Medical Immunology Commons^™

When Nutrition Fails: Modeling Protein Malnutrition-Driven Vulnerability In Hepatic Drug Metabolism And Inflammatory Stress, Vijitha D. Kantety, Victor Jiminez Jr.

Annual Research Symposium

Background

Protein malnutrition remains a major global health problem and frequently co-occurs with alcohol use, opioid exposure, and infectious disease, particularly in low- and middle-income settings. The liver is central to both metabolism and inflammatory regulation, yet the effects of a malnutrition-like nutrient environment on hepatic responses to combined metabolic and inflammatory insults are not well defined. Cytochrome P450 3A4 (CYP3A4), a key enzyme involved in opioid metabolism, is highly sensitive to inflammatory signaling and may be especially vulnerable under conditions of nutritional deficiency. This project aims to 1) develop an in vitro model of nutritionally competent versus amino acid–restricted …

Chronic Alcohol Consumption Enhances The Differentiation Capacity Of Hematopoietic Stem And Progenitor Cells Into Osteoclast Precursors, Hami Hemati, Madison B. Blanton, Jude Koura, Rupak Khadka, Kathleen A. Grant, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Chronic alcohol consumption (CAC) is associated with an enhanced risk of bone fracture, reduced bone density, and osteoporosis. In a rhesus macaque model of voluntary ethanol consumption, CAC induces functional, transcriptomic, and epigenomic changes in hematopoietic stem and progenitor cells (HSPCs) and their resultant monocytes/macrophages, skewing them toward a hyper-inflammatory response. In the present study, those studies were extended to investigate alterations in osteoclast development, which, in postnatal life, differentiate from HSPCs and play a critical role in maintaining bone homeostasis. Spectral flow cytometry revealed a skewing of HSPCs toward granulocyte-monocyte progenitors in the CAC group, consistent with an increased …

Chronic Alcohol Consumption Reprograms Osteoclast Lineage Communications To Promote Osteoclastogenesis, Hami Hemati, Brianna M. Doratt, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Chronic alcohol consumption increases the risk of osteoporosis and fracture by disrupting bone remodeling, in part by enhancing osteoclastogenesis. However, the cellular mechanisms underlying this process remain incompletely defined. We analyzed scRNA-seq data from osteoclasts differentiated in vitro from bone marrow mononuclear cells obtained from macaques following 12 months of chronic ethanol or isocaloric control solution consumption. Module scoring, trajectory inference with generalized additive modeling (tradeSeq), and CellChat-based analyses of intercellular communication were applied to uncover ethanol-induced changes in metabolic reprogramming, lineage progression, and signaling network dynamics. Module scoring indicated metabolic reprogramming toward oxidative phosphorylation, with reduced glycolytic, migratory, and …

Alcohol Consumption Exacerbates High-Fat Diet- Mediated Disruptions In Myelopoiesis And Osteoclastogenesis In Mouse Models Of Metabolic Dysfunction-Associated Liver Diseases, Hami Hemati, Madison B. Blanton, Lauren Rutt, Nicholas Keiran, Rebecca Geron, Florence Lima, Rebecca L. Mccullough, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Objective: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Alcohol-related Liver Disease (MetALD) exhibit systemic immune abnormalities. Given that such immune dysregulation is closely linked to the skeletal complications frequently observed in MASLD and MetALD, we sought to comprehensively characterize the bone marrow hematopoietic compartment and its link to osteoclastogenesis.

Methods: We utilized bone marrow from mouse models of MASLD (high-fat diet, HFD) and MetALD (high-fat diet plus ethanol, HFD+EtOH), followed by flow cytometric analysis to phenotype hematopoietic stem and progenitor cells (HSPCs), as well as in vitro and in vivo assays to evaluate osteoclastogenesis.

Results: We found that …

Transcriptional Signatures Of Rapid Protection From Sudan Virus Infection By A Single Dose Of A Vesicular Stomatitis Virus-Based Vaccine, Brianna M. Doratt, Sheridan B. Wagner, Delphine C. Malherbe, Gregory T. Smith, Andrea Marzi, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Sudan virus (SUDV) has caused multiple outbreaks of human disease with case fatality rates ranging from 41 to 100%. We have previously shown that a single vaccination with a recombinant vesicular stomatitis virus-based vaccine expressing the SUDV-Gulu glycoprotein (VSV-SUDV) prevented clinical and fatal disease from lethal SUDV challenge in cynomolgus macaques. With the high probability of future outbreaks, it is critical to determine the molecular mechanisms of VSV-SUDV-mediated protection and the ability to impart rapid protection against SUDV infection. In this study, RNA from whole blood samples obtained from nine cynomolgus macaques that were challenged with SUDV-Gulu post-vaccination with either …

Characterizing Immune Perturbations In Peripheral Blood Following The East Palestine, Ohio Train Derailment, Sheridan B. Wagner, Hami Hemati, Siva Gandhapudi, Timothy J. Hilbert, Candace J. Brancato, Erin N. Haynes, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background: The East Palestine, Ohio, train derailment on February 3rd, 2023, resulted in the exposure of residents and the surrounding area to numerous hazardous chemicals, which included known acute irritants and human carcinogens. Despite evacuation and cleanup, both residents and responders reported high occurrences of symptoms associated with exposure in the months following, such as eye, skin, and respiratory irritation, headaches, and fatigue. The long-term health consequences for residents remain uncertain.

Objective: To assess the potential for immune perturbations resulting from the exposure, we performed a broad investigation of circulating immune cells and mediators from residents of East Palestine, OH, …

Combinatorial Immunotherapy Drives Exhaustion In Tumor Antigen–Specific Cd8+ T Cells Within The Mouse Renal Tumor Microenvironment, Holly R. Stephens, Elizabeth Elkins, Jing Li, Zoey N. Swalley, Henry Nnaemeka Ogbonna, Pia Muri, Zachary Roberts, Francesca R. Dempsey, Md Akkas Ali, Md Hasanul Banna Siam, Richard Kirkman, Jianqing Zhang, Sunil Sudarshan, Daniel J. Tyrrell, Hubert M. Tse, Daniel L. Smith Jr, Lyse A. Norian

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Immunotherapies have greatly improved outcomes for patients with renal cell carcinoma (RCC), yet response rates remain suboptimal and the factors promoting therapy resistance versus sensitivity are incompletely understood. Currently, no preclinical model of orthotopic renal cancer exists that permits evaluation of tumor antigen–specific (TAS) CD8⁺ tumor-infiltrating lymphocytes (TILs). To address this deficiency, we developed a mouse renal cancer model that permits tracking of adoptively transferred TAS CD8⁺ T cells. Renca-LUC tumor cells were transduced to express tumor ERK (tERK), a model antigen expressing a one-amino-acid change from wild-type ERK, resulting in recognition by tERK/H-2K^d-specific DUC Thy1.1 …

Granulomatous Cellular Signatures In Nontuberculous And Tuberculous Mycobacterial Infections, Brianna M. Doratt, Ethan G. Napier, Mahdi Eskandarian Boroujeni, Sarah Douglas, Michael H. Davies, Luiz Bermudez, Eliot Spindel, Erin F. Mccaffrey, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM) are acid-fast bacilli that trigger granuloma formation, a hallmark immune response aimed at containing infection. While the biology of Mtb granulomas has been widely investigated, far less is known about granulomas caused by NTM infection, despite the increasing prevalence and clinical challenge of NTM cases worldwide. Because granulomas influence infection control, pathology, and treatment response, understanding their cellular organization and signaling is critical to improving therapeutic strategies. Therefore, we characterized granulomas formed following infection of rhesus macaques with Mycobacterium avium subsp. hominissuis (MAH) and compared them to granulomas from cynomolgus macaques infected with …

Glycoprotein-Specific Transcriptional Response Contributes To Differential Vaccine Protection Against Lethal Ebola Virus Infection, Sheridan B. Wagner, Delphine C. Malherbe, Ethan G. Napier, Andrea Marzi, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Since the West African Ebola virus (EBOV) epidemic in 2014-2016, recurrent outbreaks of the EBOV-Makona variant have been driven by recrudescence and human-to-human transmission emphasizing the need for effective vaccination strategies. A live-attenuated recombinant vesicular stomatitis virus (VSV)-based vaccine expressing the EBOV-Kikwit variant glycoprotein (VSV-Kik) received FDA approval in December 2019 and provides complete, rapid protection against EBOV-Makona as early as 7 days post-vaccination (DPV). During the 2018-2020 Ebola outbreak, the VSV-Kik vaccine, known as ERVEBO, was administered to lower-risk individuals at a 5-fold dose reduction of the standard 2 × 10 ⁷ PFU to provide broader population protection. Identification …

A Novel Tyrosine Kinase Axis In Innate Immune Signaling, Santanu Das, Pracheta Sengupta, Manoj Veleeparambil, Saurabh Chattopadhyay

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Tyrosine phosphorylation has emerged as a central regulatory mechanism in innate immunity. Building on our recent studies that Syk and EGFR sequentially phosphorylate TLR9 to fully activate it, we discuss how similar mechanisms operate across other Toll-like receptors and the cytosolic DNA sensor STING. Evidence from complementary systems reveals that receptor and nonreceptor tyrosine kinases, including Src-family kinases, Syk, BTK, and EGFR, form an integrated signaling network that triggers receptor activation, trafficking, and downstream gene expression. Scavenger receptors such as SR-A further drive this kinase cascade by coordinating viral recognition to TLR activation. These observations reveal a novel ‘tyrosine kinase …

Maternal Opioid Use Disorder And Hepatitis C Infection In Pregnancy Reshape The Peripheral Immune Landscape At Term, Brianna M. Doratt, Heather E. True, Sheridan B. Wagner, Delphine C. Malherbe, Zachary M. Reynolds, Cynthia Cockerham, John O'Brien, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background: Pregnancy requires precisely timed immune adaptations to maintain foetal tolerance while enabling timely initiation of labour, a process often conceptualised as the ‘immune clock’ of pregnancy. Disruption of this immune clock contributes to adverse obstetric outcomes. While maternal opioid use disorder (OUD) is a recognised risk factor for poor maternal and neonatal health, its impact on maternal immune landscape at delivery remains poorly understood.

Methods: We analysed peripheral blood collected from pregnant individuals with and without OUD at time of admission for delivery before the onset of active labour. We employed multiparameter flow cytometry, cytokine profiling, and single-cell-RNA sequencing …

Light-Induced Oslike1 Phosphorylation Enhances Rice Resistance Against Blast Disease, Jiangtao Liu, Lei Su, Wenya Wang, Jintao Wang, Weizhong Chen, Zhixiang Yang, Leiyun Yang, Gang Li, Xinyu Liu, Haifeng Zhang, Zhongqiang Qi, Yongfeng Liu, Yuqiang Liu, Ping Wang, Muxing Liu, Zhengguang Zhang

School of Graduate Studies Faculty Publications

Rice blast caused by Magnaporthe oryzae poses a major threat to world food supply. Conditions conducive to the disease include insufficient light. Our previous studies found that light-dependent phosphorylation of light-harvesting complex II protein (LHCB5) mediates rice immunity; however, the underlying mechanisms, in particular, the upstream regulators of LHCB5 phosphorylation, remain unknown. Here, we show that OsLIKE1 functions as a lectin receptor-like kinase (LecRLK) to play a critical role in rice resistance against M. oryzae. OsLIKE1 interacts with and phosphorylates LHCB5. In addition, we find two phosphorylation sites in the kinase domain of OsLIKE1 important for its auto-phosphorylation and phosphorylation …

Advancing Peptide-Based Vaccines Against Candida: A Comparative Perspective On Liposomal And Synthetic Formulations, Hong Xin

School of Graduate Studies Faculty Publications

The growing threat of multidrug-resistant fungal pathogens, especially Candida auris, has underscored the need for effective antifungal vaccines. This commentary highlights recent advances in peptide-based vaccination using the SNAP (Spontaneous Nanoliposome Antigen Presentation) platform, focusing on the FM-SNAP vaccine, a bivalent liposomal formulation targeting the surface-expressed peptides fructose bisphosphate aldolase (Fba) and methionine synthase (Met6). Compared to earlier constructs such as MP12, FM-SNAP achieves superior immunogenicity and long-lasting protection at lower antigen doses. It elicits balanced Th1/Th2 cytokine responses and demonstrates durable efficacy in both immunocompetent and complement-deficient mouse models. The platform's compatibility with clinically approved adjuvants (MPLA and QS-21), …

Bcg Vaccine-Induced Innate And Adaptive Pulmonary Immunity Correlating With Protective Efficacy Against Mycobacterium Tuberculosis In The Lungs, Mayank Khanna, Alistair J. Ramsay

School of Graduate Studies Faculty Publications

Background/Objectives: Effective prophylaxis for Mycobacterium tuberculosis (Mtb) requires greater understanding of immune correlates of protection. With renewed interest in BCG as an Mtb vaccine, particularly via the intravenous (IV) route, our objective was to characterize both innate and adaptive immune correlates of vaccine-induced pulmonary immunity as potential biomarkers for protective efficacy in a murine model of Mtb infection. Methods: Mice were given BCG via different routes and some boosted with recombinant virus constructs encoding Mtb Ag85B. Responding innate lymphoid cell (ILC) populations, T cells and B cells were analyzed by fluorescence activated cell sorting (FACS) for surface markers and by …

Distinct Echinocandin Responses Of Candida Albicans And Candida Auris Cell Walls Revealed By Solid-State Nmr, Malitha C. Dickwella Widanage, Kalpana Singh, Jizhou Li, Jayasubba Reddy Yarava, Faith J. Scott, Yifan Xu, Neil A.R. Gow, Frederic Mentink-Vigier, Ping Wang, Frederic Lamoth, Tuo Wang

School of Graduate Studies Faculty Publications

Invasive candidiasis affects 1.6 million people annually, with high mortality among immunocompromised and hospitalized patients. Echinocandins are frontline antifungals, but rising resistance limits their efficacy. Here, we show that Candida albicans and multidrug-resistant Candida auris share a conserved cell wall architecture yet differ markedly in their adaptive responses to echinocandins. Solid-state NMR reveals that both species possess a rigid inner layer of tightly associated chitin microfibrils and β−1,3-glucans, supported by a flexible matrix of β−1,6-glucans and additional β−1,3-glucans. Outer mannan fibrils rely on α−1,2-linked sidechains to maintain contact with the inner wall. In both species, caspofungin rigidifies β−1,6-glucans and mannan …

Characterization Of Immunogenicity Of Hiv Mrna Vaccine In Humanized Mice, Omoyeni Precious Adejare

Biotechnology Theses

Human Immunodeficiency Virus (HIV) remains a leading global cause of mortality. Despite decades of research, a definitive cure or an effective vaccine for HIV infection has yet to be discovered. The major target for HIV vaccine development is the envelope (Env) trimeric protein that is responsible for host cell attachment and fusion. This comprises gp120 and the transmembrane gp41. Gp140, a truncated form of gp160(full envelope trimer) lacks the transmembrane and cytoplasmic domains of gp41, closely mimics the native HIV envelope has been shown to enhance the induction of broadly neutralizing antibodies (BnAbs) when used as protein vaccine in previous …

Monoclonal Antibodies Targeting Candida Disrupt Biofilms And Inhibit Growth Across Global Clinical Isolates, Jonothan Rosario-Colon, Karen Eberle, Hong Xin

School of Graduate Studies Faculty Publications

Candida species are a major cause of severe fungal infections, particularly in immunocompromised individuals and hospitalized patients. Among these, Candida auris stands out as an emerging “superbug”, responsible for life-threatening bloodstream infections with mortality rates up to 60%. This multidrug-resistant, hospital-acquired pathogen has been declared a serious global health threat, complicating effective treatment and increasing mortality risks. Our research has identified universal monoclonal antibodies (mAbs) targeting Candida albicans cell wall epitopes, which are highly homologous to those in other pathogenic Candida species, including C. auris. Passive transfer of mAbs—C3.1 (anti-β-1,2-mannotriose) and 9F2 (anti-phosphoglycerate kinase 1)—significantly extended survival and improved fungal …

Exploring The Mechanisms Of Varicella-Zoster Virus Pathogenesis And Its Potential Role In Oncogenesis, Fernando Cisneros, Blake Martin

Research Symposium

Background: Varicella-zoster virus (VZV) is a highly prevalent pathogen primarily recognized for causing chickenpox during primary infection and herpes zoster (HZ), also known as shingles, upon reactivation. While post-infectious complications of VZV, such as encephalitis, pneumonia, and post-herpetic neuralgia, are well-established, recent large population-based studies suggest that HZ may increase the risk of occult cancers. Emerging evidence suggests that VZV may modulate key oncogenic pathways, such as the inhibition of apoptosis, alteration of cell cycle regulatory enzymes, and interference with immunosurveillance, which could potentially promote cancer development. These findings indicate that VZV’s role in cancer biology may involve direct cellular …

Extracellular Vesicles Released By All Patients Contain Hne-Adducted Proteins: Implications Of Collateral Damage., Jenni Ho, Suriyan Sukati, Tamara Taylor, Sherry Carter, Brittany Fuller, Amy Marmo, Caryn Sorge, John D'Orazio, D Allan Butterfield, Subbarao Bondada, Heidi Weiss, Daret K St Clair, Luksana Chaiswing

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Off-target neuronal injury is a serious side-effect observed in cancer survivors. It has previously been shown that pediatric acute lymphoblastic leukemia (ALL) survivors have a decline in neurocognition compared to healthy age-matched counterparts. Elevated oxidative stress has been documented to be a mediator in off-target tissue damage in cancer survivors. Early detection of oxidative stress markers may provide an opportunity to prevent off-target tissue damage. Extracellular vesicles (EVs) have surfaced as a potential diagnostic tool due to molecular cargo they contain. We investigated the potential for EVs to be a sensitive indicator of oxidative stress and off-target tissue damage by …

Characterization Of Vaccine-Enhanced Humoral Immune Responses Against Emergent Sars-Cov-2 Variants In A Convalescent Cohort, Jared Sheehan, Amber J. Trauth, Michael E. Hagensee, Alistair J. Ramsay

School of Graduate Studies Faculty Publications

Vaccination of COVID-19–convalescent individuals may generate ‘hybrid’ immunity of enhanced magnitude, durability, and cross-reactive breadth. Our primary goal was to characterize hybrid antibody (Ab) responses in a patient cohort infected with ancestral Wuhan-Hu-1 virus and vaccinated between 6 and 10 months later with the Wuhan-Hu-1–based BNT162b2 mRNA vaccine. We were particularly interested in determining the efficacy of neutralizing Ab responses against subsequently emergent SARS-CoV-2 variants. Sera collected at 3-monthly intervals over a period of 12 months were analyzed by ELISA for SARS-CoV-2 RBD–specific Ab responses, and also for neutralizing Ab activity using pseudovirus-based neutralization assays. We found that convalescent RBD-reactive …

In Vivo Evaluation Of Novel Nanoparticles And Repurposed Pharmaceuticals To Combat Antimicrobial Resistance, Sarah E. Evans

Theses, Dissertations and Capstones

In a 2019 report by the Centers for Disease Control and Prevention (CDC), infections resistant to antibiotic treatment amount to about three million infections and 48,000 deaths. Antimicrobial resistance is an escalating global threat as existing antibiotics lose efficacy over time. The project described is focused on partnering with pharmaceutical researchers and producers to test new nanoparticle-based or repurposed compounds. The central hypothesis of this thesis is that pharmaceutical formulations such as nanoparticles may provide a cost-effective means of combating the emerging antimicrobial resistance. The nanoparticle compounds allowed for a wide range of customization for the pharmaceutical design, since the …

Borreliosis And Doxycycline Treatment Disrupt Gut Microbiota And Immune Responses In Nonhuman Primates, Ethan G. Napier, Isaac R. Cinco, Sheridan B. Wagner, Ethan V. Stuart, Qi Qiao, Joshua Taylor, Brian Stevenson, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Borrelia burgdorferi (Bb) is the spirochete that causes Lyme disease (LD). Transmission to humans occurs via bites of infected Ixodes spp. ticks. Doxycycline is often used to treat LD patients, which is sometimes delayed due to current diagnostic challenges. Recently, several lines of evidence show dysbiosis of the gut microbiome in LD patients, which may be a host factor contributing to pathogenesis and symp tomology but is still an understudied area in the field. To address this knowledge gap, we longitudinally compared the immune response and gut microbial composi tion of Japanese macaques after intradermal infection with Bb strain 297 …

Chronic Alcohol Consumption Induces Phenotypic And Functional Alterations Consistent With A Hyper-Inflammatory State In Peripheral Blood Mononuclear Cell-Derived Microglia In A Rhesus Macaque Model, Hami Hemati, Madison B. Blanton, Heather E. True, Jude Koura, Rupak Khadka, Kathleen A. Grant, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Alcohol-induced dysregulation of microglial activity is associated with neuroinflammation, cognitive decline, heightened risk for neurodegenerative diseases, alcohol dependence, and escalation of alcohol drinking. Given the challenge of longitudinally sampling primary microglia, we optimized an in vitro method to differentiate peripheral blood mononuclear cells (PBMC) from rhesus macaque (RM) into induced microglia-like cells (RM-iMGLs). The RM-iMGLs displayed transcriptional profiles distinct from monocyte progenitors and closely resembling primary microglia. Notably, morphological features showed that differentiated RM-iMGLs derived from subjects with chronic alcohol consumption (CAC), while bigger, exhibited a bipolar-like morphology. Additionally, dysregulation in key inflammatory and regulatory markers, along with increased baseline …

Impact Of Obesity On The Gut Microbiome And Inflammatory Markers During Siv Infection And Antiretroviral Therapy, Casey M. Mcguire, Isaac R. Cinco, Diana Takahashi, Kristin A. Sauter, Melissa Kirigiti, Ilhem Messaoudi, Jonah B. Sacha, Charles T. Roberts, Paul Kievit

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Dysbiosis and impaired gut barrier integrity contribute to chronic immune activation associated with both obesity and HIV infection. Given the increased incidence of obesity in people living with HIV, we explored the impact of obesity on the gut microbiome and microbial translocation (MT) biomarkers during HIV infection and antiretroviral therapy (ART). Lean and obese rhesus macaques were infected with simian immunodeficiency virus (SIV) and subsequently treated with ART. Obese animals exhibited higher initial MT and inflammation biomarkers that remained constant throughout the study, while lean animals exhibited significant increases in these biomarkers that approached levels observed in obese animals. Lean …

Intracellular Survival Of Staphylococcus Aureus In Macrophages During Osteomyelitis, William A. Lathram, Christopher D. Radka

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Staphylococcus aureus, traditionally viewed as an extracellular pathogen, is increasingly recognized for its ability to persist intracellularly, particularly within macrophages. This intracellular lifestyle is central to osteomyelitis, a chronic bone infection characterized by persistent inflammation, bone destruction, and impaired repair. Within bone, S. aureus exploits macrophage plasticity by driving a shift from pro-inflammatory, bactericidal M1-like states to anti-inflammatory, tissue-reparative M2-like phenotypes. This polarization suppresses immune clearance and promotes an environment conducive to bacterial survival and dissemination. Additional strategies – including biofilm formation, small colony variants, and inhibition of phagolysosomal killing – further enhance persistence and immune evasion. While these …

The Characterization Of Il-27 Production And Its Impact On T Cell Antigen-Specificity And Diversity In A Neonatal Bcg Vaccination Model, Ashley M. Divens

Graduate Theses, Dissertations, and Problem Reports (ETD)

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb), and it has plagued humans for most of recorded history. Despite strong efforts to prevent and treat TB, it remains the leading cause of death due to a pathogen and is most prevalent in certain regions of Asia and Africa. Currently, the only approved vaccine to prevent TB is the live-attenuated Bacillus Calmette-Guérin (BCG) vaccine. Most countries have a universal BCG vaccination policy, but the vaccine ultimately fails to be protective. The BCG vaccine is most effective in children and protects against disseminated TB, but protection wanes 10-15 years after vaccination causing …

5-Fluorouracil Induced Oxidative Stress Is Variable Across Triple Negative Breast Cancer Cell Lines, Rachel L. Walker

Departmental Honors & Graduate Capstone Projects

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with treatment limited to chemotherapy. However, not all patient tumors respond to chemotherapy. The variable cytotoxic effects of chemotherapies may be due to how cancer cells regulate reactive oxygen species (ROS). In this study, we examined two mouse breast cancer cell lines: 4T1 and EO771, vary when treated with hydrogen peroxide (H2O2) and 5-Fluorouracil (5FU), known ROS-inducing substances. In 4T1 cells H2O2 increased oxidized DNA but caused minimal cell death. While in EO771 cells that same amount of H2O2 caused complete apoptosis. Cell number, ROS, and cell death showed …

Review Of The Diagnosis, Pathophysiology, And Treatment Of Naegleria Fowleri-Induced Primary Amoebic Meningoencephalitis, Terrance Zhang

MCB Articles

Naegleria fowleri is a thermophilic, ubiquitous, free-living amoeba, but is also known as the “brain-eating” amoeba. This is the etiological agent of a rare and fulminant waterborne disease known as Primary Amoebic Meningoencephalitis (PAM) that is acutely fatal in 90-99% of reported cases. Those who come into contact with infested waters are at risk of introducing the amoeba into their upper nasal canal, whence the trophozoite form is known to migrate along the olfactory nerve, through the cribriform plate, and enter the central nervous system. Although the exact pathogenesis of N. fowleri is not known, studies have demonstrated contact-dependent and …

Elucidating The Mechanism Of Interleukin-17a Signaling In The Pathogenesis Of West Nile Virus, Farzana Nazneen

Dissertations

West Nile Virus (WNV), a neurotropic flavivirus transmitted by mosquitoes, is a leading cause of viral encephalitis in the United States and remains a significant public health concern. Unfortunately, no vaccine or therapeutic intervention is available against WNV infection. Previous studies, including ours, demonstrated that interleukin-17A (IL-17A) signaling increases the cytotoxic potential of CD8⁺ T cells to facilitate WNV and parasite clearance; however, the molecular mechanism is not understood. IL-17 receptor C (IL-17RC) is an obligatory co-receptor with IL-17 receptor A (IL-17RA) for signaling induced by IL-17A, IL-17A/F, and IL-17F. In this study, we found that IL-17RC deficient ( …

Id1 And Id3 Functions In The Modulation Of The Tumour Immune Microenvironment In Adult Patients With B-Cell Acute Lymphoblastic Leukaemia, Nathaly Poveda-Garavito, Carlos A. Orozco Castaño, Yulieth Torres-Llanos, Nataly Cruz-Rodriguez, Rafael Parra-Medina, Sandra Quijano, Jovanny Zabaleta, Alba Lucia Combita

School of Medicine Faculty Publications

Introduction: B-cell acute lymphoblastic leukemia (B-ALL) in adults often presents a poor prognosis. ID1 and ID3 genes have been identified as predictors of poor response in Colombian adult B-ALL patients, contributing to cancer development. In various cancer models, these genes have been associated with immune regulatory populations within the tumor immune microenvironment (TIME). B-ALL progression alters immune cell composition and the bone marrow (BM) microenvironment, impacting disease progression and therapy response. This study investigates the relationship between ID1 and ID3 expression, TIME dynamics, and immune evasion mechanisms in adult B-ALL patients. Methods: This exploratory study analysed BM samples from 10 …