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This Is Just A Phase : The Impact Of Population Structure On Haplotype Phasing And Linkage Disequilibrium Measures At Functional Genetic Sites., Roxanne Kaaren Leiter Dec 2017

This Is Just A Phase : The Impact Of Population Structure On Haplotype Phasing And Linkage Disequilibrium Measures At Functional Genetic Sites., Roxanne Kaaren Leiter

Electronic Theses and Dissertations

The block-like structure of the human genome has been the subject of many scientific papers and is of practical significance in large-scale genome-wide association studies. How stringent haplotype block boundaries are within and between populations has been the subject of ongoing debate within human population genetics. This thesis will contribute to the description of universal and population-specific haplotype blocks at functional sites, namely across the IL-10 gene family (including IL-10, IL-19, IL-20 and IL-24), which is involved in a number of immune system processes, and MAPKAP-K2, an adjacent and functionally significant kinase gene. Beyond the description of blocks across these …


Functional Data Analysis Methods For Predicting Disease Status., Sarah Kendrick Dec 2017

Functional Data Analysis Methods For Predicting Disease Status., Sarah Kendrick

Electronic Theses and Dissertations

Introduction: Differential scanning calorimetry (DSC) is used to determine thermally-induced conformational changes of biomolecules within a blood plasma sample. Recent research has indicated that DSC curves (or thermograms) may have different characteristics based on disease status and, thus, may be useful as a monitoring and diagnostic tool for some diseases. Since thermograms are curves measured over a range of temperature values, they are often considered as functional data. In this dissertation we propose and apply functional data analysis (FDA) techniques to analyze DSC data from the Lupus Family Registry and Repository (LFRR). The aim is to develop FDA methods to …


Type Ix Secretion System : Characterization Of An Effector Protein And An Insight Into The Role Of C-Terminal Domain Dimeration In Outer Membrane Translocation., Lahari Koneru Dec 2017

Type Ix Secretion System : Characterization Of An Effector Protein And An Insight Into The Role Of C-Terminal Domain Dimeration In Outer Membrane Translocation., Lahari Koneru

Electronic Theses and Dissertations

Porphyromonas gingivalis and Tannerella forsythia are two of the primary pathogens that are associated in the etiology and progression of chronic periodontitis. In T. forsythia, KLIKK proteases are the recently identified group of proteolytic enzymes that are secreted through Type IX secretion system (T9SS). Among, these KLIKK proteases a synergistic relationship was observed between karilysin and mirolysin in invading the host complement system for the survival of the bacteria. Since, karilysin has been already characterized, in this study we propose to study about mirolysin through structural, biochemical and biological characterization. The obtained results from the experiments has shown the …


Age-Related Host Factors Regulate Lung Cancer Progression., John Caleb Greenwell Dec 2017

Age-Related Host Factors Regulate Lung Cancer Progression., John Caleb Greenwell

Electronic Theses and Dissertations

Cancer is largely a disease of the elderly. In the United States alone, 87% of all cancers in 2017 will be diagnosed in individuals aged 50 years or older. Among them, lung cancer is the deadliest, accounting for 1 in 4 cancer deaths. The 5-year survival rate is below 20%, a number which has not changed substantially over the past several decades. This underscores a desperate need for new strategies in prevention, early detection and treatment of this deadly disease. While tobacco use is unquestionably the number one risk factor for the development of lung cancer, the majority of diagnoses …


Nonspreading Solutions In Integro-Difference Models With Allee And Overcompensation Effects., Garrett Luther Otto Dec 2017

Nonspreading Solutions In Integro-Difference Models With Allee And Overcompensation Effects., Garrett Luther Otto

Electronic Theses and Dissertations

Previous work in Integro-Difference models have generally considered Allee effects and over-compensation separately, and have either focused on bounded domain problems or asymptotic spreading results. Some recent results by Sullivan et al. (2017 PNAS 114(19), 5053-5058) combining Allee and over-compensation in an Integro-Difference framework have shown chaotic fluctuating spreading speeds. In this thesis, using a tractable parameterized growth function, we analytically demonstrate that when Allee and over-compensation are present solutions which persist but essentially remain in a compact domain exist. We investigate the stability of these solutions numerically. We also numerically demonstrate the existence of such solutions for more general …


The Dlk1-Meg3 Locus In Malignant Cells Of Proposed Primordial Germ Cell Origins., Zachariah Payne Sellers Aug 2017

The Dlk1-Meg3 Locus In Malignant Cells Of Proposed Primordial Germ Cell Origins., Zachariah Payne Sellers

Electronic Theses and Dissertations

Primordial germ cells (PGCs) are hypothesized to deposit hematopoietic stem cells (HSCs) along their migration route through the embryo during the early stages of embryogenesis. PGCs also undergo global chromatin remodeling, including the erasure and reestablishment of genomic imprints, during this migration. While PGCs do not spontaneously form teratomas, their malignant development into germ cell tumors (GCTs) in vivo is often accompanied by the retention of hypomethylation at the IGF2-H19 imprinting control differentially methylated region (DMR). Previous studies in bimaternal embryos determined that proper genomic imprinting at two paternally imprinted loci was necessary for their growth and development: Igf2-H19 and …


Characterization Of Filifactor Alocis And Its Immune Evasion Strategies Employed Against Human Neutrophils., Cortney Linn Armstrong Aug 2017

Characterization Of Filifactor Alocis And Its Immune Evasion Strategies Employed Against Human Neutrophils., Cortney Linn Armstrong

Electronic Theses and Dissertations

Periodontal disease is among the most common of inflammatory conditions and is caused by bacterial and host derived factors. The presence of bacteria drives the recruitment of neutrophils, professional phagocytes, to migrate to specific oral sites where they produce potent antimicrobials to kill their target. However, this inflammation and production of antimicrobials must be strictly regulated to minimize collateral host tissue damage. Human neutrophils recognized the oral pathogen Filifactor alocis through Toll-like receptor (TLR) 2 and upon binding, activated both p38 MAPK and ERK signaling pathways, known to be involved in neutrophil cell migration and degranulation. F. alocis also stimulated …


Characterizing Reactive Glutamines In Fibrinogen And Elucidating Factor Xiii Substrate Specificity., Kelly Njine Mouapi Aug 2017

Characterizing Reactive Glutamines In Fibrinogen And Elucidating Factor Xiii Substrate Specificity., Kelly Njine Mouapi

Electronic Theses and Dissertations

Fibrinogen is the most abundant protein involved in blood coagulation and has been associated with many pathological implications in cardiovascular disease. At the final stages of blood clot formation, the transglutaminase Factor XIIIa introduces γ-glutamyl-ε-lysinyl covalent bonds between reactive glutamines and lysines in fibrin, which results in a tighter clot network that is resistant to fibrinolysis. Factor XIIIa crosslinks specific reactive glutamines on fibrinogen, selecting more reactive glutamines in the αC region of fibrinogen than any other chain. Although crosslinking pairs in the αC region have been identified, little is known about the extent of crosslinking and the role played …


Regulation Of Haplid Phenotypes In Ustilago Maydis By Ammonium Transporters And Components Of The B Mating Locus., Rena Margaret Wallen Aug 2017

Regulation Of Haplid Phenotypes In Ustilago Maydis By Ammonium Transporters And Components Of The B Mating Locus., Rena Margaret Wallen

Electronic Theses and Dissertations

Fungi that can switch from budding to a filamentous infectious state have evolved mating type loci. Ustilago maydis, the maize pathogen, must mate with compatible partners possessing different alleles at two mating type loci for successful host infection. The a locus encodes pheromones and receptors, while the b locus encodes subunits of a heterodimeric transcription factor that regulates expression of virulence genes. Mating is triggered by environmental signals, including nutrient deprivation. My goal was to determine the fate of nitrogen starved haploid cells without a compatible mating partner. On solid low ammonium media, wild-type U. maydis filaments. I examined …


Mitochondrial Transcription Factor A'S Role In Heart Failure., George H. Kunkel Aug 2017

Mitochondrial Transcription Factor A'S Role In Heart Failure., George H. Kunkel

Electronic Theses and Dissertations

Background: An essential mitochondrial component, Mitochondrial Transcription Factor A (TFAM) is reduced within the failing heart. TFAM maintains regulatory functions of cardiomyocyte physiology and stability. Mitochondrial Transcription Factor A forms a mitochondrial nucleoid anti-oxidant structure and reduces pathophysiological abnormalities to structural and contractile proteins. Overall, this functions to physically stabilize mtDNA. Significant molecular changes such as a loss of TFAM drive pathophysiological concentrations of cytoplasmic Ca2+ and reactive oxygen species. Both of these factors induce proteolytic enzymes to degrade the physiological cardiomyocyte. In TFAMs absence, heart function deteriorates and hypertrophic expansion ensues: thereby changing the physiological myocardium to a pathological …


Algorithms For Automated Assignment Of Solution-State And Solid-State Protein Nmr Spectra., Andrey Smelter Aug 2017

Algorithms For Automated Assignment Of Solution-State And Solid-State Protein Nmr Spectra., Andrey Smelter

Electronic Theses and Dissertations

Protein nuclear magnetic resonance spectroscopy (Protein NMR) is an invaluable analytical technique for studying protein structure, function, and dynamics. There are two major types of NMR spectroscopy that are used for investigation of protein structure – solution-state and solid-state NMR. Solution-based NMR spectroscopy is typically applied to proteins of small and medium size that are soluble in water. Solid-state NMR spectroscopy is amenable for proteins that are insoluble in water. In the vast majority NMR-based protein studies, the first step after experiment optimization is the assignment of protein resonances via the association of chemical shift values to specific atoms in …


Mechanism Investigation Of Pseudouridine Synthases Trub And Rlua With Rna Containing 5-Fluorouridine And 4-Thiouridine., Uyen T. Duong Aug 2017

Mechanism Investigation Of Pseudouridine Synthases Trub And Rlua With Rna Containing 5-Fluorouridine And 4-Thiouridine., Uyen T. Duong

Electronic Theses and Dissertations

Pseudouridine synthases (Ψ synthases) are the enzymes that catalyze the isomerization of uridine (U) to pseudouridine (Ψ), which is the most prevalent post-transcriptional modification of RNA. The Ψ synthases fall into six different families that share no significant global sequence similarity; however, they all involve a conserved aspartic acid residue which is absolutely essential for activity. Tyrosine is a conserved residue in the active site in five of the six families of Ψ synthases (phenylalanine in the TruD family) and was hypothesized as the general base for the isomerization reaction. To confirm the function of Tyr-96, Y96F RluA was assayed …


Circuits For Active Vision : Parallel Tectothalamocortical Visual Pathways In The Mouse., Na Zhou Aug 2017

Circuits For Active Vision : Parallel Tectothalamocortical Visual Pathways In The Mouse., Na Zhou

Electronic Theses and Dissertations

Vision is a critical sensation for the interaction between humans and their surrounding environment. The eyes connect with the brain via retinal ganglion cell axons, which transmit visual sensory information from the periphery into the central nervous system for further processing, eventually leading to visual perception and the visual guidance of movement. Two main targets of retinal axons are the superior colliculus (SC) and the dorsal thalamus. From the SC, visual information is conveyed to the dorsal thalamus, and from the dorsal thalamus visual information is conveyed to the cortex, striatum and amygdala. This dissertation is focused on the functional …


Novel Insight Into The Liver-Lung Axis In Alcohol-Enhanced Acute Lung Injury., Lauren G. Poole Aug 2017

Novel Insight Into The Liver-Lung Axis In Alcohol-Enhanced Acute Lung Injury., Lauren G. Poole

Electronic Theses and Dissertations

Background. Individuals who chronically abuse alcohol are almost 4 times more likely to develop Acute Respiratory Distress Syndrome (ARDS), the most severe form of Acute Lung Injury (ALI), but the mechanisms by which alcohol abuse sensitizes the lung to injury are poorly understood. However, the lung appears to share many parallel mechanisms of injury with the liver- a primary target of alcohol abuse. The overarching goal of this dissertation was therefore to expand on established mechanisms of alcohol-induced liver injury to ask innovative questions about mechanisms of alcohol-enhanced acute lung injury, as well as to develop new tools that may …


Advances In Tumor-Targeted Therapy Using Nanomedicine., Divya Karukonda Aug 2017

Advances In Tumor-Targeted Therapy Using Nanomedicine., Divya Karukonda

Electronic Theses and Dissertations

Despite continuous improvement and significant progress made in diagnostic and therapeutic approaches for cancer, it is still the leading cause of death worldwide. Although conventional chemotherapy has made significant advances in improving patient survival the indiscriminate destruction of normal cells leads to severe side effects and poor clinical outcomes. Thus, there is a need for effective delivery of drugs to the tumor site avoiding normal tissues to reduce toxicity in the rest of the body. For this reason, a novel multidisciplinary field called Nanotechnology has evolved in recent years and advances in this field have contributed to the development of …


Prevention And Treatment Of Familial Adenomatous Polyposis And Colorectal Cancer By Bilberry-Derived Anthocyanidins., Ashley M. Mudd Aug 2017

Prevention And Treatment Of Familial Adenomatous Polyposis And Colorectal Cancer By Bilberry-Derived Anthocyanidins., Ashley M. Mudd

Electronic Theses and Dissertations

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths within the United States. Familial adenomatous polyposis (FAP) is an inherited disorder which if left untreated will develop into colon cancer. The family of plant-derived compounds, anthocyanins, show significant therapeutic potential against a variety of diseases, however, they are limited by their instability and poor bioavailability. The goal of my Master’s research project was to determine whether anthocyanidins (non-glycosylated anthocyanins) are more effective than the native anthocyanins, and whether exosomal formulation of anthocyanidins (ExoAnthos) can enhance therapeutic potency compared with free Anthos against both FAP and CRC. The antiproliferative …


The Comparative Cytotoxicity And Genotoxicity Of Hexavalent Chromium In Humans And Sea Turtles., Rachel M. Speer Aug 2017

The Comparative Cytotoxicity And Genotoxicity Of Hexavalent Chromium In Humans And Sea Turtles., Rachel M. Speer

Electronic Theses and Dissertations

Monitoring the health effects of environmental contaminants can be achieved using sentinel species as models. Leatherback sea turtles (Dermochelys coriacea) are an endangered marine species that may experience prolonged exposures to environmental contaminants including hexavalent chromium [Cr(VI)]. While Cr(VI) has been identified as a known human carcinogen, the health effects in marine species are poorly understood. In this study the cytotoxic and genotoxic effects of particulate and soluble Cr(VI) were assessed in leatherback lung cells and compared to those in human lung cells. Cr(VI) induced a concentration-dependent increase in cytotoxicity and genotoxicity in leatherback lung cells indicating Cr(VI) …


Sphingolipids In Models Of Kidney Disease And Injury., Tess V. Dupre Aug 2017

Sphingolipids In Models Of Kidney Disease And Injury., Tess V. Dupre

Electronic Theses and Dissertations

Acute kidney injury (AKI), resulting from cisplatin, remains an obstacle in the treatment of cancer. Cisplatin-induced AKI involves cell death pathways regulated by sphingolipids such as ceramide and glucosylceramide. Results indicate that cisplatin-treated mice had increased levels of ceramide and hexosylceramide. Pre-treatment of mice with inhibitors of ceramide synthesis prevented accumulation of ceramide and hexosylceramide in the renal cortex and attenuated cisplatin-induced AKI. To determine the role of ceramide metabolism to hexosylceramides in kidney injury, we treated mice with an inhibitor of glycosphingolipid synthesis. Inhibition of glycosphingolipid synthesis attenuated the accumulation of the hexosylceramide and exacerbated ceramide accumulation in the …


Porphyromonas Gingivalis Infection In Gestational Diabetes Mellitus And Survival In Tobacco Smokers., Himabindu Gogeneni Aug 2017

Porphyromonas Gingivalis Infection In Gestational Diabetes Mellitus And Survival In Tobacco Smokers., Himabindu Gogeneni

Electronic Theses and Dissertations

This thesis contains a clinical project and distinct basic science project. Gestational diabetes mellitus occurs in 4% of pregnancies and increases the risk of birth defects, pre-term birth, and miscarriage. Gingivitis during pregnancy also increases the risk for poor pregnancy outcome. Gingivitis is a bacterial-induced disease, and specific plaque pathogens have been associated with systemic sequelae to periodontal inflammation. Therefore, we set out to monitor oral infection with three key periodontopathogens (Porphyromonas gingivalis, Filifactor alocis, and Treponema denticola) and the systemic inflammatory burden [C-reactive protein (CRP) in pregnant women with and without gingivitis and gestational diabetes. Gingivitis …


Targeting Fas Pathway As An Effective Means Of Inducing Tolerance To Pancreatic Islets., Kyle Blake Woodward Aug 2017

Targeting Fas Pathway As An Effective Means Of Inducing Tolerance To Pancreatic Islets., Kyle Blake Woodward

Electronic Theses and Dissertations

Signaling through Fas/FasL is critical to immune homeostasis and tolerance to self-antigens. SA-FasL is a chimeric protein of FasL and streptavidin. SA-FasL exists as oligomers with potent apoptotic function on Fas expressing immune cells and tightly binds to biotinylated surfaces. Islet grafts engineered to transiently display SA-FasL on their surface established tolerance in allogeneic recipients with a short course of rapamycin. We hypothesized that SA-FasL on the islet allograft will induce apoptosis in alloreactive T effector (Teff) cells and phagocytes clearing apoptotic bodies will produce tolerogenic molecules, such as TGF-β, that will lead to the generation and/or expansion of Treg …


Characterization Of Porphyromonas Gingivalis Mfa1 Fimbriae., Jae Yong Lee Aug 2017

Characterization Of Porphyromonas Gingivalis Mfa1 Fimbriae., Jae Yong Lee

Electronic Theses and Dissertations

Porphyromonas gingivalis, an obligate anaerobic bacterium associated with chronic periodontitis, utilizes various virulence factors to achieve pathogenicity, one of which is the Mfa1 fimbriae. As a surface structure comprising Mfa1 major subunit along with accessory fimbrial proteins Mfa2-5, the Mfa1 fimbriae has been shown to mediate the adherence of P. gingivalis to antecedent bacterial colonizers of the oral cavity to cause increased virulence. However, the spatial relationships amongst the individual subunits and their assembly mechanism have remained unclear. Through immuno-electron microscopy, Mfa1-4 were localized on the surface of P. gingivalis with Mfa1 localizing throughout the fimbriae and Mfa2 in …


Gene Expression Of Ammonium Transporters In Ustilago Maydis And Their Role In Pathogenicity And Virulence., Kirsten Richardson Aug 2017

Gene Expression Of Ammonium Transporters In Ustilago Maydis And Their Role In Pathogenicity And Virulence., Kirsten Richardson

Electronic Theses and Dissertations

The fungus, Ustilago maydis, a plant pathogen of Zea mays, is capable of a dimorphic switch, e.g., a transition between a yeast-like form and a filamentous form. This switch is activated when U. maydis cells are starved for their preferred nitrogen source - ammonium. U. maydis has two important genes that play a role in this switch, ump1 and ump2. Each gene is responsible for the uptake of ammonium and the latter is responsible for the filamentous response in the absence of ammonium. Ump2 deletion mutants are unable to filament in response to low ammonium while ump1 deletion …


Social Dynamics, Network Structure, And Information Diffusion In Fish Shoals., Matthew Jerome Hasenjager May 2017

Social Dynamics, Network Structure, And Information Diffusion In Fish Shoals., Matthew Jerome Hasenjager

Electronic Theses and Dissertations

Animal populations are often highly structured, with individuals differing in terms of whom they interact with and how frequently they do so. The resulting pattern of relationships constitutes a population’s social network. In this dissertation, I examine how environmental variation can shape social networks and influence information flow within them. In Chapter I, I review the history of social network analysis in animal behavior research, and discuss recent insights generated by network approaches in behavioral ecology. I focus on the fields of: social learning, collective behavior, animal personalities, and cooperation. Animal network studies are often criticized for a lack of …


Novel Statistical Approaches For Missing Values In Truncated High-Dimensional Metabolomics Data With A Detection Threshold., Jasmit Sureshkumar Shah May 2017

Novel Statistical Approaches For Missing Values In Truncated High-Dimensional Metabolomics Data With A Detection Threshold., Jasmit Sureshkumar Shah

Electronic Theses and Dissertations

Despite considerable advances in high throughput technology over the last decade, new challenges have emerged related to the analysis, interpretation, and integration of high-dimensional data. The arrival of omics datasets has contributed to the rapid improvement of systems biology, which seeks the understanding of complex biological systems. Metabolomics is an emerging omics field, where mass spectrometry technologies generate high dimensional datasets. As advances in this area are progressing, the need for better analysis methods to provide correct and adequate results are required. While in other omics sectors such as genomics or proteomics there has and continues to be critical understanding …


Exploring A Novel Nf-ĸb- Inhibiting Nanoparticle For Periodontitis Therapy., Kameswara Satya Srikanth Upadhyayula May 2017

Exploring A Novel Nf-ĸb- Inhibiting Nanoparticle For Periodontitis Therapy., Kameswara Satya Srikanth Upadhyayula

Electronic Theses and Dissertations

Periodontitis is an infection-driven inflammatory disease characterized by gingival inflammation and bone loss. The NF-ĸB signaling pathway is pivotal in osteoclastogenesis and infection-induced pro-inflammatory responses. The use of nanoparticles as a vehicle to deliver drug increases stability, loading capacity, and facilitates transmembrane transportation. The hypothesis was that a novel nanoparticle carrying therapeutic NBD inhibitory peptides (NBD-nanoparticles) will inhibit measures of periodontal disease. In this project, we tested the nanoparticles for their ability to directly inhibit osteoclastogenesis and inflammation as an original strategy for periodontitis therapy. We also tested the capability of the nanoparticles to inhibit gingival inflammation and alveolar bone …


Environmental Factors, Not Plants, Contribute To Functional Diversity Of Soil Bacteria In The Dunes Of Lake Michigan., Andrea Stark Howes May 2017

Environmental Factors, Not Plants, Contribute To Functional Diversity Of Soil Bacteria In The Dunes Of Lake Michigan., Andrea Stark Howes

Electronic Theses and Dissertations

Soil bacteria play important roles in nutrient cycling and other ecosystem functions, and many biotic and abiotic factors can influence bacterial functional diversity. The goal of this field study was to examine differences among bacterial communities in sand dunes of Lake Michigan. I used Biolog Ecoplates™ to compare bacteria functional diversity associated with four different plant species: the native dune-building grass Ammophila breviligulata, invasive species Leymus arenarius and Gypsophila paniculata, and native legume Lathyrus japonicus across 13 sites in Michigan, representing a gradient in abiotic factors such as precipitation and temperature. I found no differences in bacterial function associated with …


Intraspecific Differences In Belowground Associations And Seedling Root Morphology For The Biofuel Crop, Panicum Virgatum., Erin Renee Kinnetz May 2017

Intraspecific Differences In Belowground Associations And Seedling Root Morphology For The Biofuel Crop, Panicum Virgatum., Erin Renee Kinnetz

Electronic Theses and Dissertations

The perennial C4 grass Panicum virgatum (switchgrass) is a promising bioenergy feedstock. Switchgrass is symbiotic with arbuscular mycorrhizal fungi (AMF). I examined 12 varieties of switchgrass grouped into 2 ecotypes (upland, lowland) to see if they differed in AMF abundance and root colonization using the GLBRC Variety Trials experiment. There was higher root colonization of lowland ecotype. A greenhouse experiment evaluated the role of live soil organisms in seedling establishment of 11 varieties. Live soil increased seedling survival, growth and influenced root morphology. Ecotypes differed in root architecture. Lowland developed a higher specific root length (SRL), a trait associated …


Enhancing Cell Therapy For Ischemic Cardiomyopathy., Michael J. Book May 2017

Enhancing Cell Therapy For Ischemic Cardiomyopathy., Michael J. Book

Electronic Theses and Dissertations

Cardiac cell therapy using cardiac mesenchymal cells (CMC) significantly reduces ventricular dysfunction in patients with ischemic cardiomyopathy. Despite the improvement in function, a modest number of CMCs survive in the heart post-transplantation. In this study, we sought to improve the survival and retention of transplanted CMCs to prolong the therapeutic benefits afforded by cardiac cell therapy. To do this, we targeted the enzyme telomerase (TERT), known to be active in some highly proliferating cells (e.g. germ, stem). TERT is responsible for preventing telomere attrition, thereby allowing continued proliferation. TERT has also been shown to be protective, improve cell migration and …


Role Of Mir-29b-1 And Mir-29a In Endocrine-Resistant Breast Cancer., Penn Muluhngwi May 2017

Role Of Mir-29b-1 And Mir-29a In Endocrine-Resistant Breast Cancer., Penn Muluhngwi

Electronic Theses and Dissertations

Therapies targeting estrogen receptor α (ERα) including selective estrogen receptor modulators (SERMs), e.g., tamoxifen (TAM); selective estrogen receptor downregulators (SERDs), e.g., fulvestrant (ICI 182,780); and aromatase inhibitors (AI), e.g., letrozole, are successfully used in treating breast cancer patients whose initial tumor expresses ERα. Unfortunately, the effectiveness of endocrine therapies is limited as ~ 40% of breast cancer patients will eventually acquire resistance to them. The role of miRNAs in the progression of endocrine-resistant breast cancer is of keen interest in developing biomarkers and therapies to counter metastatic disease. This dissertation begins with a review on miRNAs implicated …


Identifying The Signaling Mechanisms Of Egfr-Mediated Apoptosis., Nicole Marion Jackson May 2017

Identifying The Signaling Mechanisms Of Egfr-Mediated Apoptosis., Nicole Marion Jackson

Electronic Theses and Dissertations

The Epidermal Growth Factor Receptor (EGFR) is a 170-kilodalton transmembrane protein that belongs to the ErbB family of receptor tyrosine kinases. Upon ligand-mediated activation, the EGFR is responsible for cell growth, proliferation, and tissue homeostasis; however, the EGFR is overexpressed in many human malignancies, including MDA-MB-468 cells, a metastatic breast epithelial cell line. Studies within this cell line, and other cell lines characterized with high EGFR levels, have shown that EGF stimulation results in the induction of apoptosis. However, the mechanisms and signaling effectors implicated in this process have yet to be elucidated. The overarching research goal of this dissertation …