Life Sciences Commons^™

An Investigation Of Epigenetic Mechanisms Driving The Biology Of Head And Neck Squamous Cell Carcinoma, Scot Carson Callahan

Dissertations and Theses (Open Access)

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and is associated with significant morbidity and mortality. To date, the majority of work in the field has focused on genomic alterations such as mutations and copy number alterations. However, the clinical success of targeted therapies that exploit known genomic alterations, such as EGFR mutations, has remained mixed. Over the past decade, the importance of epigenetic regulators has come to the forefront, with the realization that many of these genes are mutated in cancer. Despite this realization, the role of epigenetics in regulating tumorigenesis, progression and …

Modulation Of Kras Structure And Dynamics By Kras Ubiquitination And Membrane Depolarization, Vinay Nair

Dissertations and Theses (Open Access)

KRAS, a 21 kDa small GTPase protein, functions as a molecular switch playing a key role in regulating cell proliferation. Dysregulation of KRAS signaling by oncogenic mutations leads to uncontrolled cell proliferation, a hallmark of cancer cells. Attempts to therapeutically target oncogenic KRAS have led to limited success resulting in a need to identify new mechanisms to targeting KRAS. The interaction of KRAS with its regulators, effectors, and the membrane present one such avenue. In this study, we investigated how post-translational covalent and environmental modifications could modulate these interactions of KRAS. Using computational molecular dynamics simulations, nuclear magnetic resonance spectroscopy …

Investigation Of Genomic Instability Induced By G-Quadruplexes In The Absence Of Functional To Poisomerase 1 In Yeast, Alexandra Berroyer

Dissertations and Theses (Open Access)

Topoisomerase 1 (Top1) is an enzyme that removes transcriptionally generated negative supercoils by binding and nicking DNA. Since transcription of guanine-rich DNA leads to the formation of G-quadruplex (G4) structures, Top1’s function likely suppresses G4-formation. In support of this, Top1 significantly reduces co-transcriptional G4 DNA-associated genomic instability at a model G4-motif in Saccharomyces cerevisiae. However, whether Top1 suppresses G4-formation on a genome-wide scale in yeast remains unexplored. Therefore, I aimed to uncover if deletion of Top1 enhances genome-wide G4-formation in S. cerevisiae. As an approach to quantify global G4-formation, I expressed the G4-specific antibody BG4 from a yeast …

Integration Of Biomedical Imaging And Translational Approaches For Management Of Head And Neck Cancer, Abdallah Mohamed, Abdallah Mohamed

Dissertations and Theses (Open Access)

The aim of the clinical component of this work was to determine whether the currently available clinical imaging tools can be integrated with radiotherapy (RT) platforms for monitoring and adaptation of radiation dose, prediction of tumor response and disease outcomes, and characterization of patterns of failure and normal tissue toxicity in head and neck cancer (HNC) patients with potentially curable tumors. In Aim 1, we showed that the currently available clinical imaging modalities can be successfully used to adapt RT dose based-on dynamic tumor response, predict oncologic disease outcomes, characterize RT-induced toxicity, and identify the patterns of disease failure. We …

Innate Lymphoid Cell Characterization And Ilc2s In Neuroinflammation In Aging And Sex Differences, Alexis Mobley, Alexis S. Mobley

Dissertations and Theses (Open Access)

Aging affects immunologic responses by a global immune system suppression, including dysregulation of cytokine mediators, leading to increased inflammation throughout all systems, termed inflammaging. However, understanding healthy aging mechanisms can bypass this effect. Inflammaging also leads to poor outcomes during brain injury, making immune-targeting therapeutics tantamount to overall brain health and longevity. Moreover, sex affects disease etiology and severity through hormonal and chromosomal sex, as the X chromosome contains most immunology-based genes. Androgens have a generally suppressive effect on the immune system. Additionally, when immune responses are mounted, males are better at CD4+ T cell type (Th1) responses, while females …

Experiences Of Racial And Ethnic Minority Patients With Genetic Counseling, Emile Moura Coelho Da Silva

Dissertations and Theses (Open Access)

Racial and ethnic minority patients in the United States undoubtedly suffer from inequalities in healthcare. While some studies have explored these inequalities in the field of genetic counseling specifically, research relating to genetic counseling outcomes in diverse patient populations is still limited. With the number of non-Hispanic White individuals in the United States projected to decrease by 20 million by 2060, it becomes imperative to better understand the experiences of racial and ethnic minority patients to meet their needs. Therefore, this study aimed to further describe the experiences of racial and ethnic minority patients who received genetic counseling services. In …

Impact Of Brain State On Visual And Prefrontal Population Coding In Behaving Animals, Russell Milton

Dissertations and Theses (Open Access)

Patterns of neural activity in the brain constantly shift between different processing states. Earlier studies have established that the ongoing, spontaneous activity has major repercussions regarding how the brain processes incoming sensory stimuli. However, the interaction between behavioral activity and brain states throughout the cortical hierarchy of primates has not been understood. In particular, technical considerations have greatly limited the range of physical activities in which primate neuronal activity can be recorded. We have implemented two separate strategies to overcome these limitations. First, we have advanced wireless electrophysiological methodologies that enable recording high-yield neuronal data from animals as they freely …

Development And Characterization Of B7-H3-Targeted Radioimmunotherapies For The Treatment Of Solid Tumors, Sarah Glazer

Dissertations and Theses (Open Access)

Radioimmunotherapy involves the selective targeting of therapeutic radionuclides to cancer-associated cell surface antigens using monoclonal antibodies. Radioimmunotherapy has been successful in treating hematologic cancers, such as non-Hodgkin’s Lymphoma. However, treatment of solid tumors by radioimmunotherapy remains a challenge, driven in part by a lack of high affinity antibodies against highly tumor-selective surface antigens. Herein, we characterize novel anti-B7-H3 immuno-conjugates for PET imaging and RIT of solid tumors in preclinical models.

Human B7-H3 (CD276) protein is highly expressed on solid tumor cell surfaces and endovascular surfaces in a wide variety of cancers (colon, breast, pancreatic, prostate, head and neck, glioblastoma, ovarian, …

Tissue-Specific Matrix Control Of Cell Cohesion And Migration Signaling Complexes, Tristen Tellman

Dissertations and Theses (Open Access)

The extracellular matrix (ECM) is a complex, interconnected network of three major constituents: collagens, glycoproteins, and proteoglycans, along with their enzyme modifiers. Within this network and beyond the structural role, each ECM molecule contributes a context-specific signal that influences cellular fate and behavior. Among these behaviors, cellular migration provides an essential function in developing tissues, wound healing, and cancer cell metastasis. Using two glandular organs, the normal salivary gland and the cancerous prostate, this dissertation describes the tissue-specific composition of two ECM signaling complexes (type I hemidesmosomes and the perlecan-semaphorin 3A-plexin A1-neuropilin-1 (PSPN) complex) and translates this knowledge into viable …

Invisible Disabilities, Academic Capital And Competitiveness Of Genetic Counseling Applicants, Natalie E. Stoner, Meagan Choates, Carla Mcgruder, Debra Murray, Theresa Wittman, Sara Wofford, Claire N. Singletary

Dissertations and Theses (Open Access)

The field of genetic counseling has historically lacked diversity. Recent research has begun to explore how visible diversity may present barriers to a genetic counseling applicant becoming competitive, but has not yet characterized potential barriers with invisible diversities, such as being a first-generation college student, or a part of the LBGTQ+ community. Therefore, this study aimed to address this gap among those with invisible diversities, as well as explore their academic capital (AC), a theoretical framework used to identify factors that make students more likely to succeed in post-secondary work including supportive networks, trustworthy information, family uplift, college knowledge, overcoming …

The Effect Of Cognitive Status And Residency On Oral Health In Patients With Dementia, Nicole Stephens

Dissertations and Theses (Open Access)

Poor oral health is a predictor of cognitive decline in elderly populations and has been shown to precede dementia. As cognitive decline progresses, patients are likely to move from the community into nursing facilities. We hypothesize that severity of dementia and residency type will impact the oral health of patients with dementia. Fifty-two participants of two dementia levels were recruited from the UTHealth Neurocognitive Disorders Center and two Houston-area nursing homes. A standardized oral health assessment, plaque index, and oral bacteria analysis determined participants’ oral health status. Further, data was collected on participants’ medical history, oral hygiene habits, dietary habits, …

Computational Approaches To Understand Chemoresistance & Tumor Evolution Using Longitudinal Clinical Data And Lineage Tracing, Sahil Seth

Dissertations and Theses (Open Access)

Tumors are highly heterogeneous and dynamic, continually adapting and evolving in response to their microenvironment as well as external perturbations. Multi-region (spatial) and single cell sequencing has enabled us to anatomize the heterogeneity further and provide evidence of its association with chemo and drug resistance. To investigate this further we took two different approaches to understand the chemo-resistance, and functional heterogeneity in Triple negative breast cancer (TNBC) and Pancreatic ductal carcinoma in situ (PDAC) from an evolutionary perspective.

The first approach was to leverage tumor profiling from an ongoing randomized clinical trial in triple-negative breast cancer (ARTEMIS) to assess mechanisms …

The Tca Cycle As A Nexus Of Metabolic Vulnerabilities In Cancer, Sunada Khadka

Dissertations and Theses (Open Access)

Uncontrolled proliferation of cancer cells necessitates rewiring of metabolic pathways to meet biosynthetic and bioenergetic demands of proliferation and fortify redox homeostasis. An increasing body of literature suggests that mitochondrial metabolism (tricarboxylic acid cycle (TCA) and oxidative phosphorylation) is imperative for cancer cell growth and proliferation. The scope of the works presented in this dissertation is to explore the importance of mitochondrial metabolism, and primarily the TCA cycle—the anabolic factory of cancer cells and leverage it as a targetable vulnerability in cancer. Cancer cells consume anabolic nutrients that are used to generate biosynthetic precursors in the TCA cycle. Continuous efflux …

Plant Homeodomain Finger Protein 20 (Phf20) And Its Homolog Phf20 Like 1 (Phf20l1) Define Two Distinct Non-Specific Lethal (Nsl) Complexes, Hieu Van, Hieu T. Van

Dissertations and Theses (Open Access)

Plant Homeodomain Finger Protein 20 (PHF20) and its homolog PHF20 Like 1 (PHF20L1) are known subunits of the Non-Specific Lethal (NSL) complex, which acetylates lysine residues on histone H4 and regulates gene expression. The current model assumes that PHF20 and PHF20L1 are present together in the NSL complex, although it has never been tested. Performing extensive biochemical analysis, we observed that PHF20 and PHF20L1 were exclusively and independently associated with the NSL complex. Our protein domain analysis showed that the C-termini of PHF20 and PHF20L1 are crucial for their interactions with the respective complexes. Furthermore, enrichment sites of PHF20 and …

Optimization Of Modular, Long-Range, Ultra-Fast Optical Tweezers With Fluorescence Capabilities For Single-Molecule And Single-Cell Based Biophysical Measurements, Subash C. Godar

All Dissertations

An Optical tweezer is a tightly focused laser beam that applies and senses precise and localized optical force to a dielectric microsphere and offers a unique and effective tool for manipulating the single cell or cell components, including nucleotides and dynein motor proteins. Here, I used highly stabilized optomechanical components and ultra-sensitive detection modules to significantly improve the measurement capabilities over a wide range of temporal and spatial scales. I combined the optical tweezer-based force spectroscopy technique with fluorescence microscopy to develop an integrated high-resolution force-fluorescence system capable of measuring displacements at sub-nanometer, forces at sub-piconewton over a temporal range …

Effects Of Continuous In Situ Low-Dose Ionizing Radiation On Microorganisms, Molly E. Wintenberg

All Dissertations

Precise detection and monitoring of nuclear fuel cycle, enrichment, and weapon development activities are critical for supporting warfighter preparation in chemical, biological, radiological, nuclear, and explosives (CBRNE) operations, clandestine activities, and nuclear compliance. A biological sensing system could serve as an alternative to traditional detection methods by using organic material naturally present in the environment to discreetly detect residual trace nuclear material. Microorganisms provide an optimal platform for an alternative sensing system; however, their response to low levels of ionizing radiation is poorly characterized. Combining the power of next-generation sequencing and transcriptomic analysis, this dissertation takes an approach to obtain …

At-Home Yogurt Making To Investigate Microbiology Concepts: A Remote Biology Laboratory, Tatiana Kuzmenko, Jacqueline Raetz-Vigon, Demian A. Willette

Biology Faculty Works

The global COVID-19 pandemic has forced many educators to move their courses to the online environment with little time to adjust. It especially affected undergraduate biology laboratory courses that rely on on-campus facilities to provide students with meaningful laboratory-type experiences. Here we describe a multisession, at-home, and hands-on laboratory activity that utilizes yogurt culturing to explore microbiology concepts. We also summarize the findings of 219 undergraduate students who successfully performed this lab remotely. In small virtual groups, students learned how to make yogurt at home, formulate a testable hypothesis, run an experiment on conditions necessary for yogurt fermentation, analyze experimental …

Preparation Of Proteins And Peptides From Heat-Stabilized Defatted Rice Bran Via Solid State Fermentation And Investigating For Skin Health, Ali A. Bisly

Graduate Theses and Dissertations

Heat-stabilized defatted rice bran (HDRB) is an abundant and inexpensive agro-industrial by-product of rice milling and rice oil extraction process. Furthermore, HDRB is a potential source of proteins. However, the direct protein extraction has low yield of protein due to the impact of heat stabilization and oil extraction process which made the HDRB proteins bound and interact with other components. This research is based on using solid-state fermentation (SSF), which is a natural and cost-effective approach to facilitate protein extraction from HDRB using Bacillus subtilis (natto) Takahashi as a microorganism.

Response surface methodology (RSM) analysis was used with Box-Behnken design …

Genetic Control Of Prickles And Plant Height In Blackberry, Carmen Johns

Graduate Theses and Dissertations

The fresh-market blackberry (Rubus L. subgenus Rubus Watson) industry has been expanding for the past two decades. Blackberry market growth can be attributed to many factors including expanded production regions, improved production systems, and release of superior cultivars. Blackberry breeding is a time- and labor-intensive process which would benefit from implementation of molecular markers for highly heritable, important traits. Next generation sequencing, a high-quality reference genome, and software capable of analyzing this complex genome were applied in a genome-wide association study (GWAS) to reveal maker-trait associations related to prickles and plant height variation in fresh-market blackberry. In 2020 and 2021, …

Study Of Adaptive Radiation Effects On Sprint Performance In Anolis Ecomorphs, Alexander J. Bergeson

Honors Thesis

Anolis lizards have become model organisms for the study of adaptive radiation and convergent evolution due to repeated patterns of specialization that allow them to live in different environmental niches within the habitats they occur. As part of a suite of adaptations for living in specific habitats, many species have repeatedly evolved specific changes in anatomy and physiology that make them better able to perform and survive in their surroundings. These specialized forms are referred to as “ecomorphs” based on their preferred habitats and have been well documented among Caribbean anoles. Mainland species, on the other hand, are less studied. …

Characterizing Gray Snapper (Lutjanus Griseus) Life History In The Northcentral Gulf Of Mexico: Age And Growth, Mortality, And Reproduction, Edward Kim

Graduate Theses and Dissertations (2019 - present)

Gray Snapper (Lutjanus griseus) constitute a significant recreational fishery and minor commercial fishery throughout the Gulf of Mexico, and review of the recent assessment determined that the stock is overfished and has been undergoing overfishing. The absence of regional baseline data in the northcentral Gulf of Mexico, combined with projections of range expansion and subsequent population growth due to climatic warming, highlight the need for the present investigation into the age and growth, mortality, and reproduction of this species in Alabama and Mississippi. Sex-specific growth curves constructed using the von Bertalanffy growth function demonstrated a significantly greater mean asymptotic length …

Site Fidelity Of Bottlenose Dolphins (Tursiops Truncatus) Using Elemental Analyses And Photo-Identification, Lauren R. Clance

Graduate Theses and Dissertations (2019 - present)

The objective of this study was to determine if bottlenose dolphins (Tursiops truncatus) in Alabama waters acquire location-specific elemental signatures indicative of site fidelity. I measured trace metal concentrations (Chapter II) and stable isotope ratios (Chapter III) in skin from free-ranging dolphins remotely biopsied in Mobile Bay, the northern Gulf of Mexico (Gulf) and eastern Mississippi Sound (EMSS). Elemental findings were corroborated with photo-identification data. I found that dolphins acquired some location-specific elements indicative of site fidelity, with the greatest differences at geographic extremes, particularly relative to salinity. For trace metals, highest concentrations were found in winter, consistent with higher …

Coastal Sediment Response To The Diel Oxygen Cycle, Kara Gadeken

Graduate Theses and Dissertations (2019 - present)

Shallow coastal sediments are sites of intense respiration and organic matter breakdown. Macroinfauna bioturbate and bioirrigate sediments which supplies microbes with oxygen and newly deposited organic material from surface sediments, facilitating microbial remineralization of organic matter. These processes depend heavily on the concentration of dissolved oxygen in overlying water. Shallow water oxygen patterns often follow a diel cycle as dissolved oxygen decreases at night due to respiration and then increases during the day with photosynthesis, creating recurring suboxic conditions that are potentially stressful to organisms. Sediment oxygen flux is known to depend on ambient dissolved oxygen concentration, but behavioral responses …

Alfred Russel Wallace Notes 21: Wallace & The Doorway To The Universe, Charles H. Smith

Faculty/Staff Personal Papers

An important yet largely unrecognized theme in the thought of Alfred Russel Wallace (1823−1913) was his insistence that all dependably-reported phenomena, even those of aberrant nature, were worthy of a respectful kind of attention: that is, a kind which did not automatically banish difficult subjects to the realm of myth or superstition. In this work, Wallace’s philosophy in this direction is documented, and linked to the world of post-Age-of-Enlightenment revisionism.

Investigation Of The Binding Domain Interfaces Of The C-Terminus Of The Albino3 Insertase And The 43kda Chloroplast Signal Recognition Particle Subunit Via Single Molecule Förster Resonance Energy Transfer, Amanda Tomanek

Chemistry & Biochemistry Undergraduate Honors Theses

Fluorescent labeling is a technique used for visualizing functional groups contained in biomolecules by fluorescence imaging. This technique was used in this project to analyze post-translational targeting of light-harvesting chlorophyll-binding proteins (LHCP), which are the core complexes that harvest sunlight to drive photosynthetic electron transfer. This protein is synthesized in the cytosol and post-translationally targeted to the stroma of chloroplasts. CpSRP43 is a signal recognition particle (SRP) subunit unique to chloroplasts, which has been shown to interact with the stroma-soluble C-terminus of the thylakoid-bound Albino3 insertase (Alb3-Cterm). In the chloroplast stroma, targeting to thylakoids is performed via the cpSRP pathway …

Synthesis, Structural Characterization, And In Vitro Biological Assessment Of Trans- Platinum (Ii) Thionate Complexes As Potent Anticancer Agents, Mia Alshami

Chemistry & Biochemistry Undergraduate Honors Theses

The content of this thesis has been originally reported in our published paper, “trans-Platinum (II) Thionate Complexes: Synthesis, Structural Characterization, and in vitro Biological Assessment as Potent Anticancer Agents” ChemPlusChem 2019 84, 1525-1535, DOI: 10.1002/cplu.201900394, in which I served as coauthor. Cancer caused 9.6 million deaths in 2018 worldwide, with 18.1 million new diagnoses during that same year.The most widely used metal in anticancer drugs is platinum (Pt), and these drugs are used to treat almost 50% of cancer patients. To optimize drug effectiveness, trans-configured Pt(II) complexes have been introduced as a strategy to potentially overcome the …

Epidemiology And Impacts Of A Leaf Spot Disease In Veratrum Viride (Melanthiaceae), Leeah R. Sutton, Foster Levy

Undergraduate Honors Theses

Fungal phytopathogens can cause disease epidemics in crops, weeds, and
populations of native plants. To investigate the impact of a foliar phytopathogen on the native herbaceous species, Veratrum viride, a demographic and disease assessment was carried out on two high elevation grassy bald populations on Roan Mountain, Tennessee. A leaf spot disease impacted all plants in both populations, causing widespread premature senescence of leaves and stems. Disease severity increased over the course of the growing season. Based on host disease symptoms and fungal conidia morphology, Pseudocercosporella sublineolata was shown to be the causal pathogen. A study of herbarium specimens …

The Impacts Of Holocene Climate And Pre-Columbian Humans On Neotropical Andean Forests, Rachel Kathleen Sales

Theses and Dissertations

Humid montane forests in the tropical Andes form hotspots for biodiversity, endemism, and conservation. Threats to the forests from deforestation are amplified by ongoing climate change, which could further reduce available habitat area by about 57 – 80%. These forests are known to have withstood considerable climate change in the past, and an emerging view suggests that they have also been shaped by a long interaction with people. Although climate-driven species range shifts are broadly known, questions remain about how past climate change has affected the species composition of these forests. The interaction of people with forests on the eastern …

The Form And Function Of Cranial Spines In Fishes, Louis Michael Penrod

Theses and Dissertations

Despite the prevalence of fishes that express cranial spines, quantitative investigations into the function of these spines are rare. Function is often assumed with little or no evidence. Commonly, spine-like structures are considered to be used for defense despite spines potentially being used for other purposes. Here, I took a high-level approach to investigate the morphology and potential functions of cranial spines in over 2000 fishes. Identifying the function of cranial spines in fishes not only informs us as to how these fishes interact with conspecifics, with other species, and with their environment, but also may provide advances in human …

Evaluating Methods To Determine The Maximum Oxygen Consumption By The Gulf Killifish, Fundulus Grandis, Sylvia Mullen

Senior Honors Theses

Metabolic rate is an essential feature of animal physiology and ecology. The rate of aerobic metabolism, as determined by oxygen consumption rate (MO2), is influenced by a variety of factors, including body size, temperature, and activity levels. Maximum aerobic metabolic rate (MMR) reflects the physiological capacity of an animal for oxygen extraction and utilization. As such, MMR is argued to be an important feature of an animal’s life history. For fish, MMR is frequently estimated as the peak MO2 immediately following an exhaustive chase, although several studies indicate that this value may underestimate MMR. Rather, MMR may be attained during …