Immunology and Infectious Disease Commons^™

Exploring The Role Of Host Immune Responses And Bacterial Sensory Pathways In The Development Of Treponema Denticola-Mediated Periodontal Disease, Annie N. Hinson

Theses and Dissertations

Periodontitis is a chronic inflammatory disease driven by dysbiotic microbial communities and maladaptive host responses. Treponema denticola, a spirochete pathobiont, is strongly associated with disease severity. However, the molecular mechanisms underlying its interaction with host tissues and regulation of virulence remain incompletely understood. This work examines both the epithelial immune responses and bacterial transduction systems that shape T. denticola pathogenesis. Transcriptomic analysis of gingival keratinocytes revealed IL-36γ as the most highly induced cytokine following infection with T. denticola. Functional studies demonstrated that IL-36γ induction occurs in a dose- and time-dependent manner through TLR2/6 signaling, requiring the NF-κB, PI3K/Akt, and …

Functional Analysis Of Ligand Binding Domain 2 Of Outer Surface Protein C Of Borreliella Burgdorferi, Gavin Z. Chambers

Theses and Dissertations

Lyme disease, caused by the spirochete Borreliella burgdorferi, is the most common vector-borne infection in North America. A critical determinant of early mammalian infection is outer surface protein C (OspC), a highly variable lipoprotein that is indispensable for spirochete survival but whose precise function remains unresolved. OspC has been proposed to mediate diverse roles, including complement evasion, adhesion, tissue dissemination, and antiphagocytic activity, supporting the view that it is a multifunctional virulence factor. Structural studies have identified two putative ligand-binding domains (LBD1 and LBD2), with LBD2 forming a solvent-exposed crown at the membrane-distal end of the OspC dimer.

To …

Bacteria-Engineered Vesicles For Cancer Immunotherapy: From Immunomodulation In Vitro To Anti-Tumor Effects In Melanoma Models, Lan Li

Theses and Dissertations--Chemistry

Bacterial vesicles hold immense potential in various biomedical fields. Among these, outer membrane vesicles (OMVs) produced by Gram-negative bacteria are the most extensively studied. While the exact mechanism of OMV production remains unclear, numerous environmental factors have been shown to influence both their yield and composition. In this study, we investigated the effect of three different antimicrobial families on OMV production by E. coli. Interestingly, antimicrobials within the same family did not provide the same effects on OMV yield, suggesting that OMV production may not directly correlate with the antimicrobial mechanism of action. OMVs have demonstrated tumor-inhibitory activity in multiple …

Npr1 As A Temperature-Sensitive Regulator Of Pipecolic Acid-Mediated Plant Systemic Immunity, Spencer Tout

Theses and Dissertations (Comprehensive)

Healthy plant development requires balancing both abiotic (e.g. climate) and biotic (e.g. pathogen) challenges, which intercept important signaling pathways in plants. For example, climate change-associated elevated temperature can negatively modulate various aspects of plant immunity, including the production of central immune signals salicylic acid (SA) and N-hydroxypipecolic acid (NHP). Since SA and NHP signaling both require the master immune co-activator protein NON-EXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1), it is important to investigate NPR1 as a potentially temperature-regulated molecular hub. Although the NPR1 gene is not transcriptionally downregulated at elevated temperatures (28° C vs. 23° C), little is known about …

Antibody-Induced Multicellular Behaviors Of Salmonella Typhimurium, Samantha K. Lindberg

Electronic Theses & Dissertations (2024 - present)

Salmonella enterica is a globally distributed bacterial pathogen that is commonly acquired through consumption of contaminated food and water. The enterica subspecies includes over 1500 unique subvariants, or serovars, that are classified by antigen presentation. Due to its global environmental prevalence, broad host range, and increasing pathogenicity, serovar Typhimurium is of particular concern for human and animal health, as well as food safety. Once in the gastrointestinal tract, Salmonella Typhimurium (STm) exploits host immune mechanisms, implements an arsenal of virulence factors, and outcompetes the microbiota to invade the intestinal epithelium. While STm infections are generally self-limiting and relatively mild, emerging …

Hsa-Mir-214-3p Inhibits Breast Cancer Cell Growth And Improves The Tumor Immune Microenvironment By Downregulating B7h3, Yan Lu, Kang Wang, Yuanhong Peng, Meng Chen, Lin Zhong, Luji Huang, F U Cheng, Xindan Sheng, Xin Yang, Manzhao Ouyang, George A Calin, Zhiwei He

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors play an important role in the treatment of solid tumors, but the currently used immune checkpoint inhibitors targeting programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 (CTLA-4) show limited clinical efficacy in many breast cancers. B7H3 has been widely reported as an immunosuppressive molecule, but its immunological function in breast cancer patients remains unclear.

METHODS: We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program (TCGA) and the Gene Expression Omnibus (GEO) databases. MicroRNAs were selected using the TarBase, miRTarBase, and miRBase databases. …

Engineering Extracellular Vesicles (Evs) To Combat Infection And Inflammation In Cystic Fibrosis, Sharanya Sarkar

Dartmouth College Ph.D Dissertations

Cystic Fibrosis (CF) is a multisystemic genetic disorder caused by mutations in the CFTR gene, resulting in chronic pulmonary infections, hyperinflammation, and progressive lung damage. Among the pathogens that colonize CF lungs, Pseudomonas aeruginosa (P. aeruginosa) is predominant, infecting over 50% of adults with CF and developing antibiotic resistance over time. Current modulator therapies fail to address persistent bacterial infections, chronic inflammation, or irreversible lung damage, underscoring the need for novel therapeutic strategies. In our previous in vitro studies, we demonstrated that extracellular vesicles (EVs) secreted by primary Human Bronchial Epithelial Cells (HBECs) inhibit P. aeruginosa growth by reducing the …

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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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 …

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 …

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 …