controlled for, I find no evidence of an …

Short Remarks On The Political And Social Writings Of Reverend Anthony Walke Of Princess Anne County, Virginia & A Concise & Impartial Account Of The Causes Of Their Origins & Progress, Roberta Vogt

All Theses

The following thesis examines multiple social and political topics in the largely unstudied writings of Reverend Anthony Walke (c. 1755-1814) of Princess Anne County, Virginia. His papers reside at the Filson Historical Society in Louisville, Kentucky, as well as appearing in Virginia newspapers of the period. Walke's works comprise more than four hundred pages of primary source documents that relate to late eighteenth-century Virginia, and span the period of 1786 through 1805.
My research emphasizes his Revolutionary War pamphlet, Remarkable Occurrences during the unhappy American War, & a concise & impartial Account of the Causes of its Origin & Progress: …

Prevention Of Iron- And Copper-Mediated Oxidative Dna Damage By Neurotransmmitters And Related Compounds: Evidence For Metal Binding As An Antioxidant Mechanism, Carla Garcia

All Theses

An array of health concerns have been attributed to oxidative DNA damage from the hydroxyl radical (*OH), and the presence of the most biologically available metals iron and copper perpetuate the production of this radical through the Fenton and Fenton-like reactions, respectively. The concentrations at which flavonol and polyphenol antioxidants prevent 50% of DNA damage (IC50) were measured using gel electrophoresis assays upon Fe(II)/H2O2- and Cu(I)/H2O2-mediated DNA damage (Chapter 2). Results show that catechol- and gallol-containing antioxidants differ greatly in preventing DNA damage by Cu(I)/H2O2, compared to Fe(II)/H2O2, behavior that was explained using electron paramagnetic resonance spectroscopy. Semiquinone and other …