Immunopathology Commons^™

Identification And Characterization Of Novel Immune Modulating Genes In Parkinson's Disease, Kathleen Chaundy Paul Murphy

Dartmouth College Ph.D Dissertations

Parkinson’s disease (PD) is a progressive age-related neurodegenerative disorder characterized by both motor and non-motor symptoms. The poorly understood prodromal period, decades-long progression, and disease-phenotype heterogeneity continue to impede the development of preventive and curative therapies. A growing appreciation of immune system changes during the progression of PD suggests that evaluating peripheral immune cells may help identify signatures relevant to disease etiology. We aimed to expand our understanding of the peripheral immune compartment in PD via two lines of investigation: (1) by employing single-cell RNA sequencing to profile the transcriptomes of peripheral blood mononuclear cells (PBMCs) from a cohort of …

Examining The Ligands, Location, And Function Of Toll-Like Receptor 10, Kiefer Keanu Tam

Master's Theses

Toll-like receptors are a class of innate immune pattern recognition receptors that detect pathogen-associated molecular patterns and regulate downstream inflammatory responses. Toll-like receptor 10 remains the only human TLR whose ligand specificity, cellular localization, and immunological function are not fully defined. Emerging evidence suggests that TLR10 may play an anti-inflammatory role and can heterodimerize with TLR2 to modulate immune signaling. Previous studies from our laboratory demonstrated that stimulation with heat-killed Mycobacterium tuberculosis promotes TLR2-TLR10 heterodimerization and trafficking to the cell surface. In this study, we expanded our ligand panel to include additional gram-positive bacteria, particularly anti-inflammatory probiotic species, to further …

Environmental Mercury Alters Immune Pathways Linked To Autoimmune Risk In Mice Mirroring Humans, Maurgan Lee, Paul Stemmer, Randall Gill, Allen Rosenspire, Anil Aranha, Heather Gibson

Medical Student Research Symposium

Background and Purpose: Mercury is a pervasive environmental contaminant, and human epidemiologic studies have linked chronic low-level exposure to increased autoimmune disease-risk. Dysregulated lymphocyte activation and impaired signaling tolerance are central mechanisms in human autoimmunity. Protein phosphorylation governs lymphocyte differentiation and function, alterations in phosphoproteomic networks may represent a signature of immune disruption. This study evaluates how low dose mercury exposure modifies B and T cell abundance and intracellular signaling patterns in BALB/c and Diversity Outbred (DO) mice.

Methods: BALB/c and DO mice were exposed to low dose HgCl2 in their water for two weeks or provided standard water controls. …

Impact Of The Dose And The Number Of Transmitted/Founder Viruses On Siv Dynamics, Sunil Maity, Vitaly V. Ganusov

Biology and Medicine Through Mathematics Conference

No abstract provided.

The Risk Of Bpa In B Lymphocyte-Mediated Autoimmunity, Mario J. Palacios

Senior Honors Theses

Autoimmune disorders disproportionately affect females, a bias largely attributed to estrogen's modulation of B lymphocyte development and tolerance. Bisphenol A (BPA), a common plastic monomer, shows estrogenic activity and acts as an endocrine disruptor and epigenetic modifier. This thesis examines how BPA may increase autoimmune risk by mimicking estrogen such that it can excite estrogen receptors which rescue autoreactive B lymphocytes from apoptosis. While direct research linking BPA to B lymphocyte-mediated autoimmunity is limited, understanding BPA’s course of action in B lymphocytes is critical for addressing the rising prevalence of autoimmune diseases and its possible link to the increased and …

Cell-Free Mitochondrial Dna (Mtdna) Triggers Vascular Dysfunction Via Toll-Like Receptor 9 (Tlr9)-Dependent Activation Of Inflammasomes, Mohin Amin

Senior Theses

Hypertension is the leading global risk factor for mortality and is closely associated with vascular inflammation and dysfunction. Damaged mitochondria release cell-free mitochondrial DNA (cf-mtDNA), which activates toll-like receptor 9 (TLR9). The binding of TLR9 to mtDNA activates the NLRP3 inflammasome pathway, promoting the release of pro-inflammatory cytokines via gasdermin D (GSDMD), therefore worsening inflammation. However, the mechanisms linking mitochondrial injury to inflammation-induced vascular dysfunction remain unclear. We hypothesize that cf-mtDNA triggers TLR9-dependent NLRP3 inflammasome activation contributing to vascular and endothelial dysfunction. To assess that, adult male C57BL/6 were exposed to 28 consecutive days of chronic unpredictable stress (CUS) or …

Ifnγ-Induced Antigen Loss In Chimeric Antigen Receptor-T Cell Therapy, Miao Cao, Jasmine Alvarez, Ramkrishna Mitra, Michael Xu, Trevor R. Baybutt, Zhengyang Sun, Oluwatobiloba Taylor, Allison Doermann, Ross E Staudt, Scott A. Waldman, Adam E. Snook

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

INTRODUCTION: FDA-approved chimeric antigen receptor (CAR)-expressing T cell therapies (CARTs) have revolutionized the treatment of blood cancers. Yet none have been successful for "solid" tumors, such as colorectal cancer (CRC), the 2nd leading cause of cancer deaths. Guanylyl cyclase C (GUCY2C) has emerged as a clinical-stage target for CART and bispecific T-cell engager (BiTE) therapies in CRC. IFNγ has been canonically recognized as beneficial for the effector functions of T cells by enhancing antigen processing and HLA presentation and is essential for CART targeting of solid malignancies by inducing adhesion molecule expression for synapse stabilization.

METHODS: Using

RESULTS: We identified …

Cytotoxic And Antimicrobial Effects Of Plant-Derived Compounds Used In Traditional Chinese Medicine, Amanda Ly, Diane Sun, Shelbi Salinas, Victor M. Jimenez

Annual Research Symposium

No abstract provided.

Comparative Spatial Biology: A Cross-Species Analysis Of Canine Oral Cancers As Models For Human Disease, Ram Pradhyumnan

Honors Undergraduate Theses

Oral squamous cell carcinoma (OSCC), one of the most common malignancies of the oral cavity, remains a clinically challenging disease due to its aggressive behavior, late-stage diagnosis, and limited improvements in therapeutic outcomes over recent decades. A significant barrier to progress in OSCC research and treatment is the lack of suitable preclinical models that recapitulate the complexity and natural progression of the disease. Most current models—including cell lines, xenografts, and genetically engineered mice—fail to capture key features such as the spatial organization of tumor epithelium, interactions with an intact immune system, and the stepwise evolution from normal mucosa to invasive …

The Influence Of Tert-Butylhydroquinone (Tbhq) On Acod1/Irg1-Driven Inflammatory Pathways, Alyssa M. Whisel

All Dissertations

The demand for processed foods has led to increased use of synthetic phenolic antioxidants (SPAs), notably tert-butylhydroquinone (TBHQ), to inhibit lipid oxidation and prolong shelf life. While TBHQ is deemed safe at regulated levels, concerns arise from studies indicating potential adverse effects such as oxidative stress, genotoxicity, and impaired immune function. To investigate TBHQ's immunomodulatory effects, RAW 264.7 murine macrophages were pre-treated with TBHQ and subsequently stimulated with lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (poly I:C, PIC) to simulate bacterial or viral challenges. Results demonstrated that TBHQ at high non-cytotoxic doses reduced nitric oxide and IL-10 production while promoting phagocytosis and …

Ybx1-Mediated Activation Of Srebp2 Drives Sorafenib Resistance Via Cholesterol Biosynthesis In Hepatocellular Carcinoma, Veerababu Nagati, Dennis Kwabiah, Yamile Abuchard, Ana Ayala Pazzi, Shaibir Hussain, Salique H. Shaham, Manish Tripathi

Research Colloquium

Background: Hepatocellular carcinoma (HCC) is an aggressive, largely chemo-resistant cancer with a poor prognosis and is the leading cause of cancer-related deaths worldwide. Currently, there is no effective systemic chemotherapy for HCC. Sorafenib is a multikinase inhibitor commonly used as the first-line treatment for advanced HCC. However, acquired drug resistance significantly limits its clinical effectiveness. The Y-box binding protein (YBX1) is an oncogenic RNA-binding protein found to be upregulated in sorafenib-resistant HCC cells and tissues.

Methods: HCC model SK Hep1, YBX1 overexpression, and knockdown cells were prepared by transient transfection with puromycin selection, and stable cell lines were established through …

Computational Frameworks To Unravel The Immune Landscape, Shan He

Dissertations and Theses (Open Access)

Recent advances in immunotherapy, including immune checkpoint blockade (ICB) and adoptive cell therapy, face challenges such as resistance and immune-related adverse events, partly due to our limited understanding of the immune signaling pathways. While high- throughput genomic data provide unprecedented resolution into these immune pathways, their full potential is limited by the lack of well-annotated, context-specific immune gene sets. To address this need, I developed a workflow to construct immune gene sets by integrating RNA- seq datasets and performing decomposition. Using this approach, I constructed 28 immune- specific gene sets from 83 bulk RNA-seq datasets and 12 Natural Killer (NK) …

Immune Regulation In Fungal Airway Inflammation And Host Defense, Ruoning Wang

Biomedical Sciences ETDs

Asthma is a chronic inflammatory disease of the lungs characterized by complex pathophysiological mechanisms and diverse endotypes, primarily categorized as T helper type 2 cell (Th2)-high and Th2-low asthma. Despite significant advances in understanding asthma pathogenesis, the mechanisms governing the pulmonary immune system’s response to external challenges have not been fully understood. To address these gaps, this comprehensive project was designed to investigate the interplay between fungal infections and specific CD4⁺ T cell populations in asthma. Our findings suggest that fungal infections can contribute to neutrophilic asthma by promoting the migration of platelet-myeloid aggregates into the lungs. We also …

Developing A Murine Model To Investigate The Mechanisms Of Peanut, Cashew, Shrimp Multifood Allergy, Aaron Wilson

NYMC Student Theses and Dissertations

Approximately 32 million people in the United States have food allergies, which is approximately 10 percent of the population. Food allergies can be mild, moderate, or even severe, resulting in anaphylaxis. The most predominant food groups that trigger food allergies include peanuts, tree nuts, fish, and shellfish. Peanuts and tree nuts have some similarities in protein structure. Shellfish is not associated with the protein properties of peanuts or tree nuts, it is the leading cause of adult anaphylaxis and often co-exist with peanut and tree nut allergies Currently, there are few studies that have established a murine model for allergy …

Chronic Inflammation: The Link Between A High Added Sugar Diet And Disease, Anna Collins

Senior Honors Theses

The modern diet includes many processed foods that contain added sugars, resulting in a significant increase in daily glucose and fructose consumption. Considering this, there is an increased effort to uncover the effects of excess sugar intake on the body’s health and metabolism. Strong evidence supports the connection between a high added sugar diet and the presence of chronic, low-grade inflammation due to cellular distress and metabolic dysfunction. Prolonged inflammatory responses are linked to tissue damage and the development of various metabolic diseases that are prevalent in modern society, such as obesity, fatty liver disease, cardiovascular disease, and type 2 …

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 …

Excess Fructose In High-Fructose Corn Syrup Reduces Cell Viability & Promotes Nitric Oxide Release In Raw 264.7 Macrophages, Renzo F. Galarza, Edward L. Villegas

Research and Creativity Symposium

High-fructose corn syrup (HFCS) is an artificial sweetener that contains slightly higher concentrations of fructose compared to standard sucrose. It has been linked to an increased risk of obesity, type 2 diabetes, cardiovascular disease, and fatty liver disease. While both HFCS and sucrose are widely used sweeteners, growing evidence suggests they may differ in their inflammatory potential. We sought to understand the effects of elevated fructose on RAW 264.7 macrophages. To investigate these effects, we treated the cells with either a sucrose solution or a
solution designed to mimic high-fructose corn syrup. Lipopolysaccharide (LPS) stimulation was used to model innate …

Pseudomonas Aeruginosa Exoenzyme Y Enzymatic Activity Inhibits Exoenzyme S-Induced Caspase Activation But Not Cytotoxicity In Pulmonary Microvascular Endothelial Cells, Connor Holm

Honors Theses

Pseudomonas aeruginosa (P. aeruginosa) is the most common cause of ventilator-associated pneumonia in intensive care unit patients. P. aeruginosa utilizes a type III secretion system that injects exoenzymes U, S, T, and/or Y into the host cell cytosol. A majority of clinically isolated P. aeruginosa strains express ExoY often in combination with ExoU and ExoT, or ExoS and ExoT. Host signaling mechanisms in response to intoxication with individual exoenzymes have been extensively studied, yet little is known about host cell response to co-intoxication. In this study, pulmonary microvascular endothelial cells (PMVECs) were infected with P. aeruginosa strains expressing different combinations …

Clinical Characteristics And Outcomes Of Pediatric Staphylococcal Scalded Skin Syndrome (Ssss) At An Inner-City Tertiary Care Center, Nina Kb Gust Md, Ashley Frei Bs, Rebecca M. Adams Bs, Elika Ridelman Phd, Christina Shanti Md, Ronald Thomas Phd, Jocelyn Y. Ang Md

Medical Student Research Symposium

Introduction

Staphylococcal Scalded Skin Syndrome (SSSS) is a blistering skin condition caused by a toxin-producing staphylococcus species. Epidemiologic studies on pediatric SSSS in the United States are limited, with a reported incidence of 7.67 cases per million children and 45.1 per million infants. Immature renal function, lack of protective antibodies, and increased exotoxin target desmoglein-1 are hypothesized to increase incidence in younger children. We aimed to determine clinical and microbiological characteristics of pediatric SSSS and factors that could help predict disease severity.

Methods

A retrospective chart review was performed for admitted patients under 18 years old diagnosed with SSSS from …

Investigating The Ability Of Foxo1 To Maintain Stem Cells, Stella A. Rios, Megan E. Keniry

Research Symposium

Background: Our group discovered that FOXO transcription factors drive stem gene expression in cancer to promote aggressiveness. Work by our group and others demonstrated that FOXO factors universally maintain stem cells including in cancer, embryonic, hematogenic and neuronal contents. Our current efforts are delineating the molecular underpinnings by which FOXO factors halt differentiation to maintain stem cells.

In this project, we are employing myoblasts as a valuable model to examine how Foxo1 maintains stem cells. Foxo1-regulated genes in myoblasts closely parallel its targets in glioblastoma and basal breast cancer stem cells, including targets such as Leukemia Inhibitory Factor, …