Immunology and Infectious Disease Commons^™

One Year Follow Up Of A Cross-Sectional Study Of Hookworm Infection And Response To Deworming In Beposo, Ghana, Taylor Clarkson

Capstone Experience: Master of Public Health

Hookworms are soil-transmitted helminths that infect over 500 million people worldwide, primarily those in low-income countries. Infection with hookworm can cause anemia, malnutrition, and stunted physical and cognitive development. Deworming campaigns have attempted to combat hookworm infections in endemic areas for decades. However, there is growing variability in the effectiveness of deworming drugs, and post-treatment reinfections are abundant. There are significant gaps in our understanding of critical host-parasite factors that mediate hookworm infection, reinfection, and response to deworming treatment in endemic communities. A five-year prospective study was undertaken to better understand drivers of hookworm infection in rural Ghana and thus …

The Role Of Oncomodulin In The Central Nervous System Inflammation, Evan Paltjon

Honors Theses

Acoustic overexposure in mice leads to an excess of calcium influx in outer hair cells (OHCs) and causes permanent hearing loss due to death of OHCs. Oncomodulin is a parvalbumin calcium buffering protein located in OHCs of the cochlea. Early pilot studies indicate that genetic deletion of OCM results in immune-related pathology throughout the cochlea. Why and how this occurs is unknown. Studies in wild type (WT) and OCM knockout (KO) mice demonstrate greater numbers of immune cells are associated with noise exposure in an OCM knockout than in WT. Expression of toll-like receptor 4 (TLR4) leads to the recruitment …

The Role Of B Cell Activation State And Sex In Aryl Hydrocarbon Receptor Mediated Induction Of Chemokine Receptor 9 And Alpha4beta7 Expression In Vitro, Logan Bauerle

Master's Theses

Defense of mucosal tissues from microbial infection and allergy is reliant on continual production of antibodies. The aryl hydrocarbon receptor (AhR) is known to regulate B cell development and is associated with suppression of systemic humoral immunity. Recent attention has been paid to the role of the AhR in altering expression of cell adhesion molecules (CAMs). B cells express CAMs and chemokine receptors to migrate around the body for localized secretion of antibodies. AhR agonists promote B cell migration to the small intestine through upregulation of chemokine receptor 9 (CCR9) and integrin α₄β₇. Both the AhR …

The Association Between Aerobic Exercise And Changes In Hdl Quality Induced By Egg Consumption – A Post-Hoc Analysis Of A Randomized, Controlled, Crossover Dietary Intervention Study, Rachael Woodruff, Catherine J. Andersen

Honors Scholar Theses

Abstract

Objective: Daily intake of whole eggs and aerobic exercise have independently been shown to increase high-density lipoprotein cholesterol (HDL-C) and measures of HDL function, suggesting cardioprotective effects of these lifestyle interventions. However, it is unknown whether exercise volume can synergistically or differentially impact diet responses and egg effects on HDL. Therefore, we evaluated whether exercise volume was associated with distinct effects of consuming different egg-based diets on measures of HDL size, function, and composition.

Methods: Twenty-six healthy men and women completed a 16-week randomized, controlled, crossover intervention study which aimed to investigate the effects of egg-free, egg-white, and whole-egg …

Pipecolic Acid And Novel Insights Into Cerebral Malaria, Akua E. Mensah

Theses and Dissertations

Cerebral malaria (CM), a severe manifestation of Plasmodium infection, prompts our investigation into the nuanced role of pipecolic acid in its pathophysiology. To unravel the molecular intricacies, we conducted in vitro lysine labeling techniques of mice infected with P. berghei ANKA parasites, and human P. falciparum grown in vitro, aiming to discern the impact of Plasmodium on pipecolic acid production. Previous observations indicated an elevation in pipecolic acid levels correlating with neurological decline in children with CM. In our study, confirming elevated pipecolic acid presence in the plasma and brain tissues of CM patients and the animal model of CM, …

Investigating Outcomes Of Emerging Treatments For Cerebral Palsy, Hannah Halt

University Honors College

Cerebral palsy presents a complex neurological challenge affecting movement and posture, with significant implications for individuals' quality of life. This essay provides a thorough examination of cerebral palsy, covering its prevalence, types, and associated health conditions. It explores current treatment modalities, including constraint-induced therapy, gaitfocused physical therapy, and cell-based therapies, highlighting their effectiveness and cost considerations. Ethical dilemmas in stem cell research for cerebral palsy are being discussed, alongside ongoing clinical trials and their potential impact. Through a multidisciplinary approach, this essay sheds light on the evolving landscape of cerebral palsy treatment, emphasizing the importance of early detection and intervention …

Mismatch Repair Deficient Neoantigen And Associated Circulating T-Cell Receptor Repertoires In Lynch Syndrome, Ana Bolivar

Dissertations and Theses (Open Access)

Lynch Syndrome (LS) is the most common inherited colorectal cancer (CRC) syndrome. It constitutes the perfect model to understand DNA mismatch repair deficient (MMRd) carcinogenesis, which underlies 15% of early-stage CRC. LS patients develop MMRd tumors with high loads of shared neoantigens (neoAgs), which are recognized by the immune system. Previous research has concentrated on discovering neoAgs and their potential as targets for vaccines in LS patients. However, these studies have primarily identified shared neoAgs from cancers, lacking detailed information on targetable neoAgs present in precancerous lesions. Understanding this landscape of pre-cancer derived neoAgs is crucial for intercepting cancer development …

Plant Model Of Α-Synucleinopathy: Expression Of Α-Synuclein A53t Variant In Hairy Root Cultures Leads To Proteostatic Stress And Dysregulation Of Iron Metabolism, Jasmina Kurepa, Kristen A. Bruce, Greg A. Gerhardt, Jan A. Smalle

Neurology Faculty Publications

Synucleinopathies, typified by Parkinson’s disease (PD), entail the accumulation of α- synuclein (αSyn) aggregates in nerve cells. Various αSyn mutants, including the αSyn A53T variant linked to early-onset PD, increase the propensity for αSyn aggregate formation. In addition to disrupting protein homeostasis and inducing proteostatic stress, the aggregation of αSyn in PD is associated with an imbalance in iron metabolism, which increases the generation of reactive oxygen species and causes oxidative stress. This study explored the impact of αSyn A53T expression in transgenic hairy roots of four medicinal plants (Lobelia cardinalis, Artemisia annua, Salvia miltiorrhiza, and Polygonum multiflorum). In all …

Inhibition Of Pro-Inflammatory Lipid Mediators By Yersinia Pestis., Amanda Brady

Electronic Theses and Dissertations

Yersinia pestis causes the human disease known as plague. A key manifestation of plague is a delayed inflammatory response. Because this delay in inflammation is required for virulence, I was interested in defining the molecular mechanisms used by Y. pestis to evade immune recognition. Eicosanoids are produced early during infection and necessary to initiate a rapid inflammatory response. Despite the importance of these lipids in mediating inflammation, the role of eicosanoids during plague has not been previously investigated. Using an intranasal mouse model infection, I determined the kinetics of eicosanoid synthesis during pneumonic plague. I further demonstrated that LTB_{4 …}

Oxidative Phosphorylation In Melanoma Brain Metastases: A Regulator Of The Tumor Immune Landscape, Renato A. Guerrieri

Dissertations and Theses (Open Access)

Previously, we demonstrated via RNA-sequencing analysis of murine intracranial melanoma tumors that pharmacologic inhibition of oxidative phosphorylation (OXPHOS) results in increased expression of genes consistent with activated anti-tumor immune responses. The central hypothesis of this dissertation is that OXPHOS plays a critical role in the pathogenesis and immune regulation of melanoma brain metastases (MBMs).

The functional significance of OXPHOS was assessed through genetic inhibition, involving knockout (KO) of key regulatory genes such as Ppargc1a (PGC1a) and Ndfus4 (NDUFS4), a component of mitochondrial complex I. PGC1a KO in an RCAS-TVA mouse model of autochthonous lung and brain tumors developing from primary …

Mast Cells In Mammary Carcinoma, Alexandria M. Ashbaugh

Undergraduate Honors Theses

Breast cancer (BC) is an aggressive disease that takes the lives of thousands of women every year. Although knowledge and treatment of this disease have improved over the years, much is still to be discovered about BC. One area of expertise that we are currently trying to learn more information about is the mast cell (MC) and its role in BC growth and development. The MC is an immune system component discovered in tumors' extracellular matrix (ECM). As a tumor grows within body tissues, the tumor recruits the MC from surrounding connective tissues to the tumor, using signaling cytokines such …

Concepts In Animal Parasitology: Master Bibliography, Sue Ann Gardner

Concepts in Animal Parasitology

Master bibliography for the open educational resource/open access textbook Concepts in Animal Parasitology, Scott L. Gardner and Sue Ann Gardner, editors, published by Zea Books, Lincoln, Nebraska, United States, 2024. This includes the references from literature cited and suggested supplemental reading.

The Role Of Anti-Viral Immune Response On The Therapeutic Efficacy Of Oncolytic Virotherapy For High-Grade Gliomas, Dong Ho Shin Phd

Dissertations and Theses (Open Access)

Currently, there is no effective treatment for high-grade gliomas that are resistant to conventional treatments and immune checkpoint blockade therapies. Oncolytic viruses offer a new treatment modality by selectively replicating in cancer cells and inducing anti-tumor immunity. Among these viruses, the oncolytic adenovirus Delta-24-RGD has shown safety and efficacy in clinical trials for high-grade gliomas. Strategies to improve the efficacy of oncolytic virotherapy have aimed to heighten the immunogenicity of oncolytic viruses, either by incorporating immune-stimulating transgenes or by combining treatments with immune checkpoint blockades. However, such strategies may inadvertently trigger heightened immune responses to viral antigens, which may not …

Loss Of Ptdss1 In Tumor Cells Improves Anti-Pd-1 Therapy, Jielin Liu

Dissertations and Theses (Open Access)

PTDSS1 (Phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of PTDSS1 in tumor cells increased expression of IFNγ-regulated genes, including B2m, Cxcl9, Cxcl10, and Stat1. Loss of PTDSS1 in tumor cells also led to increased expression of MHC-I, which was associated with increased expression of cytolytic function related genes in CD8⁺ T cells and increased frequency of an iNOS⁺ myeloid subset. A gene signature derived from the iNOS⁺ myeloid …

Exploring The Role Of Il-1Β/Il-1r In The Pathogenesis Of K-Ras Mutant Lung Cancer, Avantika Krishna

Dissertations and Theses (Open Access)

As the leading cause of cancer-related deaths worldwide, the development of targeted therapeutics to treat lung cancer remains crucial. Non-small cell lung cancer (NSCLC), the most common histological subtype predominantly comprises lung adenocarcinoma with driver mutations in the K-ras oncogene (KM-LUAD). KM-LUAD progression partly occurs through activation of the NF-κB pathway initiating an inflammatory response and creating a pro-tumor microenvironment. Notably, the pro-inflammatory cytokine IL-1β a potent activator and product of the NF-κB pathway is elevated in the lungs and sera of KM-LUAD patients. We have shown that IL-1β blockade promotes an anti-tumor immune phenotype in a mouse model of …

Rna Knockdown Of The Immune Checkpoint Vista Promotes Tumor Regression, Brittany Morrow, Brittany A. Morrow

Dissertations and Theses (Open Access)

Blockade of negative immune regulators for example CTLA-4, and PD-1/PD-L1 has proven to be a clinically effective strategy to enhance tumor specific immune responses. Recently discovered novel immunoglobulin superfamily ligand V-domain Ig suppressor of T-cell Activation (VISTA) is a new target for immunotherapy. VISTA expression is specifically upregulated on tumor infiltrating myeloid cells such as dendritic cells (DCs), tumor associated macrophages (TAMs) and myeloid derived suppressor cells (MDSCs). In addition, VISTA expression is increased on tumor-infiltrating regulatory T cells (Tregs) compared to those in the periphery. VISTA has been shown to suppress effector T cells through multiple mechanisms, primarily by …

Importance Of Specific Nk Cell Subsets For Antitumor Immunity In Hpv+ Cancers, Madison O'Hara

Dissertations and Theses (Open Access)

High-risk type human papillomaviruses (HPV) are associated with genital and oral cancers, and the incidence of HPV+ head and neck squamous cell cancers is fast increasing worldwide. Survival rates for patients with locally advanced disease are poor and variable after standard of care (SOC) treatment. Identifying the antitumor host immune mediators important for treatment response and designing strategies to promote them are essential for improving clinical outcome. The natural killer (NK) cells are a critical component for antitumor innate effector immunity. Among the multitude of activation and inhibitory receptors on immune cells, HLA-DR is recognized as an important activation marker …

Regulation Of Cd4 T Cell Functions By Ncrna-Mediated Signaling Pathways During Chronic Viral Infections, Lam Nguyen

Electronic Theses and Dissertations

CD4 T cell homeostasis and competency are critical for the effectiveness of antiviral immunity. However, CD4 T cells derived from people living with HIV (PLWH) and individuals with chronic HCV infection often exhibit an inflammaging phenotype, evidenced by persistent inflammation, immune activation, exhaustion, senescence, and cellular apoptosis. Despite intensive investigations, the molecular mechanisms underlying CD4 T cell dysfunction in antiretroviral therapy (ART)-controlled PLWH and HCV-infected patients remain poorly understood. By investigating the roles of non-coding (nc)RNA transcripts in regulating the functions of CD4 T cells derived from PLWH and HCV-infected patients, we demonstrated that long non-coding (lnc)RNA - growth arrest-specific …

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 …

Adding Parasite Resistance To A Hair Sheep Breeding Objective, Robert M. Forbes

Department of Animal Science: Dissertations, Theses, and Student Research

The United States Hair Sheep Index was designed to increase total weight of lamb weaned per ewe lambing (TW) using estimated breeding values (EBV) for direct (DWWT) and maternal (MWWT) weaning weight, and number of lambs born (NLB) and weaned (NLW), as selection criteria. Producers are interested in adding post-weaning fecal egg count EBV (PFEC), an indicator of parasite resistance, to the index to achieve genetic change in both TW and PFEC.

First, the effects of adding PFEC alongside TW to the breeding objective of indexes that used either phenotypes or EBV as selection criteria were studied. Since MWWT …

High-Grade Pleomorphic Sarcomas Treated With Immune Checkpoint Blockade: The Md Anderson Cancer Center Experience, Lewis F Nasr, Marianne Zoghbi, Rossana Lazcano, Michael Nakazawa, Andrew J Bishop, Ahsan Farooqi, Devarati Mitra, Beverly Ashleigh Guadagnolo, Robert Benjamin, Shreyaskumar Patel, Vinod Ravi, Dejka M Araujo, Andrew Livingston, Maria A Zarzour, Anthony P Conley, Ravin Ratan, Neeta Somaiah, Alexander J Lazar, Christina Roland, Emily Z Keung, Elise F Nassif Haddad

Faculty, Staff and Student Publications

BACKGROUND: Undifferentiated pleomorphic sarcomas (UPSs) are amongst the most common subtypes of soft-tissue sarcomas. Few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and other high-grade pleomorphic STS patients are available.

PURPOSE: The purpose of our study is to describe the efficacy and toxicity of ICB in patients with advanced UPSs and other high-grade pleomorphic sarcomas treated at our institution.

METHODS: This is a retrospective, observational study of all patients with metastatic high-grade pleomorphic sarcomas treated with FDA-approved ICB at MD Anderson Cancer Center between 1 January 2015 and 1 January 2023. Patients included in …

Neoadjuvant Chemoimmunotherapy For Nsclc: A Systematic Review And Meta-Analysis, Mark Sorin, Connor Prosty, Louis Ghaleb, Kathy Nie, Khaled Katergi, Muhammad H Shahzad, Laurie-Rose Dubé, Aline Atallah, Anikka Swaby, Matthew Dankner, Trafford Crump, Logan A Walsh, Pierre O Fiset, Boris Sepesi, Patrick M Forde, Tina Cascone, Mariano Provencio, Jonathan D Spicer

Faculty, Staff and Student Publications

IMPORTANCE: To date, no meta-analyses have comprehensively assessed the association of neoadjuvant chemoimmunotherapy with clinical outcomes in non-small cell lung cancer (NSCLC) in randomized and nonrandomized settings. In addition, there exists controversy concerning the efficacy of neoadjuvant chemoimmunotherapy for patients with NSCLC with programmed cell death 1 ligand 1 (PD-L1) levels less than 1%.

OBJECTIVE: To compare neoadjuvant chemoimmunotherapy with chemotherapy by adverse events and surgical, pathological, and efficacy outcomes using recently published randomized clinical trials and nonrandomized trials.

DATA SOURCES: MEDLINE and Embase were systematically searched from January 1, 2013, to October 25, 2023, for all clinical trials of …

Hierarchal Single-Cell Lineage Tracing Reveals Differential Fate Commitment Of Cd8 T-Cell Clones In Response To Acute Infection., Leena Abdullah

Dartmouth College Ph.D Dissertations

Generating balanced populations of CD8 effector and memory T cells is necessary for immediate and durable immunity to infections and cancer. Yet, a definitive understanding of CD8 differentiation remains unclear. Here we used CARLIN, a processive lineage recording mouse model with single-cell RNA-seq and TCR-seq to track endogenous antigen-specific CD8 T cells during acute viral infection.

Transcriptional profiling of antigen-specific T cells at the peak of the effector response to Vesicular stomatitis virus uncovered a diverse repertoire of expanded antigen-specific T-cell clones represented by seven transcriptional states. TCR enrichment analysis identified TCR clones with differential memory- or effector-fate biases during …

Antimicrobial Activity Of Cat Flea (Ctenocephalides Felis) Gut Proteins On Different Days After Blood Feeding, Dhruva K. Karnik

Honors College Theses

Cat fleas (Ctenocephalides felis) are a blood-feeding ectoparasitic insect and a common domestic pest found throughout the world. Because of their reliance on host blood, fleas are exposed to blood-borne pathogens; however, the flea gut lumen is a hostile environment for microbial colonization. For example, the gut epithelia differentially express immune genes in response to feeding. In the present study, we measured the antimicrobial activity of gut proteins from cat fleas at different days after feeding (2, 5, 7, and 14). Dissected flea guts were homogenized, passed through a syringe filter, and measured in a protein assay kit. …

Ectoparasites Of The Critically Endangered Green Sawfish Pristis Zijsron And Sympatric Elasmobranchs In Western Australia, Jack Ingelbrecht, Karissa O. Lear, Storm B. Martin, Alan J. Lymbery, Bradley M. Norman, Geoffrey A. Boxshall, David L. Morgan

Harold W. Manter Laboratory of Parasitology: Library Materials

This study reports the metazoan ectoparasite fauna of juvenile Critically Endangered green sawfish, Pristis zijsron, and sympatric elasmobranchs in Western Australia. Five parasite taxa were found on 76 screened P. zijsron: Caligus furcisetifer (Copepoda: Caligidae), Dermopristis pterophila (Monogenea: Microbothriidae), Branchellion plicobranchus and Stibarobdella macrothela (Hirudinea: Piscicolidae), and praniza larvae of an unidentified gnathiid isopod. Only C. furcisetifer and D. pterophila were common, exhibiting discrepant site-specificity, with C. furcisetifer occurring mostly on the head and rostrum, and D. pterophila around the pectoral and pelvic fins. Intensity of infection for C. furcisetifer and D. pterophila increased with host total length and …

Euhaplorchis Sp. A Effect On Social Behavior And Familiarity Of Gulf Killifish (Fundulus Grandis), Hannah Bauman

All HCAS Student Capstones, Theses, and Dissertations

Trophically transmitted parasites may manipulate their hosts’ phenotype (e.g., behavior, physiology, morphology) to increase the likelihood of transmission to the definitive host. In fishes, stable social groups develop familiarity over time through repeated interactions among individuals, and social preferences are often developed due to familiarity. Consequently, fishes often shoal with familiar fishes, a behavior that is likely to be protective against predation. Parasites may alter fish social dynamics in two ways: by decreasing association with familiar individuals, thereby isolating infected fish and making them more susceptible to predation by definitive hosts; and/or by incentivizing uninfected individuals to avoid infected fish …

Investigating Vital Neutrophil Extracellular Trap Pathogen Response In Neutropenic Individuals, Ryan Illig

Thinking Matters Symposium

Neutrophils, also called polymorphonuclear leukocytes (PMNs), constitute the majority of innate immune cells. These cells possess a complex arsenal of functions that allow them to detect and eliminate a broad spectrum of pathogens. Neutropenia is characterized by decreased levels of neutrophils in the bloodstream, typically falling below the normal range. Moderate to severe neutropenia can increase the risk of pathogenic infections and without treatment can be life-threatening. Although the concentration of neutrophils in neutropenic individuals is decreased, upon activation, neutrophils still release neutrophil extracellular traps (NETs). NETs are pivotal in combating a spectrum of pathogens through their non-selective nature. Overreactive …

Cultivating Excellence: A Literature Review On Harnessing The Power Of The Gut Microbiome For Athletic Performance, Maya Katharine Dean

Honors Projects

The interplay between our gut microbiome and health is immense. This literature review analyzes the current research assessing the interplay between gut microbiome and athletic performance. Knowing how to improve gut microbial diversity via nutrition and supplementation can take athletic performance to the next level; namely improvements in immune, mental, and physical health.

Regulation And Therapeutic Targeting Of Virus-Specific Resident Memory T Cells, Jordan Fredriksen Isaacs

Dartmouth College Ph.D Dissertations

CD8+ T cells are critical to the immune response to pathogens, as they kill infected cells and generate immunologic memory. Following infection, antigen-specific T cells expand approximately 10,000-fold and migrate to sites of inflammation in order to clear the pathogen. Once infection is resolved, a small pool of memory T cells persist in circulation and within tissues ready to respond rapidly upon re-exposure. Given the importance of CD8+ T cells, significant efforts have been made over the years to better understand how different memory T cell subsets are established, maintained, and regulated. The most recently identified subset, resident memory T …

An Exploration Of The Effectiveness Of Xanthorrhiza Simplicissima And Its Secondary Alkaloids As Antibiotics Against Staphylococcus Aureus With The Use Of Reserpine, Donald Bothe, Savita Chaurasia

Undergraduate Theses

Xanthorhiza simplicissima is a plant that is steeped in medical history. It has been used for hundreds of years by the Native Americans, and later by the Europeans, of Appalachia for its medicinal properties. One of the most useful medical applications of this plant are its antibiotic properties, as typified by its use as a tea that was consumed to treat mouth sores. These antibiotic properties can be attributed to some of its secondary alkaloids such as berberine, liriodenine, oxyacanthine, and magnoflorine. These compounds have been studied in other systems; however, oxyacanthine and magnoflorine have not been researched in tandem …