Immunology and Infectious Disease Commons^™

Machine Learning Methods For Pattern Recognition Analysis Of Genomic And Molecular Data, Kuang Du

Dissertations

While immune therapies achieve remarkable success in treating various cancers, only a subset of patients achieves a durable clinical response, and many exhibit innate or acquired resistance. Precision medicine aims to tailor treatments to individual patients based on specific biological markers, ensuring that each patient receives the therapy most likely to be effective. Predictive biomarkers and gene signatures offer potential for more personalized treatment strategies by identifying patients likely to benefit. Recent studies suggest that gene signatures, comprising sets of genes, hold predictive value for certain clinical variables. Typically derived from biological expert knowledge, these signatures demonstrate substantial predictive potential, …

Immune Checkpoint Inhibitor-Associated Cutaneous Adverse Events: Mechanisms Of Occurrence, Abdulaziz M. Eshaq, Thomas W. Flanagan, Abdulqader A. Ba Abbad, Zain Alabden A. Makarem, Mohammed S. Bokir, Ahmed K. Alasheq, Sara A. Al Asheikh, Abdullah M. Almashhor, Faroq Binyamani, Waleed A. Al-Amoudi, Abdulaziz S. Bawzir, Youssef Haikel, Mossad Megahed, Mohamed Hassan

School of Medicine Faculty Publications

Immunotherapy, particularly that based on blocking checkpoint proteins in many tumors, including melanoma, Merkel cell carcinoma, non-small cell lung cancer (NSCLC), triple-negative breast (TNB cancer), renal cancer, and gastrointestinal and endometrial neoplasms, is a therapeutic alternative to chemotherapy. Immune checkpoint inhibitor (ICI)-based therapies have the potential to target different pathways leading to the destruction of cancer cells. Although ICIs are an effective treatment strategy for patients with highly immune-infiltrated cancers, the development of different adverse effects including cutaneous adverse effects during and after the treatment with ICIs is common. ICI-associated cutaneous adverse effects include mostly inflammatory and bullous dermatoses, as …

Interactions Of The Sars-Cov-2 Viral Genome 3’-Untranslated Region With Viral And Host Rnas, Caleb Frye, Mihaela Rita Mihailescu

Electronic Theses and Dissertations

This dissertation focuses on the characterization of RNA-RNA interactions within the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome and with host microRNAs. As the causative agent of coronavirus disease 2019 (COVID-19), SARS-CoV-2 has evolved rapidly since its appearance. This has warranted prompt characterization of the virus particularly of its single stranded RNA (ssRNA) genome. By using a combination of bioinformatics, biophysics, and/or biological assays, we analyzed the SARS-CoV-2 viral genomic RNA and uncovered interactions of genomic RNA with host RNAs, highlighting an underutilized method of targeting RNA viruses. We showed here that the conserved elements in the viral genomic …

Ccr5-Ligand Decorated Rilpivirine Lipid-Based Nanoparticles For Sustained Antiretroviral Responses, Milankumar Patel

Theses & Dissertations

Antiretroviral therapy (ART) is the standard remedy to improve the health-related quality of life of people living with human immunodeficiency virus (HIV). However, limited access to the viral reservoir has significantly hindered its effectiveness in fully eradicating HIV. Therefore, to improve HIV therapy, here we propose a C-C chemokine receptor type 5 (CCR5)-targeted theranostic lipid Based Nanoparticles (LBNPs) to noninvasively track and specifically deliver the antiretroviral drugs (ARVs) to the viral reservoir. A multi-modular radioactive nanoprobe was synthesized and co-encapsulated with rilpivirine (RPV, an ARV) into the LBNP to achieve a theranostic LBNP that can be tracked by positron emission …

Comparing Multivalent Cross-Linked Sodium Alginate/ Montmorillonite Beads Containing Curcumin Or Cayenne Pepper As Drug Carriers And Their Antimicrobial Resistance, Shionainn Traynor, Shubham Sharma

SURE Journal: Science Undergraduate Research Experience Journal

The aim of the following work was to investigate and compare curcumin and cayenne pepper in microbeads composed of sodium alginate (SA) crosslinked with montmorillonite (MMT) to act as drug carriers and their antimicrobial resistance. The microbeads were prepared through ion-exchange in multivalent solutions of CaCl₂, MgCl₂ and AlCl₃. The microbeads were characterized by Scanning Electron Microscopy (SEM), Energy Dispersive X-ray analysis (EDX) and the time required for intercalation of curcumin and cayenne pepper with MMT. Simulated intestinal fluid (pH 7.3) and gastric fluid (pH 1.2) at 37°C were used for comparison in swelling studies. …

Mathematical Modelling Of Disease Outbreak, Favour Christian, Matthew Molloy

SURE Journal: Science Undergraduate Research Experience Journal

Establishing a model framework for more research necessitates a thorough understanding of the causes, distribution, prevalence, and evolution of infectious illnesses. The main mathematical concept used in this modelling simulation is ordinary differential equations (ODEs). The purpose of this study was to investigate the significance of the many criteria linked to a zombie virus spread. The zombie framework provides an accessible and relatively simple representation of the nature of infectious disease spread, allowing for tractable assumptions and the development of more complex situations.

The models are designed around a zombie outbreak in which the zombie virus is spread through a …

Editorial - Sure Journal Vol 6, Anne M. Friel, Eva Campion, Sinead Loughran

SURE Journal: Science Undergraduate Research Experience Journal

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Tnf Prevents Establishment Of Anti-Tumor Immunity And Elucidates Toxicities Following Myxoma Virus Based Oncolytic Virotherapy, Miriam Beatriz Valenzuela Cardenas

Biomedical Sciences ETDs

Tumor Necrosis Factor Alpha (TNF) can lead to tumor regression through its direct cytolytic activity, yet it has also been implicated to facilitate tumor progression. This scenario complicates the efficacy and applicability of TNF based therapeutics as treatment for malignancies. In the context of oncolytic virotherapy (OV) which uses replicating viruses to treat tumors and acts by triggering production of pro-inflammatory cytokines, exploring such mechanisms is vital. Here we show that a Myxoma based oncolytic virus (vPD1/IL12) can induce large amounts TNF. The presence of TNF in the context of vPD1/IL12 plays a detrimental role both for tumor regression by …

Testing Vivo-Morpholino Mediated Gene Knockdown Of Stat6, Spi1b, And Hnf4Α In Adult Threespine Stickleback, Stella Dipippo

Honors Scholar Theses

The fibrotic immune response to the cestode parasite, Schistocephalus solidus, varies among threespine stickleback populations. Fibrosis suppresses parasite growth but has costly effects on the fish. Previous genomic studies in stickleback have suggested potential roles of Spi1b, STAT6, and HNF4α in modulating fibrosis severity, but there is presently no evidence for this in-vivo. We used antisense vivo-morpholino oligonucleotides (MOs) to attempt to knockdown the expression of each gene in the liver, spleen, and intestine of adult stickleback. Vivo-MOs have been proven effective in other species of teleost fish, as well as in mice and humans, but …

A Kid's Guide To Infectious Disease, Abby Carroll

Honors Theses

A Kid’s Guide to Infectious Disease is an educational illustrated book intended for young pediatric patients, ages three to five. This project was inspired by my personal interests, involvement at the University of Mississippi, and experience as a medical assistant. Over the past couple of years, I have had the opportunity to work as a medical assistant, interacting with many pediatric patients and their families at HealthPointe Primary Care. As a pre-physician assistant student studying biology, I was inspired to create a resource for these kids by both my classes at the University of Mississippi and my passion for pediatric …

Proteolytic Manipulation Of Neutrophil Responses And The Efferocytic Synapse By Porphyromonas Gingivalis., Kelley N. Cooper

Electronic Theses and Dissertations

Porphyromonas gingivalis (Pg) is etiologically associated with chronic periodontitis, a highly prevalent chronic inflammatory disease characterized by the destruction of hard and soft tissues of the periodontium. Pg is adapted to live in the human oral subgingival niche, a hostile environment dominated by excessive numbers of activated neutrophils and antimicrobial mediators. Its survival is contingent upon prompt and effective inactivation of neutrophil effector functions. In this dissertation, I uncover a novel pathogenic mechanism employed by Pg that disarms the antimicrobial capacity of live neutrophils and simultaneously sequesters them within macrophages. Mechanistically, RgpB, a cysteine protease produced by Pg …

Differential Responses Of Human Neutrophils To Legionella Species., Hannah E. Hanford

Electronic Theses and Dissertations

Legionella species are Gram-negative facultative intracellular bacterial pathogens commonly found in freshwater or soil environments where they survive and replicate within their natural protozoan hosts. Humans serve as an accidental host for Legionella species after inhalation of contaminated aerosolized water droplets or soil particles enabling the bacteria to enter the lungs, infect alveolar macrophages, and result in severe pneumonia. Evasion of degradation and proliferation within alveolar macrophages by Legionella species and manifestation of “Legionnaires’ disease” is dependent on the Dot/Icm type IV secretion system (T4SS). The T4SS apparatus is a needle-like channel for translocation of over ~350 effector proteins, depending …

Soybean Cyst Nematode (Heterodera Glycines Ichinohe) Virulence Assay Against Resistance Sources In Nebraska, Pratibha Karki

Department of Plant Pathology: Dissertations, Theses, and Student Research

Soybean cyst nematode (SCN, Heterodera glycines Ichinohe), one of the major yield-limiting pathogens of soybean, is currently found in 60 counties of Nebraska that produce more than 90% of the state’s soybean. Often, yield loss occurs without any above-ground symptoms, which makes it difficult to manage. The primary management option is the use of SCN-resistant varieties. Several soybean plant introductions serve as resistance sources against SCN. Unfortunately, the single source, PI 88788, is used in approximately 90% of resistant varieties and its prolonged use has increased the virulence status of SCN in the U.S. A study was conducted to assess …

The Informal, Non-Prescribed Use Of Antiretroviral Medications For Prep Among A National Us-Based Sample Of Gay, Bisexual, And Other Men Who Have Sex With Men: A Cross-Sectional Study, Mance E. Buttram, Matthew S. Ellis, Krishen D. Samuel, Matthew Hayhurst

Health, Human Performance and Recreation Faculty Publications and Presentations

This brief report presents findings on informal, non-prescribed PrEP use among an online sample of gay, bisexual and other men who have sex with men (n = 196). Mean age was 33.4. Participants were Hispanic (13.3%), African American (15.8%), white (63.8%), and other race/ethnicity (6.6%). Informal PrEP users (11%) more frequently reported past year sexually transmitted infections (p < 0.001), group sex (p < 0.001), sex in public (p < 0.01), transactional sex (p < 0.001), ever receiving a formal PrEP prescription (p < 0.05), and ease of finding diverted HIV medications on gay dating/sex apps (p < 0.05). Formal PrEP uptake should be encouraged to mitigate potential negative consequences of informal use.

Lack Of Inflammatory Response In Mouse Embryonic Cells To Listeria Infection, Damilola Oyebode

Master's Theses

Approximately 1 in 5 pregnancies in the United States results in miscarriage, with a significant percentage of these losses attributed to failed implantation due to immunological challenges encountered by the early embryo. Recent research has shown that key cell types within mouse blastocysts, including embryonic stem cells (ESCs) and trophoblast stem cells (TSCs), exhibit remarkable resilience against the cytotoxic effects associated with viral infections and embryotoxic cytokines, such as TNFα and IFNγ, both of which are known to hinder blastocyst development. However, the immune properties of the preimplantation stage embryo, specifically the blastocyst, remain poorly understood. Using mouse cell model, …

Timigp: A Computational Framework To Determine The Tumor Immune Microenvironment Associated With Prognosis And Immunotherapy Response, Chenyang Li

Dissertations and Theses (Open Access)

Accumulating evidence has suggested that the tumor immune microenvironment (TIME) drastically impacts cancer patients’ clinical outcomes, including prognosis and immunotherapy response. However, understanding TIME remains challenging due to its complexity and heterogeneity. In this dissertation, we introduce TimiGP (Tumor Immune Microenvironment Illustration based on Gene Pairs), a computational framework designed to address this challenge. Leveraging single-cell RNA-seq (scRNA-seq) and bulk gene expression data alongside clinical information, TimiGP constructs a cell-cell interaction network that elucidates the relationship between immune cell function and relevant clinical outcomes, such as prognosis and treatment response. With immunological insights, these cell-cell interactions also facilitate the development …

The Role Of Lifr Signaling In Innate Immunity, Laura Kahn Serrudo

Dissertations and Theses (Open Access)

The localized signals that bone marrow (BM) hematopoietic stem cells (HSCs) and immune cells receive are critical in regulating their responses in the steady state and inflammation. Monocytes are an abundant and key population in the innate immune response that originates in the BM, and they circulate to monitor the periphery. Monocytes are composed of many subsets that have essential and specific functions, including swift egress from the BM, production of pro-inflammatory cytokines, and differentiation into monocyte-derived dendritic cells (MoDCs), which are required for efficient pathogen eradication.

Here, we uncovered LIFR (leukemia inhibitory factor receptor) restrains low-grade chronic inflammation in …

Oncolytic Viruses Enhance Long-Term Nk Cell Anti-Tumor Cytotoxicity Through Ap-1 And Irf Pathway Activation, Xin Ru Jiang

Dissertations and Theses (Open Access)

Natural killer (NK) cell therapeutics have emerged as a promising strategy in adoptive cellular therapy. While genetic modifications of NK cells can enhance their antitumor activity, modulating the tumor to augment NK cell recognition and function remains underexplored. In this study, we investigated the combination of NK cells with oncolytic viruses to treat solid tumors, specifically pancreatic ductal adenocarcinoma and glioblastoma. We demonstrated that infecting tumor cells with the oncolytic adenovirus Delta-24-RGD significantly increases their susceptibility to NK cell cytotoxicity, driven by a hyperactivated NK cell phenotype characterized by elevated expression of activating receptors and cytotoxicity markers. In a patient-derived …

Local Or Systemic Antibody-Targeted Sting Activation Drives Pro- Inflammatory Stromal Metabolic Changes And Downregulates C-Myc Oncoprotein, Akash Boda

Dissertations and Theses (Open Access)

The past decade has witnessed remarkable advances in the field of cancer immunotherapy. Immune checkpoint blockade (ICB) has emerged as a cornerstone, achieving long-lasting tumor regression in several types of cancer. However, its effectiveness is often limited, particularly in certain tumor types. Immunologically "cold" tumors, such as pancreatic ductal adenocarcinoma (PDAC), remain clinically unresponsive to ICB, presenting a significant challenge in oncology. Amidst these challenges, the stimulation of the STING pathway via small molecule synthetic agonists has surfaced as a promising strategy. Acting as an in-situ vaccine, STING activation has the potential to transform the immune landscape of cold tumors …

The Role Of Ganglioside Gd2 And Gd3 Synthase (St8sia1) In The Regulation Of Immune Suppression In Breast Cancer, Bolutyfe Oderinde

Dissertations and Theses (Open Access)

Gangliosides are acidic glycosphingolipids involved in cell adhesion, proliferation, and modulation of signal transduction pathways. It has been reported that tumor-shed gangliosides influence the activity of immune cells including macrophages, NK cells, and T cells. GD3 synthase (GD3S) is the key enzyme that regulates the biosynthesis of the b and c series gangliosides, particularly GD3 and GD2, and studies have shown that GD3S is upregulated in most tumors and plays a role in tumor progression. Similarly, we have previously found GD3S to be significantly upregulated in GD2+ breast cancer stem cells (BCSC) compared to GD2- cells, and the knockdown of …

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) …

Dissecting Metabolic Landscape Of Alveolar Macrophage, Sunayana Malla

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

The highly plastic nature of alveolar macrophage (AM) plays a crucial role in the defense against inhaled particulates and pathogens in the lungs. Depending on the signal, AM acquires either the classically activated M1 phenotype or the alternatively activated M2 phenotype. In this study, we investigate the metabolic shift in the activated phases of AM (M1 and M2 phases) by reconstructing context specific genome-scale metabolic (GSM) models. Metabolic pathways such as pyruvate metabolism, arachidonic acid metabolism, chondroitin/heparan sulfate biosynthesis, and heparan sulfate degradation are found to be important driving forces in the development of the M1/M2 phenotypes. Additionally, we formulated …

Finding Them Before They Find Us: Solving The Emerging Infectious Disease Crisis, Daniel R. Brooks

MANTER: Journal of Parasite Biodiversity

The human population grows daily, it’s on the move, and it’s carving a deep technological footprint on our planet. We alter landscapes and perturb ecosystems, inserting ourselves and other species into novel regions of the world, leading to potentially irreversible changes in the biosphere. This is not news. More than 75 years ago, Charles Elton, one of the founders of modern ecology, wrote, “We must make no mistake; we are seeing one of the greatest historical convulsions in the world’s fauna and flora.” We are also in the midst of a public health and epidemiological crisis. Climate change alters movements …

Association Of Acute Rejection And De Novo Renal Cell Carcinoma In Kidney Transplant Patients: An Optn Data Analysis, Molly Casey, Emmalie Yanacek, Hitesh Kaul, John Knorr, Kamran Khanmoradi, Afshin Parsikia, Nikolaos Chandolias, Kevin Zarrabi, Radi Zaki

Einstein Health Papers

Background: Kidney Transplant Recipients (KTRs) are at risk of renal cell carcinoma (RCC). The risk of RCC in KTRs is approximated to be 5–10 times higher compared with the general population. A relation between kidney rejection and renal malignancy has been described and relates to the effect of immunosuppression at the genomic level. We decided to investigate any suggestive clinical evidence of this in the OPTN database. Methods: KTRs with de novo RCC between July 2004 and June 2022 were identified. Demographics, baseline characteristics, virology, and immunology data were compared between patients with and without RCC. Our follow-up period was …

Multiple Factors Regulate The Expression Of Sufcdsub In Streptococcus Mutans, Kassapa Ellepola, Lauren C. Guillot, Bradley Comeaux, Yiran Han, Jessica K. Kajfasz, Jacob P. Bitoun, Grace Spatafora, Jose A. Lemos, Zezhang T. Wen

School of Dentistry Faculty Publications

Introduction: The sufCDSUB gene cluster, encoding the sole iron-sulfur (Fe-S) cluster assembly system in S. mutans, was recently shown to be up-regulated in response to oxidative stressors and Fe limitation. Methods: In this study, luciferase reporter fusion assays, electrophoretic gel mobility shift assays (EMSA) and in vitro transcription assays (IVT) were used to dissect the cis- and trans-acting factors that regulate the expression of sufCDSUB. Results and discussion: Results showed deletion of perR, for the only Fur-family transcriptional regulator in S. mutans, resulted in > 5-fold increases in luciferase activity under the control of the sufCDSUB promoter (P < 0.01), as compared to the parent strain, UA159 when the reporter strains were grown in medium with no supplemental iron. Site-directed mutagenesis of a PerR-box in the promoter region led to elevation of the reporter activity by >1.6-fold (P < 0.01). In an EMSA, recombinant PerR (rPerR) was shown to bind to the cognate sufCDSUB promoter leading to mobility retardation. On the other hand, the reporter activity was increased by > 84-fold …

Pathway-Based Polygenic Risk Score Analysis Of Brain Glial Indicates Cell-Type-Specific Roles In Alzheimer's Disease, Tyrell Pratt, Alice Lee, Jennifer Zheng, Faria Tavacoli, Hayley Ho, Tingwei Liu, Jingchun Chen

Undergraduate Research Symposium Posters

Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by progressive cognitive decline and extensive brain pathology, including amyloid plaques, neurofibrillary tangles, and neuroinflammation. This study aims to identify any glial cell type-specific pathways associated with AD.

Methods: We first investigated the correlation between AD and the genetic risk of glia-specific pathways using pathway-based polygenic risk score (PRS) with PRSet software in the discovery data (ADc1234ADA) adjusted by the top two principal components (PC1, PC2) (Model 1), followed by additional adjustment with sex, age, and APOE ε4 count in Model 2. Further PRSet analyses were replicated in independent data …

Glial-Specific Genes Are Strongly Associated With Alzheimer's Disease By Gene-Based Polygenic Risk Score Analysis, Jennifer Zheng, Faria Tavacoli, Tyrell Pratt, Alice Lee, Tingwei Liu, Jingchun Chen

Undergraduate Research Symposium Posters

Methods: Gene-based PRSs were constructed in AD cases and controls within each gene of the glial cells, according to the GWAS summary statistics of European ancestry. In detail, gene-based PRSs were first calculated for each glial cell type-specific gene for AD cases and controls in the discovery dataset (ADc1234ADA) using PRSet software. A meta-analysis with a fixed model was performed when the signal in both datasets was in the same direction. Bonferroni corrections for multiple testing (at α = .05) were used to determine significance within each of the three glial groups. Forest plots were used to visualize the results …

Effect Of Macronutrients On A Rat Model Of Clostridioides Difficile Infection, Stephanie Yang, Maria Niamba, Rose Jiang, Ashton Wippel, Efren Heredia, Liliko Watanabe, Katrina Valadez, Erica Bacab, Ernesto Abel-Santos

Undergraduate Research Symposium Posters

Clostridioides difficile (C. diff) is an anaerobic, spore forming, gram-positive bacteria. C. diff is the causative agent of C. difficile infections (CDIs) and is recognized as the leading cause of nosocomial infective diarrhea worldwide. CDI is associated with the use of antibiotics that alter the gut microbiome and C. diff resides in the large intestine where onset of the disease then occurs. Having observed the impacts of CDI on mice models, the Abel-Santos lab now shifts to observing this infectious disease in rat models. Establishing the infectious dosage at 109 spores, this study aims to identify the correlation between diet …