Pharmacology Commons^™

Nutrient-Driven Transcription Factor-Dna Interactions And Their Signaling Mechanisms In Metabolic Disease, Evelyn A. Bates

Theses and Dissertations--Nutritional Sciences

Metabolic homeostasis is maintained through tightly coordinated signaling networks that integrate diverse physiological inputs. Central to this regulation are transcription factors, which sense nutrient, hormonal, and vitamin-derived signals and translate them into coordinated gene expression programs. Transcription factor activity is governed by DNA binding, recruitment of coregulatory proteins, and interactions with specific response elements in gene promoters, which allows them to selectively modulate diverse metabolic pathways. Owing to their multifactorial and tunable nature, transcription factors have emerged as promising targets for the treatment and diagnosis of metabolic diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). This dissertation explores the molecular …

Design And Advancement Of Analytical Frameworks For In Vivo Single-Photon Calcium Imaging To Characterize Temporal- And Treatment-Dependent Neural Adaptations To Opioid Exposure And Withdrawal In The Medial Prefrontal Cortex, Alexia R. Alsum Dr.

Theses and Dissertations--Pharmacy

Despite the availability of several approved medications for opioid use disorder (OUD), it remains a significant public health concern characterized by persistent neurobiological adaptations that drive relapse and impede successful recovery. The medial prefrontal cortex (mPFC), a region critical for executive control and decision-making, undergoes pronounced functional changes during chronic opioid exposure and withdrawal, yet the cellular mechanisms underlying these adaptations remain poorly understood. This dissertation aims to investigate longitudinal alterations in mPFC neural activity across opioid exposure and withdrawal using in vivo single-photon calcium imaging and newly developed computational frameworks.

Following standard preprocessing to extract and normalize calcium traces, …

Molecular Mechanisms And Metabolic Consequences Of Glucocorticoid Resistance, Genesee J. Martinez

Theses and Dissertations--Pharmacology and Nutritional Sciences

Glucocorticoids are vital steroid hormones that govern metabolism, stress responses, and immune functions through intricate, tissue-specific mechanisms, both genomic and non-genomic. These hormones bind to the glucocorticoid receptor (GR), which then acts as a transcription factor to modulate gene expression. Chronic elevation of glucocorticoid levels may lead to glucocorticoid resistance, resulting in adiposity, inflammation, and insulin resistance, thereby adversely affecting multiple metabolic tissues. Whether produced endogenously or administered exogenously, excessive, chronic glucocorticoid concentrations impair glucocorticoid signaling. Although there are two primary isoforms of the receptor, GR⍺ and GRβ, only GR⍺ interacts with glucocorticoids.Through the research conducted in this dissertation, we …

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 …

Umbralisib Antagonizes Multidrug Resistance In Abcb1- Overexpressing Cancer Cells, Letao Bo

Theses and Dissertations

Overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1, is a major mechanism of multidrug resistance (MDR) and contributes to chemotherapy failure by reducing intracellular drug accumulation. Umbralisib is a dual inhibitor of phosphoinositide 3-kinase delta (PI3Kδ) and casein kinase 1 epsilon (CK1ε) that was developed for the treatment of hematologic malignancies; however, it was later withdrawn due to safety concerns. In the present study, we found that umbralisib has the potential to reverse ABCB1-mediated MDR. The MTT assay demonstrated that umbralisib significantly sensitized ABCB1-overexpressing KB-C2 and SW620/Ad300 cells, as well as ABCB1-transfected HEK293 cells. Mechanistic assays revealed that umbralisib enhanced …

Identifying Rna Splicing Changes During Alcohol Withdrawal Using An Optimized Rna-Seq Analysis Pipeline, Yasaswi Veera, Luana Martins De Carvalho, Amy Lasek

UROP Posters

Alcohol use disorder (AUD) causes long-lasting changes in brain gene expression and RNA splicing, particularly in the ventral hippocampus. This study analyzes RNA-Seq data from rats exposed to chronic alcohol and withdrawal to identify transcript-level and splicing alterations. An optimized RNA-Seq pipeline using STAR, FeatureCounts, edgeR, and WGCNA improved efficiency by 25-40% while maintaining consistency across 25 datasets. Results reveal changes in neural signaling and stress-response pathways associated with withdrawal. This work provides both biological insight into AUD and a reproducible computational framework for transcriptomic analysis.

Ex Vivo Sensitivity Assays With Molecular Validation To Guide Preclinical Drug Selection For Schwann Cell Tumors, Ethan W. Hass

Graduate Studies Theses and Dissertations 2026

Schwann cells are the glial cell of the peripheral nervous system. They are dependent on receptor tyrosine kinase-mediated RAS signaling, cell matrix adhesion, and cell-cell contact to proliferate during nerve development and repair. These pathways become deregulated with loss of function of the merlin tumor suppressor encoded by NF2, leading to benign tumors called schwannomas. Patients with NF2-related schwannomatosis (NF2-SWN) develop bilateral vestibular schwannomas that cause hearing loss, tinnitus, and death from brainstem compression if untreated. Severe NF2-SWN causes multiple spinal and peripheral schwannomas and neuropathic pain. Schwannomas require careful monitoring, trial and error use of repurposed anti-cancer …