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The Role Of Tumor Microenvironment In Glioblastoma Multiforme(Gbm) Therapeutic Resistance, Kwesi E. Taylor

Master's Theses or Doctor of Nursing Practice

Despite significant advances in cancer research and treatment, Glioblastoma multiforme (GBM) remains one of the most difficult cancers to treat effectively, with minimal improvement in long-term survival rates over the past few decades. This is largely attributed to tumor heterogeneity and the ability of tumor cells to develop adaptive resistance mechanisms supported by the tumor microenvironment (TME). Although the TME is recognized as a key contributor to tumor progression and therapeutic resistance, the underlying molecular pathways and regulatory genes remain incompletely understood. This study investigated the role of the tumor microenvironment in GBM therapeutic resistance using a bioinformatics approach. Single-cell …

Bayesian Multivariate Modelling Of Lone Star (Amblyomma Americanum) Tick Life Stage Abundance And Temporal Trends To Inform Public Health Risk In Virginia, Thabo Lephoto, Henry Mwambi, Oliver Bodhlyera, Holly Gaff

Biological Sciences Faculty Publications

The increasing abundance of ticks poses a growing public health concern due to heightened human exposure to tick bites. The lone star tick (Amblyomma americanum: Ixodida: Ixodidae), a common human-biting species in the United States, has expanded its range in recent years. However, how its different life stages vary across time, habitats, and locations remains insufficiently understood. We analyzed tick abundance data collected in southeastern Virginia between 2009 and 2018, focusing on larval, nymphal, and adult life stages. A Bayesian multivariate modelling framework was used to examine seasonal patterns, habitat effects, spatial variation, and biological links between life stages. Two …

Variable Infections But No Evidence Of Immune Priming In Bumble Bee Hosts Against Novel Exposure To A Honey Bee Virus, Austin C. Calhoun, Ben M. Sadd

Faculty Publications – Biological Sciences

Ongoing global change presents novel challenges to species persistence, including heightened emerging infectious disease (EID) exposure. While invertebrates lack vertebrate acquired immunity, many species exhibit “immune priming” with enhanced protection to repeated pathogen exposures. This phenomenon could be critical for species of conservation concern, such as for wild bumble bees, where EID risk is amplified through contact with managed bee pollinators. We investigate the potential for immune priming against the honey bee-derived Israeli Acute Paralysis Virus (IAPV) in Bombus impatiens bumble bees. We test the hypothesis that prior pathogen-associated exposure affords greater resistance and tolerance upon secondary pathogen exposure, due …

Granulomatous Cellular Signatures In Nontuberculous And Tuberculous Mycobacterial Infections, Brianna M. Doratt, Ethan G. Napier, Mahdi Eskandarian Boroujeni, Sarah Douglas, Michael H. Davies, Luiz Bermudez, Eliot Spindel, Erin F. Mccaffrey, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM) are acid-fast bacilli that trigger granuloma formation, a hallmark immune response aimed at containing infection. While the biology of Mtb granulomas has been widely investigated, far less is known about granulomas caused by NTM infection, despite the increasing prevalence and clinical challenge of NTM cases worldwide. Because granulomas influence infection control, pathology, and treatment response, understanding their cellular organization and signaling is critical to improving therapeutic strategies. Therefore, we characterized granulomas formed following infection of rhesus macaques with Mycobacterium avium subsp. hominissuis (MAH) and compared them to granulomas from cynomolgus macaques infected with …

Glycoprotein-Specific Transcriptional Response Contributes To Differential Vaccine Protection Against Lethal Ebola Virus Infection, Sheridan B. Wagner, Delphine C. Malherbe, Ethan G. Napier, Andrea Marzi, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Since the West African Ebola virus (EBOV) epidemic in 2014-2016, recurrent outbreaks of the EBOV-Makona variant have been driven by recrudescence and human-to-human transmission emphasizing the need for effective vaccination strategies. A live-attenuated recombinant vesicular stomatitis virus (VSV)-based vaccine expressing the EBOV-Kikwit variant glycoprotein (VSV-Kik) received FDA approval in December 2019 and provides complete, rapid protection against EBOV-Makona as early as 7 days post-vaccination (DPV). During the 2018-2020 Ebola outbreak, the VSV-Kik vaccine, known as ERVEBO, was administered to lower-risk individuals at a 5-fold dose reduction of the standard 2 × 10 ⁷ PFU to provide broader population protection. Identification …

The Rhesus Macaque Model Of Mycobacterium Avium Infection Reveals That Age-Related Disease Is Due In Part To Chronic Inflammation And Lung Microbial Dysbiosis, Ethan G. Napier

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Aging is associated with dysregulated immunity and increased susceptibility to infection, a phenomenon dubbed as immunosenescence and characterized by reduced naïve T and B cell pools, altered innate immune function, and chronic low-grade inflammation. Nontuberculous mycobacterial (NTM) pulmonary disease (NTMPD) is an increasingly relevant chronic lung infection that disproportionately affects older adults (65+ years) and immunocompromised individuals. However, the host factors underlying increased disease severity in aged patients remain poorly defined. Literature suggests that effective control of NTM relies on coordinated innate and adaptive immune responses, particularly macrophage activation and Th1 cytokine signaling. Using a rhesus macaque model that closely …

A Framework For Characterizing The Peripheral Immune Isonome Using Long-Read Single-Cell Rna Sequencing And Its Relevance To Neurological Disease, Patricia Hayes Doyle

Theses and Dissertations--Neuroscience

Long-read single-cell RNA sequencing provides an opportunity to understand human health and disease at isoform resolution, revealing cellular diversity and disease mechanisms difficult to resolve with bulk or short-read methodologies.

Using a modified PIPseq workflow and computational pipeline adapted for Oxford Nanopore (ONT) sequencing, we profiled isoform usage across immune cells, integrating marker expression and isoform discovery, generating the largest long-read single-cell dataset of human immune cells from a single individual to date. We identified non-canonical protein-coding variants of GZMB and CD3G enriched in unexpected cell types. We also discovered novel transcripts from CMC1 and LYAR with cell-type-specific signatures that …

Equid Major Histocompatibility Complex (Mhc) Evolution & Genome Organization, Lauren C. Johnson

Theses and Dissertations--Veterinary Science

The evolution of modern horses has a well-documented fossil record and has long been of interest to the genetics community. Although non-caballine equids (e.g. zebras, donkeys, and asses) can hybridize with horses, the resulting offspring are typically infertile. Despite these reproductive barriers, genomic analyses reveal regions of high sequence similarity among equid species. This dissertation investigates the role of historical introgression in the evolution of modern Equus species. The first chapter re-evaluates earlier findings derived from a limited horse population and a single reference genome. The variants of the identified regions were pushed through Ensembl’s Variant Effect Predictor to assess …

Evaluation Of Mycoplasma Genitalium Positivity And Co-Infection With Chlamydia Trachomatis And/Or Neisseria Gonorrhoeae At Various Care Sites Across The United States, Rebecca Lillis, Rodney Arcenas, Christy M. Boraas, Steven E. Chavoustie, Lashonda Crane, Nicole D'Empaire, Aaron C. Ermel, Glenn Harnett, Federico Hinestrosa, Stacey House, Joseph Miller, Anthony Mills, Ronald Poblete, Stephen Young, Barbara Van Der Pol

School of Medicine Faculty Publications

OBJECTIVES: We evaluated Mycoplasma genitalium (MG) positivity and co-infection with Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG), based on results from a trial assessing clinical performance of the Cobas® Liat CT/NG/MG point-of-care test. METHODS: A prospective, US, multicenter, noninterventional study assessed MG positivity in prospective urine samples (male) and clinician-collected vaginal swabs (female) from symptomatic/asymptomatic patients aged ≥14 years attending various clinical settings. Participants were designated positive or negative for MG, CT, and NG based on combined results from three US Food and Drug Administration-approved assays and one laboratory-developed test. MG co-infection with CT and/or NG was assessed. RESULTS: Among …

Nanosecond Electric Pulses As A Novel In Situ Vaccination Strategy For Cancer Treatment: Mechanisms, Challenges And Prospects, Siqi Guo

Bioelectrics Publications

Nanosecond electric pulses (nsEPs) are an emerging pulsed-power technology with unique bioelectric characteristics distinct from conventional long-pulse electroporation. As a tunable physical modality, nsEPs can modulate intracellular structures, membrane dynamics, and signaling pathways. Increasing evidence supports nsEPs as a promising non-thermal tumor ablation approach due to their high spatial precision, preservation of critical tissue structures, and minimal adverse effects. One of the most significant discoveries associated with nsEP tumor ablation is the induction of potent systemic antitumor immunity, particularly in situ vaccination (ISV) effects and, in some cases, abscopal effects against distant untreated tumors. Substantial evidence demonstrates that nsEPs can …

Computational And Ai Frameworks For Identifying Key Regulatory Genes And Their Target Genes In Plants And Humans, Md Khairul Islam

Dissertations, Master's Theses and Master's Reports

This dissertation presents computational and AI-driven frameworks for identifying key regulatory genes and their downstream targets across plant and human biological systems. Three studies address distinct challenges in genomic regulation using advanced machine learning and bioinformatics approaches.

The first study introduces DyGAF (Dynamic Gene Attention Focus), a dual-attention transformer framework that identifies and ranks disease-relevant biomarker genes by simultaneously modeling independent molecular responses and interdependent regulatory network behavior. Two attention models provide complementary perspectives on gene importance and are fused through a novel combination metric. Applied to COVID-19 nasopharyngeal swab profiles, the attention-weighted representations achieved 94.23% classification accuracy, high sensitivity, …

A Novel Tyrosine Kinase Axis In Innate Immune Signaling, Santanu Das, Pracheta Sengupta, Manoj Veleeparambil, Saurabh Chattopadhyay

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Tyrosine phosphorylation has emerged as a central regulatory mechanism in innate immunity. Building on our recent studies that Syk and EGFR sequentially phosphorylate TLR9 to fully activate it, we discuss how similar mechanisms operate across other Toll-like receptors and the cytosolic DNA sensor STING. Evidence from complementary systems reveals that receptor and nonreceptor tyrosine kinases, including Src-family kinases, Syk, BTK, and EGFR, form an integrated signaling network that triggers receptor activation, trafficking, and downstream gene expression. Scavenger receptors such as SR-A further drive this kinase cascade by coordinating viral recognition to TLR activation. These observations reveal a novel ‘tyrosine kinase …

Bariatric Surgery Impacts Immune Cell Metabolism And Function Dependent On Metabolic Status, Samantha N. Hart

University of Kentucky Doctoral Dissertations

Type 2 Diabetes (T2D), one of the top ten causes of death worldwide, is fueled by chronic inflammation. T2D is considered a metabolic disease, and there is a great push to target metabolic and associated inflammatory pathways to ameliorate the disease & its comorbidities i.e., obesity and cardiovascular disease. Thus far, clinical trials of anti-inflammatory drugs have had modest impacts on T2D and have not led to changes in clinical practice. This may in part be due to a gap in knowledge in the mechanism(s) driving obesity-associated chronic inflammation. I posit that metabolic abnormalities in immune cells in those with …

A Phylogenetic Analysis Of Avian-Associated Ixodes Scapularis & Implications For Lyme Disease, Nora Correiro

Honors Theses

Lyme disease, caused by the bacterium Borrelia burgdorferi and transmitted by the blacklegged tick Ixodes scapularis, is the most common vector-borne illness in the United States. Whereas Lyme disease is concentrated in the northeastern US, I. scapularis exists in the southeast as well, and the ticks in these regions generally separate into northern and southern evolutionary lineages. Although recent analyses suggest unidirectional and limited gene flow from north to south due to behavioral, ecological, and environmental barriers, the mechanisms underlying the persistence of this limited gene flow remain unclear. This study examines whether bird-mediated dispersal may facilitate south-to-north gene …

Elevated Temperatures Disrupt Wolbachia-Induced Feminisation And Reshape Microbial Community Dynamics Across Generations In A Spider Host, Virginija Mackevicius-Dubickaja, Jennifer A. White, Ellen E. Williams, Eyal Klement, Yuval Gottlieb, Matthew R. Doremus

Entomology Faculty Publications

Longitudinal microbial interactions within a host are challenging to study, leading to a focus on constructed microbial communities in vitro settings. Here, we take advantage of a naturally defined microbial community within a spider host to study how elevated temperatures influence microbial dynamics and phenotypes across host generations. The spider Mermessus fradeorum hosts up to five endosymbionts, including a Wolbachia strain, W1, which induces feminisation, causing genetic males to develop as phenotypic females, skewing sex ratios and promoting symbiont spread. Despite this, Wolbachia 1 persists at intermediate frequencies in wild populations. We hypothesised that elevated temperatures might reduce penetration of …

Multi-Omics Analysis Of Immune-Metabolic Adaptation To Direct-Fed Microbial Supplementation In Newly Weaned Beef Steers, Adekunle Odunayo Ajiboye

Graduate Theses, Dissertations, and Problem Reports (ETD)

Immune and metabolic disruption during weaning represents a major challenge to health and productivity in beef cattle. This dissertation tested the hypothesis that supplementation with multi-strain direct-fed microbials (DFMs) modulates immune regulation and metabolic pathways associated with adaptation to weaning stress. To address this, whole-blood transcriptomics and plasma metabolomics were used to evaluate molecular and metabolic responses in newly weaned beef steers during the receiving period. Transcriptomic analysis identified differential expressions of genes associated with immune signaling and inflammatory regulation, indicating modulation of immune-related pathways without changes in growth performance. Metabolomic analysis revealed alterations in circulating metabolites related to amino …

Population Dynamics And Future Viability Of The Eastern Massasauga Rattlesnake (Sistrurus Catenatus) In Southwest Michigan, Matthew John Klein

Graduate Theses, Dissertations, and Problem Reports (ETD)

Managing at-risk species or populations requires understanding the demographic and genetic drivers of long-term population trends. The eastern massasauga rattlesnake (Sistrurus catenatus) is a federally threatened species facing multiple interacting threats across its range. Habitat loss from wetland drainage and agricultural land conversion has caused range contractions and geographic isolation of populations. Because remaining populations are often small and widely separated, most are now genetically isolated, threatening their long-term viability. Reversing these declines requires understanding population dynamics, quantifying extinction risk, identifying drivers of long-term viability, and assessing the effects of inbreeding and the potential for genetic rescue to …

Improving Antibiotic Prescribing For Urinary Tract Infections In Urgent Care Centers, Alexis Alastanos

Graduate Theses, Dissertations, and Problem Reports (ETD)

Introduction: Urinary tract infections (UTIs) are one of the most common infections that require antibiotic therapy. Providers working in three urgent care clinics located in Eastern West Virginia diagnosis and treat UTIs based on their clinical judgement. Variability in clinical judgement results in inappropriate antibiotic use which has implications on antibiotic resistance and the financial burden of the patients as well as the entire organization.

Evidence Review: A total of 10 articles were evaluated to support the implementation of antibiotic stewardship initiatives that provide guidance in caring for this population. Interventions include electronic health record enhancements, provider education, and tracking …

An Assessment Of Disease Risks, Population Genetics, And Spatial Ecology Of Appalachian Cottontails (Sylvilagus Obscurus) And Snowshoe Hares (Lepus Americanus) In West Virginia, Usa, Madison Leigh Miller

Graduate Theses, Dissertations, and Problem Reports (ETD)

Snowshoe hares (Lepus americanus) occupy a large range across the United States and Canada. While snowshoe hare populations are generally considered stable in the interior of their range, populations along range edges are experiencing declines, possibly driven by climate-related factors such as seasonal coat color mismatch. West Virginia represents one of the southernmost extents of the species’ range, yet little is known about the population genetic status or population sizes of snowshoe hares in the state. Appalachian cottontails (Sylvilagus obscurus) are another lagomorph species found in West Virginia. This species experienced a historical decline and currently …

A Transdisciplinary Approach To Advancing Water Security And Public Health: The “Nurse + Engineer” Model For Achieving Sustainability In Wash Systems Using Community-Based Participatory Research, Daniel B. Oerther, Sarah Oerther

Civil, Architectural and Environmental Engineering Faculty Research & Creative Works

Human health is linked to the health of the environment, a concept referred to as planetary health. As environmental challenges become increasingly complex, single-disciplinary approaches are insufficient to achieve sustainable solutions. This article presents a transdisciplinary framework, termed the "Nurse + Engineer" model, as a novel methodology for addressing complex problems at the nexus of environmental engineering and public health. The model integrates the technical design and systems-level thinking of environmental engineering with the community-based, patient-centered care of nursing. This work details the key lessons learned from the retrospective application of this framework to a series of multi-year, community-based participatory …

Development Of A Semi-Mechanistic Pharmacokinetic-Pharmacodynamic Model For Beta-Lactam Antibiotic Combination Against Enterococcus Faecalis Based On Time-Kill Assays To Predict Drug Disposition And Guide Dosing Strategy In A Severe Renal Impairment Population, Ruhma Zia Khan

Selected Full-Text Dissertations 2020-

Bacterial resistance to antibiotics continues to be a global health problem, limiting antibacterial therapy against infective endocarditis caused by Enterococcus faecalis. To overcome increasing resistance, dual beta-lactam therapy has been advocated as an alternative regimen for treatment – the synergistic activity against E. faecalis demonstrated to be effective. Currently, ampicillin plus ceftriaxone is the standard of care, but the practical application of this therapy is limited by ampicillin’s poor stability in solution at room temperature. A synergistic combination of penicillin plus ceftriaxone shows promise due to penicillin’s superior stability at ambient temperature, but ceftriaxone’s potential to cause hepatoxicity further limits …

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), …

Balancing Inquiry Based Learning And Direct Instruction, Sharon Liu , '26

Senior Theses, Projects, and Awards

No abstract provided.

Effect Of Jet Lag And Nighttime Shifts On The Circadian Rhythm Of Humans, Mahd Adrees

Williams Honors College, Honors Research Projects

This project reviews the circadian rhythm and its disruption by jet lag and nighttime shifts. It discusses the effects on melatonin, sleep quality, and physiological symptoms using articles from Google Scholar. Key studies, mechanisms, and statistics will support these points. A discussion follows, comparing and contrasting the various literature sources. This review aims to raise awareness and summarize strategies to reduce jet lag and nighttime shift effects, improving wellbeing.

Repurposing Cyclin-Dependent Kinase Inhibitors For The Discovery Of Novel Antiplasmodial Compounds, Ritam Bhowmik

Honors Undergraduate Theses

Malaria remains a major global health burden with over 282 million cases annually and rising resistance to artemisinin-based combination therapies. Plasmodium falciparum, the most lethal malaria parasite species in humans, relies on tightly regulated cell cycle progression during replication within red blood cells. Cyclin-dependent kinases (CDKs) are central regulators of eukaryotic cell division and transcription, and several CDK-like enzymes in P. falciparum, including Pfmrk and PfPK6, are essential for parasite growth and structurally distinct from human kinases. This study evaluated whether commercially available human CDK inhibitors (CDKIs) targeting cancer pathways could be repurposed as novel antimalarial compounds. A library of …

Impact Of Lifestyle Factors On Allergic Rhinitis Symptoms And Quality Of Life Among College Students, Lina Saint-Hilaire

Honors Undergraduate Theses

This study aims to examine the influence of certain lifestyle factors on the presentation of allergic rhinitis symptoms and the quality of life of college students. Factors of interest include residential setting, household cleaning habits, age of symptom onset, and exposure to household pets. Additional analysis includes assessment of the impact of allergic rhinitis symptoms on sleep. Using a cross-sectional survey design, student responses were self-reported through a paper survey distributed during tabling days at the University of Central Florida (UCF) main campus. Eligible participants had to be 18 years or older and current UCF graduate and undergraduate students. Survey …

Investigating The Interaction Of Gram-Positive Lactobacillus Species With Mucin In The Context Of Barrett's Esophagus, Ritisha Suresh

Honors Undergraduate Theses

Gastroesophageal Reflux Disease (GERD) can progress to the precancerous Barrett’s Esophagus (BE) condition, in which the normal esophageal squamous epithelium is replaced with a columnar epithelium containing goblet cells. Mucins, sticky substances, are secreted in response to bile acid exposure during reflux episodes to protect the esophageal epithelium. Goblet cells secrete these mucins, which can also scaffold microbial colonization. Probiotic Lactobacillus bacteria can use glycosidase enzymes to process mucin and metabolize them into their component sugars (glycans). This project aims to identify the role of the Lactobacillus-mucin interaction in BE, as glycan availability could confer an advantage to Lactobacillus …

The Role Of Dromedary Camels In The Pprv Epidemiology: Episystem Possibility And Evidence Supporting Global Eradication., Reham Karam, Mahmoud S. Safwat

Mansoura Veterinary Medical Journal

Background: Peste des petits ruminants (PPR) is a notifiable, highly contagious and transboundary viral disease infecting a wide range of domestic and wild ruminant species and is caused by a morbillivirus. The disease represents a major predisposing factor of poverty in many endemic regions. Although global eradication of PPR is an internationally endorsed objective, achieving this goal has become increasingly challenging due to the expanding host range of the virus. Methods: Narrative review methodology was used and SANRA criteria to access reliability and quality of the methodology. focuses on PPR infection in camels, which has been reported in some instances …

To Flea Or Not To Flea: Abiotic And Biotic Factors Driving Flea Parasitism On Wild Deer Mice, Parker Todd, Angela Luis, Mike Kinsella

Undergraduate Theses, Professional Papers, and Capstone Artifacts

Deer mice (Peromyscus maniculatus) are an abundant North American rodent and the primary reservoir for Sin Nombre virus (SNV), a hantavirus with a 30-40% case fatality rate in humans. While ectoparasites, such as fleas, are not considered vectors of SNV, their bites may indirectly affect the transmission of SNV by impacting host condition or immune function. These impacts could potentially lead to an increase in host susceptibility and/or an increase in viral shedding, yet there is still little knowledge on what influences flea parasitism on deer mice in western Montana. This study looks to examine how mouse sex, …

The Sub-Lethal Effects Of Trematode Parasites On The Migratory Behavior Of Lesser Scaup (Aythya Affinis), Scott Alan Herman

Graduate Research Theses & Dissertations

The introduction of the invasive freshwater faucet snail (Bithynia tentaculata) and its associated parasites in the Upper Mississippi River and Great Lakes Region provides the opportunity to investigate how anthropogenic stressors impact the life history of lesser scaup (Aythya affinis) using the Mississippi Flyway. To understand the life histories and interactions between lesser scaup and faucet snails we examined historical records, research, and ecology textbooks. Our literature review identified critical knowledge gaps in lesser scaup literature surrounding population dynamics, reproduction, and migration. Specifically, the sub-lethal effects of invasive trematodes on the migratory behavior of lesser scaup in the Upper Mississippi …