Medicine and Health Sciences Commons^™

Genomic Drivers Of Cutaneous Squamous Cell Carcinoma Development, Vida Chitsazzadeh

Dissertations and Theses (Open Access)

Skin cancer is the most common malignancy in humans. Annually, in U.S. there are over 3 million cases with an estimated overall economic impact of $2 billion. Cutaneous Squamous Cell Carcinoma (cuSCC) comprises 15-20% of all skin cancers. cuSCC has the best-defined progression from a distinct precancerous lesion, the Actinic Keratosis (AK), to invasive cuSCC. Destructive therapies for AK treatment must be used repetitively, causing significant morbidity. There is a tremendous need for targeted diagnostics and therapy for AKs, representing an important opportunity for secondary skin cancer prevention. Our knowledge of the molecular and cellular events that lead to the …

Insights Into Determinants That Contribute To Colonization, Virulence And Antibiotic Resistance In Enterococci, Maria Camila Montealegre

Dissertations and Theses (Open Access)

Enterococcus faecalis and Enterococcus faecium are increasingly common as causative agents of human infections, many of which are very difficult to treat due to multi-drug resistance. The work presented in the first part of this dissertation elucidates a mechanism for the regulation of pilus expression. I showed that ATT is the initiation codon of ebpA, the first gene of an operon that codes for the endocarditis and biofilm-associated pili (Ebp), a recognized virulence factor in E. faecalis. The presence of this rare start codon downregulates EbpA translation and protein levels, diminishing biofilm and binding abilities of …

Developing And Using Methyl-Specific Antibodies To Study The Biological Roles Of Arginine Methylation, Vidyasiri Vemulapalli

Dissertations and Theses (Open Access)

Arginine residues can be modified in three different ways to produce asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and monomethylarginine (MMA). These modifications are catalyzed by a family of nine protein arginine methyltransferases (PRMT1-9), which are of three types (I, II, and III). The majority of Type I enzymes asymmetrically dimethylate Glycine- and Arginine-rich (GAR) motifs, except for PRMT4, which methylates Proline-, Glycine-, and Methionine-rich (PGM) motifs. The same substrates (GAR or PGM motifs) can also be dimethylated by PRMT5 in a symmetric fashion. However, it is not clear whether there are dedicated residues within these motifs for ADMA and SDMA, …

Network Dynamics Of Visual Object Recognition, Mehmet C. Kadipasaoglu

Dissertations and Theses (Open Access)

Visual object recognition is the principal mechanism by which humans and many animals interpret their surroundings. Despite the complexity of neural computation required, object recognition is achieved with such rapidity and accuracy that it appears to us almost effortless. Extensive human and non-human primate research has identified putative category-selective regions within higher-level visual cortex, which are thought to mediate object recognition. Despite decades of study, however, the functional organization and network dynamics within these regions remain poorly understood, due to a lack of appropriate animal models as well as the spatiotemporal limitations of current non-invasive human neuroimaging techniques (e.g. fMRI, …

Poly (Adp) Ribose Polymerase Inhibitors For The Treatment Of Malignant Peripheral Nerve Sheath Tumor, Christine M. Kivlin

Dissertations and Theses (Open Access)

Malignant peripheral nerve sheath tumor (MPNST) is a rare subtype of soft tissue sarcoma. Surgical excision has remained the standard of care for this highly aggressive malignancy for over a decade. Conventional chemotherapy and radiotherapy have shown limited efficacy in MPNST; therefore, it is imperative that targeted treatment be identified to improve the outcome for MPNST patients. Poly (ADP) ribose polymerase (PARP) inhibitors were first reported over a decade ago to have substantial anti-tumorigenic effects in malignancies with defective DNA repair, specifically those with BRCA1/2 (breast cancer, early onset 1/2) mutations. Further evaluation of these inhibitors has shown multiple mechanisms …

Characterization Of Stem Cell Turnover In A Living Epithelial Bilayer, Elizabeth Sumner

Dissertations and Theses (Open Access)

Homeostatic maintenance of epithelia requires the renewal and replacement of old or dying cells while sustaining a functional barrier. Imbalance between cell production and elimination are hypothesized to underlie many pathological conditions. However, our knowledge of cell turnover within living tissues remains largely restricted to static images due to the limited ability to study epithelia in their native context. Here we report that clearance of damaged basal stem cells promotes compensatory proliferation of neighboring stem cells to maintain overall population numbers in a bilayered epithelium. Time-lapse imaging and electron microscopy experiments reveal that dying cells are rapidly cleared as nearby …

No Difference In Health Related Quality Of Life Between Therapeutic Options For Type 1 Gaucher Disease, Victoria Wagner

Dissertations and Theses (Open Access)

Type 1 Gaucher disease (GD) is the most common lysosomal storage disorder. Previously, treatment for GD was limited to intravenous enzyme replacement therapy (ERT). ERT reduces symptoms and increases health­related quality of life (HRQoL) in people with this condition. In 2014, oral substrate reduction therapy (SRT) was approved for type 1 GD treatment. Although both therapies alleviate disease symptoms, effects of SRT on HRQoL and preferences for therapy are not well established. Electronic surveys were administered to adults with type 1 GD. HRQoL was scored with the Short Form­36 Version 2 ® Health Survey and descriptive statistics were used to …

The Thioredoxin Trx-1 Regulates The Major Oxidative Stress Response Transcription Factor, Skn-1, In Caenorhabditis Elegans, Katie C. Mccallum

Dissertations and Theses (Open Access)

The ability to respond to hostile environmental conditions is critical for the survival of an organism. Oxidative stress is an adverse state in which reactive oxygen species (ROS) accumulate to a harmful level and, if left unresolved, can lead to cellular dysfunction and organismal disease. Sophisticated detoxification systems, characterized by a battery of enzymatic antioxidants, are utilized to neutralize ROS thereby reducing stress. However, ROS are also purposefully produced by designated cellular enzymes to facilitate the signaling and regulation of critical physiological processes. Therefore, both the production and neutralization of ROS must be tightly controlled. Indeed, the expression of detoxification …

Factors Influencing Uptake Of Risk-Reducing Salpingo-Oophorectomy By Brca1 And Brca2 Mutation Carriers, Victoria E. Breen

Dissertations and Theses (Open Access)

Germline mutations in the BRCA1 and BRCA2 genes are associated with significantly increased risks for ovarian cancer. The National Comprehensive Cancer Network (NCCN) currently recommends that female BRCA mutation carriers undergo risk-reducing salpingo-oophorectomy (RRSO) after age 35; however, not all women elect this option. The purpose of this study was to prospectively survey women with BRCA mutations currently undergoing ovarian cancer screening about their intention to have an RRSO and the various factors influencing their decision. Of the 26 women who completed our survey, 26 (100%, CI: 86.8-100) plan to undergo an RRSO in their lifetime. The average woman reported …

The Role Of 5-Alpha Reductase 3 In Steroid Metabolism, Zahi Mitri

Dissertations and Theses (Open Access)

Background

The growth and development of prostate cancer is largely driven by androgen mediated signaling. The 5-alpha reductase family of enzymes plays an essential role in the conversion of testosterone to the more potent androgen, 5-alpha dihydrotestosterone (DHT), which is capable of binding the androgen receptor to activate gene targets and downstream signaling. This study aimed to evaluate the role of 5-alpha reductase 3 (SRD5A3), a novel member of the 5-alpha reductase family, in steroid metabolism and prostate carcinogenesis.

Materials and Methods

HEK293 cells were transfected with the SRD5A3 human cDNA ORF Clone from OriGene. Steroid substrates (testosterone, progesterone, androstenedione, …

The Roles Of Malt1 In Nf-Κb Activation And Solid Tumor Progression, Deng Pan

Dissertations and Theses (Open Access)

The transcription factor NF-κB plays a central role in many aspects of biological processes and diseases, such as inflammation and cancer. Although it has been suggested thatNF-κB is critical in tumorigenesis and tumor progression, the molecular mechanism by which NF-κB is activated in solid tumor remains largely unknown. In the current work, we focus on growth factor receptor-induced NF-κB activation and tumor progression, including epidermal growth factor receptor (EGFR)-induced NF-κB in lung cancer and heregulin receptor (HER2)-induced NF-κB in breast cancer. We found that Mucosa-associated lymphoma translocation protein 1 (MALT1), also known as paracaspase, is required for EGFR-induced NF-κB activation …

The Psychosocial Effects Of The Li-Fraumeni Education And Early Detection (Lead) Program On Indivdiuals With Li-Fraumeni Syndrome, Jessica L. Ross

Dissertations and Theses (Open Access)

Li-Fraumeni syndrome (LFS) is a hereditary cancer syndrome that leads to an increased risk of multiple cancers. In the past five years new screening protocols have been developed that provide improved screening options for individuals with LFS. However, very little has been published on the psychosocial impact of these screening protocols. The goals of this study were to determine how participation in screening impacts individuals psychosocially, to examine the benefits and drawbacks of screening, and to evaluate possible barriers to continued screening. This qualitative study consisted of phone interviews with 20 individuals that took part in an LFS screening program …

Attitudes To Wards Prenatal Genetics Among Southeast And East Asian Women: A Qualitative Pilot Study, Ginger J. Tsai

Dissertations and Theses (Open Access)

From 2000-2010, the Asian population in the United States grew five times faster than the overall US population. As Asians become incorporated into the US health care system, it is important to recognize cultural differences that may arise between Asian patients and their health care providers. Prior studies show that cultural values influence genetic perceptions within Asian populations. The reputation of the family unit factors into decisions such as pregnancy termination and disclosure of family medical history, and the non-directive model of American genetic counseling conflicts with the historical Asian model of paternalistic health care. Previous studies also provide conflicting …

Patient Perception Of Negative Non-Invasive Prenatal Testing Results, Ann Theresa Wittman

Dissertations and Theses (Open Access)

Non-invasive prenatal testing (NIPT) uses cell-free fetal DNA to assess for fetal aneuploidy during pregnancy. NIPT has higher detection rates and positive predictive values than previous methods; however, NIPT is not diagnostic. Studies suggest patients may underestimate the limitations of prenatal screening. Therefore, we conducted a prospective cross-sectional study of ninety-four women from genetic counseling clinics in Houston, Texas to assess patient understanding of the residual risk for aneuploidy after receiving a negative NIPT. The majority of participants (66%) understood the residual risk for Down syndrome following negative NIPT; however, 34% of participants indicated that negative NIPT completely eliminated the …

Accurate Mutation Annotation And Functional Prediction Enhance The Applicability Of -Omics Data In Precision Medicine, Tenghui Chen

Dissertations and Theses (Open Access)

Clinical sequencing has been recognized as an effective approach for enhancing the accuracy and efficiency of cancer patient management and therefore achieve the goals of personalized therapy. However, the accuracy of large scale sequencing data in clinics has been constrained by many different aspects, such as clinical detection, annotation and interpretation of the variants that are observed in clinical sequencing data. In my Ph.D thesis work, I mainly investigated how to comprehensively and efficiently apply high dimensional -omics data to enhance the capability of precision cancer medicine. Following this motivation, my dissertation has been focused on two important topics in …

Cll Metabolism Is Regulated By Prognostic Factors, Modulated By Stroma And Abrogated By Pi3k Inhibition, Hima Vangapandu

Dissertations and Theses (Open Access)

Metabolism of chronic lymphocytic leukemia (CLL), a disease characterized by the relentless accumulation of mature B cells has been little explored. Bone marrow stromal cells provide a survival benefit to CLL cells, in part through PI3K/AKT pathway. Compared with proliferative B-cell lines, metabolic fluxes of oxygen and lactate were low in quiescent malignant B lymphocytes from CLL patients. Glycolysis (extracellular acidification rate, ECAR) was consistently low in CLL samples, but oxygen consumption (OCR) varied considerably. Higher OCR was associated with poor prognostic factors such as ZAP 70 positivity, unmutated IgVH, high β2M levels, and higher Rai stage. Co-culture with the …

Nipt Results Indicative Of Maternal Neoplasms: Genetic Counselors' Preferences And Attitudes, Meagan E. Giles

Dissertations and Theses (Open Access)

Performing non-invasive prenatal testing (NIPT) on a pregnant woman with a chromosomally abnormal neoplasm may incidentally lead to the diagnosis of cancer due to the coexistence of circulating tumor and placental DNA. Published information regarding NIPT’s accuracy for neoplasm screening is limited, and guidance for patient management is currently lacking. This challenges clinicians’ ability to counsel patients regarding the implications of these results, which often is the responsibility of a genetic counselor. Over three hundred board-eligible/certified genetic counselors were surveyed regarding their awareness, preferences, and attitudes towards NIPT’s ability to indicate maternal neoplasms. Despite 95% of this cohort being aware …

The Role Of Amp-Activated Protein Kinase (Ampk) In Tumorigenesis, Fei Han

Dissertations and Theses (Open Access)

AMPK plays a central role in controlling cellular and whole body energy level. Increasing studies have also discovered the diverse function of AMPK in cancer, such as autophagy and mitochondria biogenesis. However, how AMPK promotes cancer progression is still not clear. Here, we show that AMPK is essential for EGF-induced Akt activation, Glut1 expression, and glucose uptake. AMPK is also required for various stresses induced Akt activation and promote cell survival, including hypoxia and glucose deprivation. In addition, we found glucose deprivation-induced VEGF expression and secretion is also depend on AMPK, which may contribute to angiogenesis of surrounding endothelial cell …

Preeclampsia: The Roles Of Acute Inflammation And Intrauterine Stress, Nicholas Parchim

Dissertations and Theses (Open Access)

Preeclampsia (PE) is a severe, acute disease of pregnancy affecting approximately 8% of pregnant women after week 20 of gestation. PE is characterized by hypertension and renal damage reflected by proteinuria and has significant morbidity to both mother and fetus. Maternal symptoms range from headaches, nausea, edema, to visual changes, but once maternal symptoms present, damage to the fetus has begun. Mothers who progress untreated through the disease can also experience a condition called eclampsia characterized by seizure, coma, and, ultimately, death. PE-affected newborns experience features similar to prematurity—abnormal lung and renal development, intrauterine growth retardation (IUGR), and, possibly, fetal …

The Novel Regulation Of Histone Modification In Cancer Development, Xian Zhang

Dissertations and Theses (Open Access)

Dynamic changes in histone acetylation by various physiological cues play important roles in gene transcription and cancer. However, the cellular signaling underlying this regulation is not well understood. Here, we show that, in a glucose dependent manner, E3 ubiquitin ligase NEDD4 ubiquitinates histone H3 on previously unstudied lysine (K) 23/36/37 residues, which specifically recruits histone acetyltransferase (HAT) GCN5 for subsequent H3 acetylation. Genome-wide analysis of chromatin immunoprecipitation followed by sequencing (ChIP-seq) data sets reveals that NEDD4 regulates glucose-induced H3K9 acetylation at transcription starting site (TSS) and enhancer regions. Integrative analysis of ChIP-seq and microarray data sets also reveals a consistent …

The Notch Target Hes4 Promotes Osteosarcoma Tumor Growth And Metastasis By Inhibiting Osteogenic Differentiation, And Has Potential As A Prognostic Biomarker For Newly Diagnosed Patients With High Grade Osteosarcoma., Madonna Mcmanus

Dissertations and Theses (Open Access)

Currently, there are no well-established prognostic biomarkers for osteosarcoma (OS) at the time of diagnosis. Although response to preoperative chemotherapy correlates with metastasis risk and overall survival, this information is obtained 3-4 months after the initial diagnosis. The major purpose of this study is to identify clinically relevant biomarkers that will allow for the stratification of patients into good or poor responders to chemotherapy at diagnosis. We also aim to understand the biology of these markers in OS pathogenesis. Because the development of OS is caused by genetic disruptions of osteogenic differentiation, we sought to identify pathways that are involved …

Gsk3Beta-Mediated Ezh2 Phosphorylation Suppresses Methylation Of H3k27 And Ezh2’S Oncogenic Functions, How-Wen Ko

Dissertations and Theses (Open Access)

During the process of tumorigenesis, inactivation of tumor suppressors is a critical step. Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and the enzymatic core subunit of polycomb repressive complex 2 (PRC2), promotes cell growth and migration through catalyzing trimethylation of histone H3 at Lys 27 (H3K27me3) and plays an important role in tumorigenesis. Its expression can be controlled by phosphorylation. However, the regulation of EZH2 activity by tumor suppressor kinase is not well understood. Glycogen synthase kinase 3 beta (GSK3b), a multifunctional serine/threonine kinase, is involved in many cellular processes. GSK3b also participates in neoplastic transformation, tumor development …

In Vivo Kinome Screen Reveals Non-Canonical Cdk-Driven Metabolic Adaptation In Brain Metastasis, Frank J. Lowery Iii

Dissertations and Theses (Open Access)

Brain metastasis, which frequently arises from breast cancer, lung cancer, melanoma, and colorectal cancer, remains a severely unmet medical need and its incidence continues to rise while treatment options remain palliative. To better understand the biology underlying its aggressive, incurable nature, I performed an unbiased in vivo kinome screen to identify potential driver kinases of experimental brain metastasis in a nude xenograft model using the human breast cancer cell line MDA-MB-231. Several of the kinase pools led to decreased brain metastasis-specific survival in nude mice, shortening survival time by up to 50% relative to controls. Targeted next-generation sequencing (NGS) was …

A Comparison Of Manual And Automated Grammatical Precoding On The Accuracy Of Automated Developmental Sentence Scoring, Sarah Elizabeth Janis

Theses and Dissertations

Developmental Sentence Scoring (DSS) is a standardized language sample analysis procedure that evaluates and scores a child's use of standard American-English grammatical rules within complete sentences. Automated DSS programs have the potential to increase the efficiency and reduce the amount of time required for DSS analysis. The present study examines the accuracy of one automated DSS software program, DSSA 2.0, compared to manual DSS scoring on previously collected language samples from 30 children between the ages of 2-5 and 7-11. Additionally, this study seeks to determine the source of error in the automated score by comparing DSSA 2.0 analysis given …

Inhaled Multiwalled Carbon Nanotubes Induce Systemic Inflammation And Endothelial Dysfunction Via Mmp-9 Induction, Mario Aragon

Biomedical Sciences ETDs

Assessing the mechanisms underlying adverse cardiovascular effects induced by inhaled toxins presents a substantial research challenge. We propose that blood carries an as yet unknown "inflammatory potential" consisting of modified proteins or other biomolecules and reaction byproducts that affects a pathological bioactivity which can be assessed using naïve endothelial cells and blood vessels. The approach involves applying serum from exposed animals to cultured primary endothelial cells or ex vivo isolated arteries. Mice were exposed to multi-walled carbon nanotubes (MWCNT; 0, 10 or 40 μg) or other pollutants via pharyngeal aspiration and serum was collected at 4 and 24 h post-exposure. …

Coordinating Community Healthcare Needs To Local Services In Paraiso, Dominican Republic Through Strategic Assessment Strategies, Michelle A. Cole, Christina B. Gunther, Majid Sadigh

Nursing Faculty Publications

Background: The availability of healthcare services is limited in Paraiso, Dominican Republic with the nearest full-service hospital located 34.1 km away. A local, underutilized clinic was unaware of the needs of this disadvantaged community.

Method: Researchers adapted a World Health Organization assessment survey with the goals of determining residents’ priority needs and an appraisal of the current clinic capabilities and gaps in services in order to provide the community with relevant healthcare. 106 families were randomly selected in seven separate geographic areas of Paraiso to participate in the self-report assessment. Researchers, along with a community volunteer, conducted interviews utilizing the …

A Hermeneutic Phenomenological Study Of The Lived Experience Of Adult Female Sexual Assault Survivors, Ann N. Hellman

Electronic Theses and Dissertations

Sexual assault is an international problem affecting hundreds of thousands of women each year. Significant psychological, physical, and financial consequences result from sexual assault. The prevalence of sexual assault suggests that nurses frequently encounter survivors yet minimal literature exists focusing on how nurses should adjust their care to meet the needs of this population.

The phenomenon of sexual assault has been widely studied from multiple perspectives and across disciplines. Likewise, studies of spiritual and religious beliefs and practices and their impact at the end-of-life and in disease, grief, and loss are extensive in nursing literature. However, a nominal number of …

Microwire Regenerative Peripheral Nerve Interfaces With Wireless Recording And Stimulation Capabilities, Ali Ajam

Theses and Dissertations

A scalable microwire peripheral nerve interface was developed, which interacted with regenerated peripheral nerves in microchannel scaffolds. Neural interface technologies are envisioned to facilitate direct connections between the nervous system and external technologies such as limb prosthetics or data acquisition systems for further processing. Presented here is an animal study using a handcrafted microwire regenerative peripheral nerve interface, a novel neural interface device for communicating with peripheral nerves. The neural interface studies using animal models are crucial in the evaluation of efficacy and safety of implantable medical devices before their use in clinical studies.16-electrode microwire microchannel scaffolds were developed for …

The Formal Approaches And Multicultural Considerations Of Assessing Aphasia For The Neurogenic Population From The Perspective Of A Monolingual Clinician, Lauren C. Carter

Theses and Dissertations

Aphasia is a neurogenic disorder, most commonly caused by stroke, which affects speaking, listening, reading, and/or writing skills. Persons with aphasia are typically left with communication limitations despite unaffected cognition. Many of the standardized assessments available for aphasia examination are not realistic instruments. Formal assessments are time consuming and rarely include multicultural or multilingual materials. The clinician must allow every opportunity for the PWA to demonstrate their communicative abilities during an aphasia assessment. This requires providing stimuli materials relevant to the PWA’s culture, assessing in the PWA’s primary language, and conducting the exam quickly to prevent fatigue. The ECLS-B is …

Individual Motivation And Threat Indicators Of Collaboration Readiness In Scientific Knowledge Producing Teams: A Scoping Review And Domain Analysis, Gaetano R. Lotrecchiano, Trudy Mallinson, Tommy Leblanc-Beaudoin, Lisa S. Schwartz, Danielle Lazar, Holly J. Falk-Krzesinski

Clinical Research and Leadership Faculty Publications

This paper identifies a gap in the team science literature that considers intrapersonal indicators of collaboration as motivations and threats to participating in collaborative knowledge producing teams (KPTs). Through a scoping review process, over 150 resources were consulted to organize 6 domains of motivation and threat to collaboration in KPTs: Resource Acquisition, Advancing Science, Building Relationships, Knowledge Transfer, Recognition and Reward, and Maintenance of Beliefs. Findings show how domains vary in their presentation of depth and diversity of motivation and threat indicators as well as their relationship with each other within and across domains. The findings of 51 indicators resulting …