Novel Biomarker Discovery In Multiple Sclerosis, Manisha Gangasani

Honors Theses

Multiple Sclerosis (MS) is a chronic neuroinflammatory disorder affecting the brain, spinal cord, and optic nerve. Patients experience cognitive, motor, autonomic, and emotional symptoms that often overlap with other neurological conditions, making early diagnosis challenging. Current diagnostic criteria require evidence of lesions with dissemination in time and space. Racial disparities in MS outcomes are well documented, with Black individuals often exhibiting greater disease severity, higher relapse rates, and increased disability compared to White individuals. These differences likely reflect a combination of genetic, biological, environmental, and healthcare access factors, underscoring the need to improve early diagnosis and reduce inequities in care. …

Determining Zap-70 Signaling Pathways Mediated By Ccr7 In Tcr T Cell Activation, Vivian Torres

Open Access Theses & Dissertations

Activation of T lymphocytes is the main event that occurs in the adaptive immune response after engagement of the T cell receptor (TCR) with the peptide of the major histocompatibility complex (pMHC) molecules that are demonstrated by antigen presenting cells [1]. A key step in this process is the recruitment and activation of the zeta chain associated protein of 70 kDa (ZAP-70). ZAP-70 couples TCR engagement to downstream intracellular signaling pathways through phosphorylation of tyrosine residues within intracellular tyrosine activation motifs (ITAMs) [2]. Although there have been extensive studies on the signaling response through TCR activation, the regulatory influence of …

Identification And Preclinical Assessment Of Novel Therapeutic Modalities In Environmental Exposure-Induced Lung Disease, Aaron D. Schwab

Theses & Dissertations

Environmental lung diseases are preventable respiratory conditions either caused or made worse by inhaled environmental exposures. Contemporarily, environmental lung diseases are most associated with workplace exposures given specific occupational processes aerosolize inflammatory agents that can be inhaled at high concentrations. Although a considerable amount is known regarding immunoglobulin (Ig)E-mediated responses to environmental exposures, little is known about non-IgE mediated respiratory conditions resulting from lipopolysaccharide (LPS)-enriched organic dust exposure(s). Chronic respiratory diseases such as asthma, hypersensitivity pneumonitis, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis have all been identified as environmental lung diseases caused or exacerbated by such environmental dusts. Therapeutic …

Natural Killer T Cell-Mediated Control Of Francisella Tularensis-Induced Cytokine Storm Syndrome, Cameron M. Torres

Open Access Theses & Dissertations

Inflammation is critical for the effective clearance of viral and bacterial challenges, while simultaneously a mechanism utilized by many highly infectious pathogens to cause disease. The bacterium Francisella tularensis, the causative agent of human tularemia, elicits a cytokine storm, wherein the immune system over-responds to the presence of the bacterium causing a dysregulated release of proinflammatory and regulatory cytokines. Without treatment, tularemia mortality can be as high as 30%, with inhalation of as few as 10 CFUs inducing respiratory tularemia. Natural Killer T (NKT) cells are innate-like T lymphocytes with a diverse array of regulatory functions. Unlike conventional T cells, …

Intratumoral Fibrin As A Novel Immunomodulatory Factor In Pancreatic Ductal Adenocarcinoma, Mazharul Karim

Open Access Theses & Dissertations

In-situ coagulation is a common clinical feature of pancreatic ductal adenocarcinoma (PDAC) that presents a highly thrombotic and crosslinked insoluble fibrin (x-fibrin)-laden tumor stroma (FibTS). However, the specific impact of FibTS on immune cells behavior remains largely unexplored in this poorly infiltrated tumor. We aimed to elucidate how FibTS in PDAC regulates immune cell infiltration, polarization, and crosstalk that favors immunosuppressive microenvironment and tumor growth. We characterized human PDAC tissues by multiplex immunostaining and checked the spatial distribution of immune cells based on the presence of x-fibrin. We investigated how FibTS influences the infiltration of tumor-associated macrophage (TAM) and T-cell …

Ccr7 Regulated Mechanisms That Limit The Adaptive Immune Response, Jaisel Amilcar Cervantes

Open Access Theses & Dissertations

C-C chemokine receptor 7 (CCR7) is critical in guiding T cell migration within the thymus and peripheral lymphoid tissues, shaping the adaptive immune response by promoting central tolerance and regulating immune homeostasis. Although its role in lymphocyte trafficking is well established, the molecular mechanisms by which CCR7 influences thymocyte development and T cell receptor (TCR) repertoire formation remain less understood. This study examines how CCR7 deficiency impacts thymic selection, TCR diversity, and the signaling events that shape repertoire restriction. Using a homozygously deleted CCR7 murine model, we found that the absence of CCR7 results in a less restricted TCR repertoire …

Resilience And Reality: Exploring The Lived Experiences Of People Living With Hiv In Texas During The Covid-19 Pandemic – A Qualitative Study., Ahmed F. Alanazi

Social Work Dissertations - Archive

This study investigated the lived experiences of individuals living with HIV (PLWH) in the Dallas-Fort Worth (DFW) area of Texas during the COVID-19 pandemic, using an Interpretative Phenomenological Analysis (IPA) framework. The research examined the intersection of health, social dynamics, and psychological resilience among PLWH, who faced compounded vulnerabilities due to systemic inequities and the dual public health crises of HIV and COVID-19. Through semi-structured interviews with ten participants from diverse backgrounds, the study captured the profound impacts of disrupted healthcare systems, heightened stigma, and social isolation on this marginalized population. The findings reveal that the pandemic exacerbated existing inequities …

Leveraging Clinical Standards To Improve The Translational Relevance Of Therapies For Experimental Spinal Cord Injury, Aaron L. Silverstein

Theses and Dissertations--Neuroscience

Efforts to improve treatment of spinal cord injury (SCI) often use animals to develop effective therapeutics, intending to improve the survival and the quality of life of persons with SCI. Over half of all SCIs in the United States occur at the cervical level and often cause locomotor deficits and life-threatening breathing dysfunction. Thus, my dissertation is focused on this important patient population.

After beginning with a description of translational research and surveying SCI from a clinical standpoint, I turned to describe experimental models of cervical SCI and more detailed neuroimmunological findings relevant to my work. Then, I conducted a …

Implementing The Methodology To Generate Diagnostic And Therapeutic Antibodies, Andrea Mariana Carlin

Open Access Theses & Dissertations

This research aimed to establish the methodology for developing monoclonal antibodies at The University of Texas at El Paso. Monoclonal antibodies are indispensable across multiple fields, including diagnostics, therapeutics, and biotechnology, yet there is a shortage of commercially available antibodies targeting specific proteins or possessing specialized characteristics. To address this gap, three models were selected: a peptide derived from the intracellular protein Schlafen 8 and two cell surface protein receptors: mouse vascular endothelial growth factor receptor 2 (VEGFR2) and human melanocortin receptor 4 (MC4R). These proteins present unique challenges in antibody generation, including issues of accessibility, expression, and specificity.

Throughout …

Enhancement Of Zika Virus Infection By West Nile And Dengue Virus Antibody Positive Cord-Blood Samples From Mothers In El Paso-Texas, Jeanette Orbegozo

Open Access Theses & Dissertations

The recent Zika virus (ZIKV) outbreak and its association with microcephaly cases and other neurological syndromes are important public health concerns. A phenomenon known as antibody-dependent enhancement (ADE) involves preexisting flavivirus antibodies to a specific flavivirus that enhances the severity of a second infection with a different flavivirus. Since ZIKV is related to flaviviruses like West Nile virus (WNV) and dengue virus (DENV), prior exposure to these viruses could elicit cross-reactive antibodies that may enhance a subsequent ZIKV infection. Therefore, this study aimed to determine if WNV and DENV antibodies from cord blood enhanced ZIKV infection in vitro. Initially, a …

Novel Therapuetic Approaches For Chagas Disease, Juan Carlos Silva

Open Access Theses & Dissertations

Chagas disease (CD) is caused by the hemoflagellate protozoan Trypanosoma cruzi. This disease is considered one of the 20 neglected tropical diseases (NTD), and it is estimated that 6 to 8 million people worldwide are diagnosed with CD. In the United States, Chagas infection is not reported in all states; however, most reported CD cases are chronic infections. Chagas infection is characterized by two phases: an acute and a chronic phase. Until this present moment, no prophylactic or therapeutic human vaccine is available. However, in a recent study in a murine model, our group showed that the synthetic 20-merpeptide (DAENPGGEVFNDNKKGLSRV) …

Selective Transfection Of A Transferrin Receptor-Expressing Cell Line With Dna-Lipid Nanoparticles And Synthesis Of Parasite-Derived Glycans As Biomarkers For Leishmaniasis, Irodiel Vinales Lozano

Open Access Theses & Dissertations

Despite notable progress in lipid nanoparticle (LNP)-mediated gene delivery, achieving selective transfection of specific cell types, such as cancer cells, remains a significant hurdle, hindering the advancement of innovative gene therapies. In this study, we engineered an LNP formulation encapsulating plasmid DNA (pDNA) encoding the monomeric Green Lantern (mGL) fluorescent reporter protein. The DT7 peptide ligand targeting human transferrin receptor 1 (hTfR1) was also conjugated to the LNP surface for targeted delivery to hTfR1-expressing cells. Optimization of LNP composition yielded favorable particle diameter, ζ-potential, yield, and pDNA encapsulation efficiency. Evaluation of transfection selectivity using a panel of two engineered cell …

Food Allergies, The Immune Response, And Preventative Treatments: Milk, Egg, And Shellfish Allergies, Marissa Dimatteo

Undergraduate Honors Theses

Food allergies have been an increasing concern worldwide with very little information on preventative measures and treatment. They can have long lasting and life-threatening consequences with a wide range of symptoms from hives to anaphylactic shock. Long recommended feeding guidelines, vitamin and mineral deficiencies, and gastrointestinal alterations are thought to play a role in the increase in food allergies in infants. Early introduction of food, immunotherapy, and a properly supported gut microbiome have been recommended to decrease the likelihood of developing a food allergy and desensitizing the immune system.

Repolarizing Tumor-Associated Macrophages In Ovarian Cancer: A Novel Immunotherapeutic Approach, David Schweer

Theses and Dissertations--Clinical and Translational Science

Ovarian cancer, recognized for its high lethality and resistance to conventional immunotherapies, mandates innovative strategies to confront its intricate challenges. The tumor microenvironment (TME), orchestrated by tumor-associated macrophages (TAMs), assumes a pivotal role in disease progression, rendering TAMs an appealing therapeutic target. This study endeavors to explore the prospect of repolarizing TAMs from a protumor M2 phenotype to an antitumor M1 state, employing M1 macrophage-derived vesicles (MEVs) as a groundbreaking immunotherapeutic approach.

The primary objective is to investigate the capacity of M1 MEVs to repolarize M2 macrophages in vitro towards an anti-tumor M1-like phenotype. By inducing human macrophages to adopt …

Neural Damage Following Francisella Tularensis Infection, Anahis Tena

Open Access Theses & Dissertations

This dissertation investigates the impact of Francisella tularensis infection on the brain, focusing on its anatomical localization, effects on synaptic health, and behavioral and cognitive consequences in mice. Employing a combination of fluorescent tagging, confocal and light sheet microscopy, the study first maps bacterial foci within the brain, anticipating a concentration in the limbic system, particularly the hippocampus. Subsequently, it examines synaptic function post-infection using calcium imaging in various neuronal cultures, expecting a decrease in calcium signaling indicative of synaptic impairment. Finally, behavioral assays like the forced swim test, object recognition test, and Morris Water Maze assess the cognitive and …

Evaluation Of The Efficacy Of Synthetic Glycovaccines Against Both Murine Acute Chagas Disease And Cutaneous Leishmaniasis, Colin D. Knight

Open Access Theses & Dissertations

Chagas disease (CD) and cutaneous leishmaniasis (CL) are neglected tropical diseases caused by the protozoan trypanosomatids, Trypanosoma cruzi and Leishmania spp., respectively. There are approximately 6-8 million people infected with T. cruzi worldwide and ~300,000 people in the US. Between 700,000 and 1.2 million new cases of CL occur worldwide yearly. The approved chemotherapies for both diseases are partially effective and may cause serious adverse events, resulting in premature treatment interruption. Moreover, no effective vaccine for either disease is available. Therefore, developing a vaccine that would provide effective cross-protection against both diseases would provide a cost-effective alternative to the existing …

A Novel Neuroinvasive Infection Modality For Francisella Tularensis Elicits Neuroinflammation Resulting In Cellular Damage, Mireya Griselle Ramos-Muniz

Open Access Theses & Dissertations

Francisella tularensis (Ft.) is a gram-negative coccobacillus bacterium that causes the zoonotic disease tularemia in humans. Ft. causes the most severe, often fatal, form of the disease through inhalation. However, Ft. is most commonly transmitted through direct contact with infected animal carcasses such as rodents and rabbits, consumption of contaminated food or water, or through arthropod bites, particularly ticks. Due to its extremely low infectious dose, high mortality rate, and potential use as a biological warfare agent, Ft. is classified by the CDC as a "Tier 1 select agent". Ft. infection triggers an overactive inflammatory response, termed a "cytokine storm", …

The Management Of Non-Ige-Mediated Allergies In Human Milk-Fed Infants, Sarah Kelly Rowe

Graduate Theses

Background: Non-IgE (immunoglobulin E)-mediated food allergies (FA) present diagnostic and management challenges despite guidelines due to knowledge gaps amongst clinicians. Given that 60% of food protein-induced allergic proctocolitis (FPIAP) cases occur in breast-fed infants, maternal elimination diets are routinely prescribed to manage allergy symptoms. The implications of maternal dietary eliminations extend beyond maternal nutrition to consideration of infant nutrition and feeding skill acquisition.

Methods: A survey-based retrospective, cross-sectional study sought to identify dietary triggers and symptom management techniques practiced by (n=59) lactating mothers of infants with confirmed and suspected cases of non-IgE FA in the United States. Statistical significance was …

Isoprenylation Inhibition Significantly Reduces Ige Mediated Mast Cell Function And Allergic Disease, Jordan Dailey

Theses and Dissertations

Allergic disease is the 6^th leading cause of chronic illness in the US and accounts for billions of dollars in healthcare annually. Mast cells are tissue resident innate immune cells linked to allergic disease and activated by IgE and other ligands. Upon activation, they release histamine, cytokines, chemokines, proteases, and lipid mediators evoking allergic symptoms. New ways of targeting mast cells could greatly benefit allergic disease therapy. Previous findings supported repurposing statin drugs, such as Fluvastatin, as a therapeutic treatment of allergic disease reduced allergic symptoms in vitro and in vivo. We found that Fluvastatin suppressed IgE-mediated mast cell …

Intrinsic Cardiac Effects Of Severe Acute Respiratory Syndrome Coronavirus 2 In Coronavirus Disease 2019, Brittany Danielle Brumback

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cardiac arrhythmias, particularly ventricular arrhythmias, can be life-threatening and caused by both congenital genetic mutations and acquired cardiac injury. My thesis work was originally focused on delineating the effects of genetic mutation-driven dysregulation of a protein called Hey2 in Brugada Syndrome, a complex disease characterized by a predisposition to dangerous arrhythmias originating in the right ventricular outflow tract. In response to the pandemic, my thesis work shifted toward understanding the mechanisms of cardiovascular injury in Coronavirus disease 2019 (COVID-19), which is associated with serious cardiovascular complications, including ventricular arrhythmias and sudden cardiac death as well as endothelial dysfunction and coagulopathies. …

Defining The Cooperation Between Mhc-I And Mhc-Ii Neoantigen-Driven T Cell Responses To Develop Effective Personalized Immunotherapies, Charmelle Williams

Dissertations and Theses (Open Access)

Immune checkpoint therapy (ICT) (e.g. anti-CTLA-4 (α-CTLA-4), anti-PD-1 (α-PD-1)) enables durable T cell-dependent anti-tumor immunity in certain cancer patients. Since a subset of patients respond to ICT, this work aims at developing a more in-depth understanding of T-cell responses to MHC class I (MHC-I) and MHC class II (MHC-II) tumor antigens that are derived from aberrant expression of non-mutant antigens or driver and passenger somatic alterations that can function as tumor neoantigens. We used a poorly immunogenic Braf^v600e Pten^-/- Cdkn2a^-/- YUMM1.7 (Y1.7) murine melanoma line with a paucity of endogenous neoantigens that is unresponsive to ICT, and …

Clarifying Drug Reaction Terminology: Insights From Deaf College Students Allergic To Penicillin, Andrew Makarewicz

Undergraduate University Honors Capstones

Penicillin is considered to be the most frequently reported drug allergy, with roughly 10% of the U.S. population reporting an allergy (Lee, 2020; Sakoulas et al., 2019). However, current research suggests that more than 90% of people who report a penicillin allergy are actually not truly allergic (Blumenthal et al., 2015; Pongdee & Li, 2018). Confusion about side effects and allergic responses is a common way for penicillin allergies to be falsely reported (Stone et al., 2020). The Deaf community may experience this confusion at a higher rate due to health literacy barriers that likely hinder their learning and understanding …

Addressing The Inpatient Penicillin Allergy: Implementing A Nurse-Driven Allergy Assessment Tool To Enhance Antimicrobial Stewardship., Shelby Ryan Bliss

DNP Projects

Background: In an acute care setting, more than half the inpatient population receives antibiotics. Approximately 10% of the general population reports an allergy to penicillin. It has been replicated in the literature with data that of those who report a penicillin allergy, up to 95% are incorrectly identified. When a patient is admitted to the hospital with a penicillin allergy on their electronic health record, they are at higher risk for adverse events such as a hospital acquired infection, the occurrence of an antibiotic resistant bacteria related to receiving broader therapy and increased healthcare utilization.

Purpose: The purpose of this …

Increasing Staff Awareness And Screening Practices For Adverse Childhood Experiences At A Primary Care Clinic, Kayla Wright

Doctor of Nursing Practice Projects

Adverse childhood experiences (ACEs) are present in approximately 60% of the adult population in the United States. There is a correlation between adverse childhood experiences and chronic health conditions as adults. Despite the evidence showing this correlation, there is a lack of screening for ACEs in the primary care setting. Many primary care providers and staff are unaware of ACEs or the correlation with chronic health conditions and substance abuse and, therefore, do not understand how to or recognize the benefits of screening in primary care. With education for providers and staff, primary care is the ideal setting to perform …

Managing Pediatric Atopic Dermatitis In The Allergy Clinic: Use Of An Eczema Action Plan To Improve Caregiver Understanding And Self-Efficacy, A Pilot Study, Danielle Hubacek

Doctor of Nursing Practice Final Manuscripts

Eczema, or atopic dermatitis, is a complex and chronic condition that affects approximately 10% of children throughout the United States (Brown et al., 2018). The American Academy of Allergy Asthma & Immunology (AAAAI) (2017) estimates the average cost of eczema management for each patient is approximately $3,302 per year. The complex nature of atopic dermatitis indicates a need for individualized treatment plans. Research has shown that standardized patient teaching, written education materials, and Eczema Action Plans (EAP) reinforce patient teaching, parental understanding, and improve quality of life. This evidence-based practice (EBP) project introduces the use of a written Eczema Action …

Suppression Of Inflammation Of Cytokine Following Induced Francisella Tularensis Infection, Nicole Renee Setzu

Open Access Theses & Dissertations

Francisella tularensis is intracellular bacteria which is the causative agent of the disease Tularemia. Highly virulent in both humans and animals, it takes only as few as 10 microorganisms to cause a lethal infection. The bacteria can enter via direct or indirect routes causing the activations of the host innate inflammatory response to ensue. The bacteria invade host dendritic cells and neutrophils but predominately macrophages. This causes a mass inflammatory response resulting in the cytokine storm. Activation of Natural Killer T (NKT) cells has been shown to suppress inflammation in in vivo studies. Development and optimization of an in vitro …

Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb

Electronic Theses and Dissertations

Myeloid-derived suppressor cells (MDSCs) numbers increase significantly in sepsis and are associated with high mortality rates. These myeloid cell precursors promote immunosuppression, especially in the late (post sepsis) stage. However, the mechanisms that underlie MDSC expansion and programming are not completely understood. To investigate these mechanisms, we used a cecal-ligation and puncture (CLP) mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive phase. Previous studies in our laboratory showed that microRNA (miR)-21 and miR-181b elevate levels of the transcription factor nuclear factor 1 (NFI-A) that promotes MDSC expansion. We report here that miR-21 …

What Are The Rhetorical Strategies And Consequences Of Food Labels Regarding Health, Lifestyle, And Ethics Of Consumers With Food-Related Diseases And Allergies?, Delaney Borchers

Master of Arts in Media and Communication Plan II Graduate Projects

In this study, it is investigated on how health, lifestyle and ethical factors of a consumer with a gluten-related disease and allergy influence their understanding and awareness of gluten-free food labels. This study was implemented through an online survey on a Facebook support group with a total of 195 respondents. The results show that consumers do have a strong awareness and understanding of the differences between certified gluten-free and non-certified gluten-free food labels. This indicates that having this strong awareness and understanding is influenced based upon a consumer’s health, lifestyle and ethical factors of following a gluten-free diet.

The Innate Immune Response To House Dust Mite In Allergic Airway Inflammation, Madelyn Miller

Electronic Theses and Dissertations, 2020-2023

House dust mite (HDM) is an indoor aeroallergen which is commonly associated with the development of allergic rhinitis and allergic asthma. In fact, up to 70% of allergic asthmatic individuals have been shown to demonstrate reactivity towards HDM allergens. The downstream adaptive immune response to HDM is well characterize and is described as being largely T helper cell type 2 (Th2) and partly T helper cell type 17 (Th17) dominated. However, less is known about how resident antigen presenting cells (APCs) and structural cells such as airway epithelial cells recognize and respond to HDM. Unlike other microbial antigens, recognition of …

Association Of A Repetitive Manual Task On Inflammatory Biomarker Expression, Heart Rate Variability And Rating Of Perceived Exertion, Daniel Conde

Open Access Theses & Dissertations

The National Institute for Occupational Safety and Health (NIOSH) defines work related musculoskeletal disorders (WMSDs) as a group of disorders involving muscles, tendons, and nerves. The WMSDs symptoms are considered the most common occupational disease, causing limitations in daily activities. Even though there is an association between repetitive manual tasks involving short work cycles, force demanding tasks, and the development of WMSDs, the specific cause of the physiological changes over a long period of time is a cause of debate. The study of mechanisms underlying the physiological changes is essential for the early detection, diagnosis, and appropriate management of WMSDs.