Cell and Developmental Biology Commons^™

Exploring The Application Of Wastewater Monitoring To Determine The Prevalence And Diversity Of Influenza On The Campus Of West Virginia University, Lakyn Renee Sanders

Graduate Theses, Dissertations, and Problem Reports (ETD)

Influenza viruses (IV) affect populations globally, with the World Health Organization (WHO) estimating that IV are responsible for an estimated 3-5 million infections and 290,000 – 650,000 deaths annually^1–3. More specifically, the 2019-2020 IV season is associated with an estimated 38 million illnesses and 22,000 deaths in the United States alone⁴. IV are rapidly spread between individuals through direct contact with infected individuals, contaminated surfaces, or aerosolized virus particles². Traditional IV infection monitoring relies on clinical screening of patients presenting influenza-like symptoms, commonly through the use of multi-target panel tests such as the BioFire …

Gcn5l1-Mediated Lysine Acetylation Regulates Mitochondrial Dysfunction In The Aged Heart, Jackson Edmond Stewart

Graduate Theses, Dissertations, and Problem Reports (ETD)

For over a century, cardiovascular disease (CVD) has been and remains the leading cause of death globally. CVD risk and severity increase significantly with advanced age, and mitochondrial dysfunction has been implicated in the pathogenesis of aging. Furthermore, mitochondrial health is crucial for cardiac function, as one-third of total cardiomyocyte volume is occupied by mitochondria in order to meet the high energy demand of contractile and relaxational function. It is thus crucial that we understand the pathological mechanisms driving mitochondrial dysfunction in aging and how this contributes to age-associated cardiovascular disease. The current manuscript aims to fill this knowledge gap …

Studying The Mechanism For Ricin-Induced Growth Suppression, Daniel Judge

Graduate Theses, Dissertations, and Problem Reports (ETD)

This study focuses on ribosome-inactivating proteins (RIPs), a class of potent toxins that includes ricin, α-sarcin, and shiga toxin, which irreversibly damage large subunit rRNA. Although the catalytic activity of ricin toxin A chain (RTA) is well characterized, the precise mechanisms linking ribosome damage to altered cellular morphology remain poorly understood. In this study, we engineered a tetracycline-regulatable expression system to express RTA in Saccharomyces cerevisiae. We characterized the effects of RTA expression on yeast growth, viability, and reproductive potential. We demonstrated that our expression system produced rapid and robust RTA expression and ribosome depurination within less than one …

Dielectrophoretic Biomarkers For Cancer Detection And Cell Analysis: Integrating Microfluidics And Ai, Raphael Olumide Oladokun

Graduate Theses, Dissertations, and Problem Reports (ETD)

Pancreatic ductal adenocarcinoma (PDAC) carries a five-year survival rate of 13%, driven largely by late-stage diagnosis and the absence of sensitive noninvasive screening tools. Current diagnostic methods lack the sensitivity to detect disease-associated systemic changes at early and precancerous stages, representing a critical clinical gap. This dissertation addresses the central hypothesis that PDAC and its pathological subtypes induce measurable, disease-associated electrophysiological changes in circulating PBMCs that can serve as correlative liquid-biopsy biomarkers. To test this hypothesis, this work asks: can dielectrophoresis (DEP), impedance and zeta potential analysis with AI-assisted classification distinguish benign pancreatic conditions (non-malignant control), precancerous lesions (primarily IPMNs), …

Swarm Of One: Self-Organization In Multicellular Robots, Trevor Riley Smith

Graduate Theses, Dissertations, and Problem Reports (ETD)

Designing robots traditionally relies on centralized, top-down methods that constrain adaptability and resiliency, producing systems optimized for specific tasks. However, such systems often fail in complex environments, such as extraterrestrial, disaster, or natural settings, where designers cannot foresee every scenario a robot may encounter. Achieving autonomy in these contexts requires robots that are resilient and capable of adapting to the unknown. Multicellular organisms exhibit this adaptability through self-organization, where complex structures and behaviors emerge from local interactions among their cells. Such organisms can be viewed simultaneously as a single entity and a swarm of cooperating cells, i.e., a Swarm-of-One.

This …

Nuclear Aurka-Driven Early Dissemination Of Breast Cancer Uncovers Opposing Roles Of Hif-1a And Hif-1b In Metastasis, Abha Maskey

Graduate Theses, Dissertations, and Problem Reports (ETD)

ABSTRACT

Nuclear AURKA-driven early dissemination of breast cancer uncovers opposing roles of HIF-1A and HIF-1B in metastasis.

Abha Maskey

Metastatic progression is the primary cause of mortality in the majority of solid tumors, including breast cancer (BC). The triple-negative breast cancer (TNBC) is the most aggressive BC subtype with the highest recurrence rates within 1-3 years post-diagnosis, and worst overall survival outcomes. Early distant recurrence of cancer is enabled by early disseminated tumor cells (eDTCs), yet the mechanisms of early dissemination remain poorly defined. Hypoxia-inducible factor 1 (HIF1) is a transcription factor normally induced under hypoxia to enable cell survival. …

Xanthine Oxidoreductase, Uric Acid, And Iron Homeostasis: Discovering A Therapeutic Vulnerability In Breast Cancer, Matthew G. Chapa

Graduate Theses, Dissertations, and Problem Reports (ETD)

Breast cancer remains the most frequently diagnosed malignancy and the leading cause of cancer related deaths in women. This is primarily due to distant metastases, which highlight the necessity to understand factors that contribute to breast cancer progression. Emerging evidence associates decreased tumor xanthine oxidoreductase (XOR) expression with a poorer prognosis, increased recurrence, and a more aggressive phenotype. While healthy liver, intestines, kidneys, and breast tissue have robust XOR expression and activity, there is a tendency for this to be ablated in carcinogenesis. This dissertation investigates XOR's role in breast cancer and identifies its product, uric acid (UA), as possessing …

Neurobiological Variables Mediating The Relationship Between Breast Cancer And Sleep Disruption, Brittany Domenique Elliott

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neurobiological Variables Mediating the Relationship between

Breast Cancer and Sleep Disruption

Brittany D. Elliott, MS

Breast cancer is the most commonly diagnosed malignancy in women, with more than two million new cases diagnosed world-wide each year. Improvements in screening technology and diagnostics have increased survival rates, but cancer-associated sleep disruptions persist for the majority of breast cancer survivors well beyond the treatment period. In addition to reducing quality of life, reduced sleep quality is associated with greater incidences of affective dysfunction, reduced treatment efficiency, aggressive cancer progression, increased symptom severity, and increased mortality by all causes. Thus, identifying the variables …

Bridging The Gap Between Structural And Cellular Biology: Insight Into The Organization Of Glycolytic Enzymes In Cells, Heather Hansen

Graduate Theses, Dissertations, and Problem Reports (ETD)

Glycolytic enzymes are spatially organized in the cytoplasm, and are shown to localize with cellular structures such as the plasma membrane, F-actin, mitochondria, or associate independently within the cytosol. The assembly of these enzymes is hypothesized to regulate pathway flux to meet the energetic needs of the cell. However, it is unclear whether all of these assemblies have the same mechanism of formation or function in the cell. We investigated the role of glycolytic enzyme assemblies in cells, using the glycolytic “gatekeeper” enzyme phosphofructokinase-1 (PFK1). PFK1 is extensively regulated by multiple mechanisms, including over 20 allosteric ligands, post translational modifications, …

Molecular Insights Into The Impact Of Bone Marrow Stroma, Cb-6644 Inhibition Of The Ruvbl1/2 Complex, And Cebpβ On Regulating Drug Sensitivity In Multiple Myeloma, Sebastian Adam Dziadowicz

Graduate Theses, Dissertations, and Problem Reports (ETD)

Multiple myeloma (MM), is a hematological cancer originating in plasma cells. Currently multiple myeloma represents a significant clinical challenge due its incurable nature mainly due to inevitable drug resistance. MM is characterized by abnormal plasma cell proliferation within the bone marrow and production of abnormal immunoglobulin resulting in a plethora of physiological abnormalities. Although a rare malignancy, MM accounts for 1% of all cancers and currently has five-year survival rate of around 50%. Utilizing a combination of laboratory experiments and bioinformatics techniques, this dissertation examines multiple layers of MM physiology in the context of regulating drug resistance or sensitivity. First, …

A Rainy Day For Cancer: The Characterization And Utilization Of The Long Non-Coding Rna Lnc-Rainy In The Radiation Response Of Non-Small Cell Lung Cancer, Emily S. Rice

Graduate Theses, Dissertations, and Problem Reports (ETD)

Lung Cancer remains the leading cause of cancer-related deaths worldwide. While important improvements have been made to the treatment of non-small cell lung cancer (NSCLC), treatment resistance is a critical issue facing the majority of patients. Previously, our lab identified a group of long non-coding RNAs (lncRNAs) known as linc-SPRY3 RNAs, expressed on the Y-chromosome, that play a role in radiation sensitivity by decreasing tumor burden in vitro and in vivo after radiation. Through molecular cloning methods and further functional characterization, here we present evidence that the linc-SPRY3 RNAs were originally mischaracterized as individual linc-RNAs but are in fact parts …

Personalized Molecular Therapies For Advanced Non-Small Cell Lung Cancer: Overcoming Heterogeneity To Optimize Treatment Response And Clinical Outcomes, Zuan-Fu Lim

Graduate Theses, Dissertations, and Problem Reports (ETD)

Lung cancer remains one of the deadliest cancers. Novel, paradigm shifting treatments including immunotherapy and targeted therapies have recently been developed to cull the deadly effects of lung cancer, but many challenges remain. There remains a significant unmet need to accurately predict and optimally select for patients who will respond to immune checkpoint inhibitors (ICI) treatment. In Chapter 2 of this dissertation, we investigated a novel live single cell cytokine profiling lab-on-chip platform, IsoLight, using peripheral CD4+ and CD8+ T-cells for ICI biomarker development. A total of 55,175 single T-lymphocytes were analyzed in this proof-of-concept study. We found that an …

Aberrant Lipid Accumulation And Retinal Pigment Epithelium Dysfunction In Prcd-Deficient Mice, Sree Indrani Motipally

Graduate Theses, Dissertations, and Problem Reports (ETD)

Progressive Rod-Cone Degeneration (PRCD) is a peripheral membrane protein predominantly expressed in photoreceptor outer segment (OS) disc membranes with an unknown function. Several mutations in Prcd are implicated in Retinitis pigmentosa (RP) in humans. The most common “cysteine to tyrosine” (C2Y) mutation in Prcd leads to progressive retinal atrophy in multiple dog breeds and RP in humans. Canine models harboring the C2Y mutation in Prcd show disorganized OS structure with greatly attenuated photoreceptor OS renewal rates. Recent studies show defects in the photoreceptor nascent disc flattening in the absence of Prcd. However, it is unclear how OS discs eventually …

Immunomodulation In Osteosarcoma: From Therapy To Diagnostics, Ryan Austin Lacinski

Graduate Theses, Dissertations, and Problem Reports (ETD)

Osteosarcoma (OS) is a rare pediatric bone malignancy. Those who develop advanced disease, often in the form of metastasis to the lung, experience poor five-year survival rates near approximately 25%. Considering minimal-to-no therapeutic breakthroughs have occurred for treatment of this disease since the 1980s, efforts to develop new therapeutics are underway. The goal of this dissertation was to initiate the preclinical efforts necessary to reinvigorate the use of immunostimulatory cytokine therapy for the treatment of OS and other solid tumors. This effort would not only include the development of the immunotherapeutic known as IL12ns, but also the clinical diagnostic tools …

Cancer Promoting Neutrophil Extracellular Traps In The Pancreatic Ductal Adenocarcinoma Tumor Microenvironment, Abby Ivey

Graduate Theses, Dissertations, and Problem Reports (ETD)

Pancreatic adenocarcinoma (PDAC) is a very aggressive disease with an overall survival rate at 12%. This poor outcome at diagnosis is in part due to the lack of effective treatment options. The aggressive disease and unique tumor microenvironment generated during disease initiation and progression has contributed to the lack of effective therapeutic options. Chemotherapy options have not improved overall survival substantially, the effectiveness of radiation therapy remains controversial, and immunotherapies provide little to no benefit when added to current standards of care. Thus, there is a critical need for new therapeutics that can either target PDAC alone or be added …

Cell Signaling And Stress Response In The Yeast Saccharomyces Cerevisiae: A Study Of Snf1, Scott E. Arbet Ii

Graduate Theses, Dissertations, and Problem Reports (ETD)

Saccharomyces cerevisiae are yeast that are unicellular eukaryotic organisms that are well studied as a model organism for understanding fundamental cellular processes. The ability of yeast to sense nutrient availability is crucial for their survival, growth, and reproduction. Yeast cells use various mechanisms to sense and respond to nutrient availability, including transporter-mediated uptake, receptor-mediated signaling, and sensing of metabolites. The subcellular localization of nutrient-sensing components is crucial for yeast function in nutrient sensing and signaling. Protein complexes, such as the AMP-activated protein kinase (AMPK) pathway, in nutrient sensing and response, as well as the downstream effects of these pathways …

The Investigation Of Novel Bovine Oocyte-Specific Long Non-Coding Rnas And Their Roles In Oocyte Maturation And Early Embryonic Development, Jaelyn Zoe Current

Graduate Theses, Dissertations, and Problem Reports (ETD)

Early embryonic loss is a significant factor in livestock species' infertility, resulting in an economic deficit. In cattle, the in vivo fertilization rate is ~90%, with an average calving rate of about 55%, indicating an embryonic-fetal mortality rate of roughly 35%. Further, 70-80% of total embryonic loss in cattle occurs during the first three weeks after insemination, particularly between days 7-16. Growing evidence indicates that the oocyte plays an active role in regulating critical aspects of the reproductive process required for successful fertilization, embryo development, and pregnancy. However, defining oocyte quality remains enigmatic. Recently, many have abandoned the notion that …

Elucidation Of The Role Of Agouti-Signaling Protein Throughout Folliculogenesis And Early Embryonic Development In Cattle, Heather L. Chaney

Graduate Theses, Dissertations, and Problem Reports (ETD)

The oocyte expresses certain genes during folliculogenesis to regulate the acquisition of oocyte competence. Oocyte competence, which refers to the presence of imperative molecular factors in the oocyte that are critical for high oocyte quality, is directly related to the ability of the oocyte to result in a successful pregnancy following fertilization. Over the past few decades, the development and optimization of assisted reproductive technologies, particularly in vitrofertilization, have enabled the beef and dairy industries to advance cattle genetics and productivity. However, only approximately 40% of bovine embryos will develop to the blastocyst stage in vitro. In addition, bovine embryos …

The Role Of Nedd9 In Her2-Driven Breast Cancer., Marc Louis Purazo

Graduate Theses, Dissertations, and Problem Reports (ETD)

Tumor initiation is often driven by unrestricted proliferation. One such driver of proliferation is Human epidermal growth factor receptor 2 (HER2). HER2 is a receptor tyrosine kinase that is part of the epidermal growth factor receptor family (EFGR) that is commonly overexpressed in breast cancer. HER2 positive (+) breast cancers often respond to anti- HER2 therapy, yet many patients eventually develop resistance. Multiple mechanisms contribute to resistance, including activation of HSP90, PI3K/Akt or Src that rely on adaptor molecules (GRB2, p130cas, NEDD9). Neural precursor cell expressed, developmentally downregulated protein 9 (NEDD9) is an adaptor protein that promotes integrin signaling. We …

Utilizing Pharmacology To Target Transcription Factors Involved With Cancer Onset And Development, Tristan D. Sanders

Mountaineer Undergraduate Research Review

Transcription factors (TFs) are a vital part of every living organism on earth, as they allow for the correct genes to be expressed while much of the genome is never used. They can fall victim to mutations or manipulations that lead to the deregulation of many genes within a cell. If specific genes are over/under-expressed, a cell may become cancerous and begin replicating into a tumor. It has been demonstrated that common TFs associated with cancer can be targeted using small molecule drugs, and a popular target of these drugs is the DNA binding site on the TF along with …

Genetic Underpinnings Of Novel Trait Development In A Euwallacea-Fusarium Mutualism, Elaina J. Spahr

Graduate Theses, Dissertations, and Problem Reports (ETD)

Evolutionary Developmental Biology seeks to answer fundamental questions about the mechanisms underlying the evolution and innovation towards increasing structural complexity within the body plan. The ambrosia symbiosis, a polyphyletic group of xylem-feeding beetles, provides a wealth of diversity in novel pouch-like structures called mycangia. This diversity could serve as a rich model for understanding how mutualisms may prompt structural innovation and diversification in a host organism. The ambrosia symbiosis has become a fast-growing research subject in entomology and forest pathology but has yet to experience the same attention under the lens of evolutionary developmental genetics.

Development of mycangia was examined …

Getting To The Root Cause: The Genetic Underpinnings Of Root System Architecture And Rhizodeposition In Sorghum, Farren Smith

Graduate Theses, Dissertations, and Problem Reports (ETD)

Plants are some of the most diverse organisms on earth, consisting of more than 350,000 different species. To understand the underlying processes that contributed to plant diversification, it is fundamental to identify the genetic and genomic components that facilitated various adaptations over evolutionary history. Most studies to date have focused on the underlying controls of above-ground traits such as grain and vegetation; however, little is known about the “hidden half” of plants. Root systems comprise half of the total plant structure and provide vital functions such as anchorage, resource acquisition, and storage of energy reserves. The execution of these key …

Tumor-Targeted Ph-Sensitive Manganese Oxide Nanoparticle For Enhanced Detection Of Breast Cancer Using Mri, Celia Martinez De La Torre

Graduate Theses, Dissertations, and Problem Reports (ETD)

In the United States, approximately 287,850 new cases of invasive breast cancer will be diagnosed, and over 43,000 women will die because of it in 2022. Currently, mammography is the gold standard for breast cancer surveillance. Although this detection technique is relatively cheap and fast, it misses about 1 in 5 breast cancers in younger women with dense breast tissue, causing a delay in treatment. Compared to mammography, magnetic resonance imaging (MRI) has superior soft-tissue contrast that elucidates structural differences within soft tissue to detect more breast cancers. However, MRI still misses

NEMO particles were produced by synthesizing manganese oxide …

Characterization Of Two Krab-Containing Zinc Finger Transcription Factors In Bovine Preimplantation Embryonic Development, Mingxiang Zhang

Graduate Theses, Dissertations, and Problem Reports (ETD)

Oocyte developmental competence or oocyte intrinsic quality describes the capability of oocytes to resume meiosis, cleave and develop to blastocyst stage after fertilization, implant and develop to term in a good health. A growing number of evidences indicate that the majority of embryonic mortality occurs during early embryonic development in different species, including human, horse and cattle primarily due to poor oocyte quality. Maternal effect genes are key aspects of oocyte quality, which are transcribed during the process of oogenesis and folliculogenesis. The maternal factors are accumulated in oocytes, orchestrating various early developmental events including fertilization, epigenetic reprogramming and zygotic …

An Investigation Into The Mechanism Of Proteasome Dysfunction In Neurodegenerative Disease And The Biological Impact Of Proteasome Hyperactivation In C. Elegans, Raymond T. Anderson

Graduate Theses, Dissertations, and Problem Reports (ETD)

Aging is an inevitable process that occurs as humans grow older. It is characterized by the chronological accumulation of cellular damage over time leading to functional decline as an organism grows older. Several processes are thought to contribute to the aging phenomenon, but one of the most prolific of these is the disruption of protein homeostasis (proteostasis). The collapse of proteostasis can lead to accelerated aging and the development of age-related diseases including devastating neurodegenerative diseases (NDs) like Alzheimer and Parkinson disease. Virtually all NDs are characterized by the buildup of proteins in and around neurons resulting in neuronal death …

Ero1Α Promotes Tumorigenesis In Egfr Driven Nsclc, Brennan D. Johnson

Graduate Theses, Dissertations, and Problem Reports (ETD)

Non-Small Cell Lung Cancer (NSCLC) is a pulmonary malignancy most commonly associated with smoking, or exposure to asbestos or Radon. Approximately, 1.6 Million deaths occur each year due to lung cancer. Lung Cancer is categorized by two main types, Small Cell Lung Cancer (SCLC) and NSCLC. NSCLC accounts for approximately 85% of all lung cancer cases and is subdivided into three sub-categories: Adenocarcinoma, the most common and leading cause of death in the United States; Squamous Cell Carcinoma (SCC), and Large Cell Carcinoma. Though NSCLC treatment regimens have shown increasing clinical benefit over the last two decades with targeted therapies. …

Actin Cytoskeletal Regulation And Matrix Metalloproteinase Targeting In Head And Neck Squamous Cell Carcinoma (Hnscc) Progression, Jessica Lea Allen

Graduate Theses, Dissertations, and Problem Reports (ETD)

Head and neck squamous cell carcinoma (HNSCC) is a cancer originating from the epithelial lining of the oral cavity, larynx, and pharynx. HNSCC is associated with extensive locoregional invasion and tissue destruction. Invasive processes underlying HNSCC contribute to poor prognosis and decreased quality of life. Amplification of chromosome 11q13 is the most common DNA aberration in human papilloma virus negative (HPV^-) HNSCC. This region includes various genes known to drive tumor progression. CORO1B (coronin 1B) flanks the core 11q13 region and is amplified in 7-14% of HNSCC. Coronin 1B is essential for mesenchymal cell motility by promoting turnover …

From Inner Segment To Outer Segment: Palmitoylation Of Photoreceptor Na+, K+-Atpase And The Importance Of Prcd In Photoreceptor Outer Segment Morphogenesis, Emily R. Sechrest

Graduate Theses, Dissertations, and Problem Reports (ETD)

Photoreceptors are specialized neuroepithelial cells which are optimized for efficient capture of light and initiation of visual transduction. These cells have several compartments which are very important for proper visual function and segregation of cellular processes, including the outer segment (OS), inner segment (IS), nucleus, and synapse. The IS houses all of the cellular organelles and biosynthetic molecular machinery the cell requires and is the site of protein synthesis. The light-sensing OS is a highly modified, primary cilium, which contains many stacks of double membranous discs which house proteins required for formation and maintenance of OS structure, as well as …

Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls

Graduate Theses, Dissertations, and Problem Reports (ETD)

This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …

Using Zebrafish To Elucidate The Expression And Gene Regulatory Network Of The Genomic Screen Homeobox Transcription Factors And Bring Innovative Science Learning Experiences To West Virginia, Rebecca Ann Coltogirone

Graduate Theses, Dissertations, and Problem Reports (ETD)

Central nervous system (CNS) development requires a code of regionally expressed transcription factors that impart initial neuronal cell identity, connectivity, and function. The absence of a transcription factor code would eliminate the neurodevelopmental logic producing diverse cell types in the CNS. Furthermore, early disruptions in transcription factor expression can affect later connectivity and function of neuronal circuits mediating sensory processing, defects in which are often observed as comorbid with various neurodevelopmental disorders (NDDs). Characterizing transcription factor expression and function is therefore an essential step in discerning the molecular mechanisms underlying human NDDs. genomic screen homeobox 1 and 2 (gsx1 …