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Full-Text Articles in Immunology and Infectious Disease

Mutation Of Smarca4 Induces Cancer Cell-Intrinsic Defects In The Enhancer Landscape And Resistance To Immunotherapy, Yawen Wang, Ismail M Meraz, Md Qudratullah, Sasikumar Kotagiri, Yanyan Han, Yuanxin Xi, Jing Wang, Kadir C Akdemir, Jack A Roth, Yonathan Lissanu Jun 2025

Mutation Of Smarca4 Induces Cancer Cell-Intrinsic Defects In The Enhancer Landscape And Resistance To Immunotherapy, Yawen Wang, Ismail M Meraz, Md Qudratullah, Sasikumar Kotagiri, Yanyan Han, Yuanxin Xi, Jing Wang, Kadir C Akdemir, Jack A Roth, Yonathan Lissanu

Faculty, Staff and Student Publications

Cancer genomic studies have identified frequent alterations in genes encoding components of the SWI/SNF chromatin remodeling complex, including SMARCA4 and ARID1A. Importantly, clinical reports indicate that SMARCA4-mutant lung cancers respond poorly to immunotherapy and have dismal prognosis. In this study, we corroborated the clinical findings by using immune-humanized, syngeneic, and genetically engineered mouse models of lung cancer harboring SMARCA4 deficiency. Specifically, models with SMARCA4 loss showed decreased response to anti-PD-1 immunotherapy associated with significantly reduced infiltration of dendritic cells and CD4+ T cells into the tumor microenvironment. SMARCA4 loss in tumor cells led to profound downregulation of STING1, IL1β, and …


Monoclonal Antibodies Targeting Candida Disrupt Biofilms And Inhibit Growth Across Global Clinical Isolates, Jonothan Rosario-Colon, Karen Eberle, Hong Xin May 2025

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 …


Chronic Inflammation: The Link Between A High Added Sugar Diet And Disease, Anna Collins May 2025

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 May 2025

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 May 2025

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 Exoy Enzymatic Activity Inhibits Exos-Induced Caspase-3/7 Activation But Not Cytotoxicity In Pmvecs, Connor Holm May 2025

Pseudomonas Aeruginosa Exoy Enzymatic Activity Inhibits Exos-Induced Caspase-3/7 Activation But Not Cytotoxicity In Pmvecs, Connor Holm

Poster Presentations

Pseudomonas aeruginosa (P. aer.) is the most common cause of ventilator associated pneumonia (VAP) in ICU patients. Different combinations of exoenzymes (S, T, Y, and U) are found in P. aer. strains. ExoY is most often associated with VAP in ICU patients. ExoY infection of pulmonary microvascular endothelial cells (PMVECs) induces cell rounding but does not activate intracellular caspase-3/7 or cause cell death. ExoS and ExoT infection of epithelial cells leads to caspase-3/7 dependent cell death. Previous studies using epithelial cells show that ExoY alleviates the cytotoxic effects of ExoS and ExoT. Here, we sought to determine whether ExoY inhibits …


Investigating Fatty Acid Influence On West Nile Virus In Mosquitoes And Birds, Hayley Moree May 2025

Investigating Fatty Acid Influence On West Nile Virus In Mosquitoes And Birds, Hayley Moree

Honors Program: Senior Projects (Public)

Vector-borne diseases, including Zika virus (ZIKV), Dengue virus (DENV), and West Nile virus (WNV), pose considerable global health threats, accounting for over 400 million infections and more than 700,000 deaths annually. Many vector-borne diseases are within the Flaviviridae family. Despite this, effective treatments have not been found for some flaviviruses. Flaviviruses exploit host cellular machinery to facilitate their replication and survival, reprogramming metabolic pathways, including lipid metabolism. Lipids play essential roles in the viral life cycle, providing structural components for the viral envelope, enabling membrane rearrangements for replication complexes, and supplying energy resources necessary for particle assembly.

Targeting lipid metabolism …


Mechanisms Of Behavioral Change In Hosts Of Toxoplasma Gondii: A Review, Olivia Grimsley May 2025

Mechanisms Of Behavioral Change In Hosts Of Toxoplasma Gondii: A Review, Olivia Grimsley

Senior Honors Theses

The parasite Toxoplasma gondii is a highly ubiquitous parasite that latently infects an estimated 33% percent of the global population. Toxoplasmosis is of obvious clinical significance due to the extremely high risks to the unborn who contract it congenitally. Less attention has been given to a more subtle aspect of latent infection, which is the behavioral alterations that are commonly experienced by those who contract the parasite. Infected individuals commonly display a variety of altered behaviors, such as increased aggression and risk-seeking behaviors, depression, higher tendency towards suicide and self-directed violence, a loss of fear response, and a greatly increased …


Epidemiological Inferences Of The Impacts Of Winter Ticks On Moose Health, Krishna S. Woerheide May 2025

Epidemiological Inferences Of The Impacts Of Winter Ticks On Moose Health, Krishna S. Woerheide

Department of Entomology: Dissertations, Theses, and Student Research

The North American Moose (mooz in Anishinaabemowin, Ojibwe language, Alces alces), a culturally significant subsistence species for the Anishinaabe people, faces population decline due to calf predation, pathogen transmission, and parasitism by the winter tick (Dermacentor albipictus), all exacerbated by climate change. This study explores the impact of winter tick infestations on moose health, with a focus on natural mineral seeps as potential transmission hotspots in moose habitats within the Grand Portage Indian Reservation (Gichi Onigaming), on Isle Royale National Park (Minong), and within the 1854 Ceded Territory (greater northeastern Minnesota) - ancestral and present homelands of …


Pseudomonas Aeruginosa Exoenzyme Y Enzymatic Activity Inhibits Exoenzyme S-Induced Caspase Activation But Not Cytotoxicity In Pulmonary Microvascular Endothelial Cells, Connor Holm May 2025

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 …


Fc Gamma Receptors Facilitate Antigenic Modulation Of Lilrb4 And Function As Predictive Biomarkers In Acute Monocytic Leukemia, Joshua Morse May 2025

Fc Gamma Receptors Facilitate Antigenic Modulation Of Lilrb4 And Function As Predictive Biomarkers In Acute Monocytic Leukemia, Joshua Morse

Dissertations and Theses (Open Access)

Acute monocytic leukemia (monocytic AML) is a subtype of AML marked by a proliferation of abnormal monoblasts. This subtype represents approximately 10% of AML cases. The prognosis of monocytic AML is poor, with a 5-year survival of ~30%. Most patients are diagnosed at an age when they are unlikely to survive first-line non-targeted cytotoxic chemotherapy as a bridge to hematopoietic stem cell transplant (HSCT). Even patients who achieve remission commonly relapse. This population of patients would greatly benefit from precision-targeted therapies but currently there are none approved for monocytic AML.

Leukocyte immunoglobulin-like receptor B4 (LILRB4) is an immune checkpoint expressed …


Expanding Inducible Epithelial Resistance Against Pneumonia: Novel Virus, Novel Receptor, Michael Longmire May 2025

Expanding Inducible Epithelial Resistance Against Pneumonia: Novel Virus, Novel Receptor, Michael Longmire

Dissertations and Theses (Open Access)

Pneumonia is the leading infectious cause of death worldwide and presents a continuing risk among immunocompromised patients. Our work has been focused for many years on the phenomenon of inducible epithelial resistance, where activation of the innate immune response in the airway epithelium is necessary and sufficient to produce a pathogen-killing but self-protective environment to prevent severe disease. Inducible resistance is pathogen-agnostic and has been demonstrated against an array of respiratory infections. We achieve this using a combination of pattern recognition receptor agonists – Pam2CSK4 and ODN M362 being the current formulation – which produce synergistic levels of pathogen reduction …


Impact Of Tumor Cell Expressed Cd38 On Metastasis And Immune Evasion In Breast Cancer, Tanvi Visal May 2025

Impact Of Tumor Cell Expressed Cd38 On Metastasis And Immune Evasion In Breast Cancer, Tanvi Visal

Dissertations and Theses (Open Access)

Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer subtype. The epithelial-to-mesenchymal transition (EMT) of cancer cells is a key feature of the metastatic cascade and is not a binary process but often generates malignant cells with both epithelial (E) and mesenchymal (M) traits known as hybrid EM cells. Recent studies highlight the enhanced metastatic potential of the hybrid EM cells. However, molecular insights and targetable vulnerabilities within hybrid EM remain elusive. We discovered that hybrid EM murine tumors are enriched in CD38, an immunesuppressive molecule associated with worse clinical outcomes in liquid malignancies but relatively understudied in solid …


Exploring The Immunologic Consequences Of Atrx Deficiency In Glioma, Benjamin Whitfield May 2025

Exploring The Immunologic Consequences Of Atrx Deficiency In Glioma, Benjamin Whitfield

Dissertations and Theses (Open Access)

ATRX is a key chromatin regulator that is frequently mutated across multiple cancer types. One of the most common ATRX-mutated tumor types is the adult-type glioma, IDH-mutant, Astrocytoma. It is known that ATRX mutation leads to increases in DNA damage, replication stress, and global epigenetic regulation at a cell level; however, less is known about the impact of ATRX mutation on immune signaling. Furthermore, little is known about the interaction of ATRX loss with gain-of-function mutations in IDH. In this paper we set out to explore the impact of ATRX loss on immune signaling in gliomas, both in the context …


Pd-L1 Testing, Treatment Patterns, And Clinical Outcomes Among Patients With Metastatic Nsclc At An Academic Medical Center, 2017-2021, Mehmet Altan, Dawen Sui, Cai Xu, George R Simon, Saliha T Sulihem, Donna Malveaux, Darcy Ponce, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, J Jack Lee, Jianjun Zhang, Don L Gibbons, Ara A Vaporciyan, John V Heymach, Melissa L Santorelli, Thomas Burke, Loretta A Williams May 2025

Pd-L1 Testing, Treatment Patterns, And Clinical Outcomes Among Patients With Metastatic Nsclc At An Academic Medical Center, 2017-2021, Mehmet Altan, Dawen Sui, Cai Xu, George R Simon, Saliha T Sulihem, Donna Malveaux, Darcy Ponce, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, J Jack Lee, Jianjun Zhang, Don L Gibbons, Ara A Vaporciyan, John V Heymach, Melissa L Santorelli, Thomas Burke, Loretta A Williams

Faculty, Staff and Student Publications

Introduction: Targeted therapies and immune checkpoint inhibitors (ICIs) have revolutionized the management of metastatic non-small cell lung cancer (NSCLC) over the past decade.

Methods: This single-center observational study was conducted to describe programmed death-ligand 1 (PD-L1) testing, choice of therapy, and outcomes for adult patients with stage IV NSCLC initiating first-line therapy from 2017 through 2020, with follow-up through June 2021. Patient characteristics and study assessments were described according to four histomolecular subtypes, defined by histologic characteristics and availability of standard-of-care therapies for molecular subgroups at the time of study conduct.

Results: Of 507 eligible patients with metastatic NSCLC, 85 …


Evidence Based Research Review Of Remote Independent Chemotherapy/Immunotherapy Verification, Katrina Perkins, Hannah Holder, Marie St. Clair May 2025

Evidence Based Research Review Of Remote Independent Chemotherapy/Immunotherapy Verification, Katrina Perkins, Hannah Holder, Marie St. Clair

Covenant Nurses Week 2025

No abstract provided.


Intratumoral Fibrin As A Novel Immunomodulatory Factor In Pancreatic Ductal Adenocarcinoma, Mazharul Karim May 2025

Intratumoral Fibrin As A Novel Immunomodulatory Factor In Pancreatic Ductal Adenocarcinoma, Mazharul Karim

Open Access Theses & Dissertations

In-situ coagulation is a common clinical feature of pancreatic ductal adenocarcinoma (PDAC) that presents a highly thrombotic and crosslinked insoluble fibrin (x-fibrin)-laden tumor stroma (FibTS). However, the specific impact of FibTS on immune cells behavior remains largely unexplored in this poorly infiltrated tumor. We aimed to elucidate how FibTS in PDAC regulates immune cell infiltration, polarization, and crosstalk that favors immunosuppressive microenvironment and tumor growth. We characterized human PDAC tissues by multiplex immunostaining and checked the spatial distribution of immune cells based on the presence of x-fibrin. We investigated how FibTS influences the infiltration of tumor-associated macrophage (TAM) and T-cell …


Natural Killer T Cell-Mediated Control Of Francisella Tularensis-Induced Cytokine Storm Syndrome, Cameron M. Torres May 2025

Natural Killer T Cell-Mediated Control Of Francisella Tularensis-Induced Cytokine Storm Syndrome, Cameron M. Torres

Open Access Theses & Dissertations

Inflammation is critical for the effective clearance of viral and bacterial challenges, while simultaneously a mechanism utilized by many highly infectious pathogens to cause disease. The bacterium Francisella tularensis, the causative agent of human tularemia, elicits a cytokine storm, wherein the immune system over-responds to the presence of the bacterium causing a dysregulated release of proinflammatory and regulatory cytokines. Without treatment, tularemia mortality can be as high as 30%, with inhalation of as few as 10 CFUs inducing respiratory tularemia. Natural Killer T (NKT) cells are innate-like T lymphocytes with a diverse array of regulatory functions. Unlike conventional T cells, …


Investigating Genetic Regulators Of Crystal Cell Development In Drosophila Melanogaster, Andrea Feria, Nyla Walbrook, Anisa Turaeva, Rebecca Spokony Apr 2025

Investigating Genetic Regulators Of Crystal Cell Development In Drosophila Melanogaster, Andrea Feria, Nyla Walbrook, Anisa Turaeva, Rebecca Spokony

Publications and Research

Crystal cells, a subset of Drosophila melanogaster hemocytes, are important for melanization, a crucial immune response. While the genetic regulation of crystal cell develop remains incompletely understood, this study investigates the functions of five candidate genes: ACXB, ACXA, Gp210, CG4390, and Cyp4s3; identidied through previous genome-wide association studies. Using the Gal4/UAS system along with RNA interference (RNAi), we exclusively knocked down each gene in third instar larvae and quantified crystal cell populations following heat shock-induced melanization. Our results imply that the knockdown of ACXB and ACXA significantly increased crystal cell counts in both sexes, suggesting these genes either act as …


Evolution Of The Tumor Immune Landscape During Treatment With Tebentafusp, A T Cell Receptor-Cd3 Bispecific, Joseph Sacco, Peter Kirk, Emma Leach, Alexander Shoushtari, Richard Carvajal, Camille Britton-Rivet, Sophie Khakoo, Laura Collins, Luis De La Cruz-Merino, Zeynep Eroglu, Alexandra Ikeguchi, Paul Nathan, Omid Hamid, Marcus Butler, Sarah Stanhope, Koustubh Ranade, Takami Sato Apr 2025

Evolution Of The Tumor Immune Landscape During Treatment With Tebentafusp, A T Cell Receptor-Cd3 Bispecific, Joseph Sacco, Peter Kirk, Emma Leach, Alexander Shoushtari, Richard Carvajal, Camille Britton-Rivet, Sophie Khakoo, Laura Collins, Luis De La Cruz-Merino, Zeynep Eroglu, Alexandra Ikeguchi, Paul Nathan, Omid Hamid, Marcus Butler, Sarah Stanhope, Koustubh Ranade, Takami Sato

Department of Medical Oncology Faculty Papers

Metastatic uveal melanoma is an aggressive disease with poor outcome, which is refractory to immune checkpoint inhibitors. A T cell receptor (TCR)-based CD3 bispecific, tebentafusp, delivers clinical benefit in patients with metastatic uveal melanoma. Understanding the molecular basis for the anti-tumor activity of tebentafusp in an indication where checkpoint inhibitors are ineffective could aid in identification of other solid tumor indications where CD3 bispecifics may serve an unmet need. By analyzing tumor biopsies taken prior to treatment, early on-treatment, and at progression (NCT02570308), using RNA sequencing (RNA-seq) and immunohistochemistry (IHC), we show that expression of interferon-related genes in the tumor …


Does A Waiting Room Increase Same-Day Treatment For Sexually Transmitted Infections Among Pregnant Women? A Quality Improvement Study At South African Primary Healthcare Facilities, Ranjana M. Gigi, Mandisa M. Mdingi, Lukas Bütikofer, Chibuzor M. Babalola, Jeffrey D. Klausner, Andrew Medina-Marino, Christina A. Muzny, Christopher M. Taylor, Janneke H. Van De Wijgert, Remco P. Peters, Nicola Low Apr 2025

Does A Waiting Room Increase Same-Day Treatment For Sexually Transmitted Infections Among Pregnant Women? A Quality Improvement Study At South African Primary Healthcare Facilities, Ranjana M. Gigi, Mandisa M. Mdingi, Lukas Bütikofer, Chibuzor M. Babalola, Jeffrey D. Klausner, Andrew Medina-Marino, Christina A. Muzny, Christopher M. Taylor, Janneke H. Van De Wijgert, Remco P. Peters, Nicola Low

School of Medicine Faculty Publications

BACKGROUND: Same-day testing and treatment of curable sexually transmitted infections (STI) is a strategy to reduce infection duration and onward transmission. South African primary healthcare facilities often lack sufficient waiting spaces. This study aimed to assess the proportion of, and factors influencing, pregnant women waiting for on-site STI test results before and after the installation of clinic-based waiting rooms. METHODS: We conducted an observational quality improvement study at 5 public primary healthcare facilities in South Africa from March 2021 to May 2023. The intervention was the installation of a waiting room in two clinics. Three clinics were used as comparators: …


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 Apr 2025

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 …


Soluble Cd13 Is A Potential Mediator Of Neutrophil-Induced Thrombogenic Inflammation In Sars-Cov-2 Infection, Pei-Suen Tsou, Ramadan A. Ali, Chenyang Lu, Gautam Sule, Carmelo Carmona-Rivera, Serena Lucotti, Yuzo Ikari, Qi Wu, Phillip L. Campbell, Mikel Gurrea-Rubio, Kohei Maeda, Sharon E. Fox, William D. Brodie, Megan N. Mattichak, Caroline Foster, Ajay Tambralli, Srilakshmi Yalavarthi, M Asif Amin, Katarina Kmetova, Bruna Mazetto Fonseca, Emily Chong, Yu Zuo, Michael D. Maile, Luisa Imberti, Arnaldo Caruso, Francesca Caccuri, Virginia Quaresima, Alessandra Sottini, Douglas B. Kuhns, Et Al Apr 2025

Soluble Cd13 Is A Potential Mediator Of Neutrophil-Induced Thrombogenic Inflammation In Sars-Cov-2 Infection, Pei-Suen Tsou, Ramadan A. Ali, Chenyang Lu, Gautam Sule, Carmelo Carmona-Rivera, Serena Lucotti, Yuzo Ikari, Qi Wu, Phillip L. Campbell, Mikel Gurrea-Rubio, Kohei Maeda, Sharon E. Fox, William D. Brodie, Megan N. Mattichak, Caroline Foster, Ajay Tambralli, Srilakshmi Yalavarthi, M Asif Amin, Katarina Kmetova, Bruna Mazetto Fonseca, Emily Chong, Yu Zuo, Michael D. Maile, Luisa Imberti, Arnaldo Caruso, Francesca Caccuri, Virginia Quaresima, Alessandra Sottini, Douglas B. Kuhns, Et Al

School of Medicine Faculty Publications

The soluble variant of the ectopeptidase CD13 (sCD13), released from the cell surface by matrix metalloproteinase 14 (MMP14), is a potent pro-inflammatory mediator, displaying chemotactic, angiogenic, and arthritogenic properties through bradykinin receptor B1 (B1R). We revealed a link between sCD13 and amplified neutrophil-mediated inflammatory responses in SARS-CoV-2 infection. sCD13 was markedly elevated in patients with COVID-19 and correlated with disease severity and variants, ethnicity, inflammation markers, and neutrophil extracellular trap formation (NETosis). Neutrophils treated with sCD13 showed heightened NETosis and chemotaxis, which were inhibited by sCD13 receptor blockade. Meanwhile sCD13 did not induce platelet aggregation. Single-cell analysis of COVID-19 lungs …


Ccr7 Regulated Mechanisms That Limit The Adaptive Immune Response, Jaisel Amilcar Cervantes Apr 2025

Ccr7 Regulated Mechanisms That Limit The Adaptive Immune Response, Jaisel Amilcar Cervantes

Open Access Theses & Dissertations

C-C chemokine receptor 7 (CCR7) is critical in guiding T cell migration within the thymus and peripheral lymphoid tissues, shaping the adaptive immune response by promoting central tolerance and regulating immune homeostasis. Although its role in lymphocyte trafficking is well established, the molecular mechanisms by which CCR7 influences thymocyte development and T cell receptor (TCR) repertoire formation remain less understood. This study examines how CCR7 deficiency impacts thymic selection, TCR diversity, and the signaling events that shape repertoire restriction. Using a homozygously deleted CCR7 murine model, we found that the absence of CCR7 results in a less restricted TCR repertoire …


Assessing Cancer Therapeutic Efficacy In Vivo Using [2h7]Glucose Deuterium Metabolic Imaging, Mario C Chang, Vinay R Malut, Rohit Mahar, Anna Rushin, Marc A Mcleod, Geraldine L Pierre, Indu R Malut, Stephen J Staklinski, Max E Glanz, Mukundan Ragavan, Gaurav Sharma, Manoj Madheswaran, Arshee Badar, Aparna D Rao, Brian K Law, Michael S Kilberg, James H P Collins, Vikram D Kodibagkar, James A Bankson, Ralph J Deberardinis, Matthew E Merritt Mar 2025

Assessing Cancer Therapeutic Efficacy In Vivo Using [2h7]Glucose Deuterium Metabolic Imaging, Mario C Chang, Vinay R Malut, Rohit Mahar, Anna Rushin, Marc A Mcleod, Geraldine L Pierre, Indu R Malut, Stephen J Staklinski, Max E Glanz, Mukundan Ragavan, Gaurav Sharma, Manoj Madheswaran, Arshee Badar, Aparna D Rao, Brian K Law, Michael S Kilberg, James H P Collins, Vikram D Kodibagkar, James A Bankson, Ralph J Deberardinis, Matthew E Merritt

Faculty, Staff and Student Publications

Metabolic imaging produces powerful visual assessments of organ function in vivo. Current techniques can be improved by safely increasing metabolic contrast. The gold standard, 2-[18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging, is limited by radioactive exposure and sparse assessment of metabolism beyond glucose uptake and retention. Deuterium magnetic resonance imaging (DMRI) with [6,6-2H2]glucose is nonradioactive, achieves tumor metabolic contrast, but can be improved by enriched contrast from deuterated water (HDO) based imaging. Here, we developed a DMRI protocol employing [2H7]glucose. Imaging 2H-signal and measuring HDO production in tumor-bearing mice detected differential glucose utilization across baseline tumors, tumors treated with vehicle control or …


The Design, Construction, And Testing Of Mrna Vaccine Against Equine Herpes Virus, Bhawana Devkota Mar 2025

The Design, Construction, And Testing Of Mrna Vaccine Against Equine Herpes Virus, Bhawana Devkota

LSU Master's Theses

Equine Herpesvirus-1 (EHV 1) is a worldwide significant pathogen that causes respiratory illness, abortion, and neurological disorders in equine. Current vaccines, including live attenuated, inactivated, and subunit platforms, do not prevent viral latency, mucosal shedding, or cross-strain immunity, requiring alternative approaches. To address these gaps, this project explores the design, synthesis, and in vitro testing of an mRNA vaccine targeting immunogenic EHV 1 glycoprotein (gB, gC, gD, gG, and gM). Epitopes were computationally predicted using the Immune Epitope Database (IEDB), codon-optimized for Bos taurus, and cloned into pUCIDT vectors using SP6/T7 promoters. In vitro transcription (IVT) used nucleotide modifications …


Strategies To Improve Antibody-Mediated Protection Against Herpes Simplex Virus Infections, Matthew D. Slein Mar 2025

Strategies To Improve Antibody-Mediated Protection Against Herpes Simplex Virus Infections, Matthew D. Slein

Dartmouth College Ph.D Dissertations

No efficacious vaccine exists for herpes simplex virus and the global burden of disease remains high. Antibodies can serve as potent therapeutics to protect high risk populations such as neonates. Although rare, neonatal HSV (nHSV) infections can result in significant mortality and lifelong neurological morbidity even with antiviral therapy. While HSV-specific maternally derived antibodies significantly reduce the risk of neonatal disease in humans, the mechanisms by which they mediate protection have yet to be described. Using a mouse model of neonatal HSV (nHSV) infections we aimed to determine the mechanisms of antibody-mediated protection using monoclonal antibodies (mAbs) targeting two of …


Confounding Factors Of Cervical Carcinogenesis And Cervical Cancer Health Disparity, Vivek Kumar Kashyap, Namita Sinha, Nadeem Zafar, Murali M. Yallapu, Santosh Kumar, Everardo Cobos, Subhash C. Chauhan Mar 2025

Confounding Factors Of Cervical Carcinogenesis And Cervical Cancer Health Disparity, Vivek Kumar Kashyap, Namita Sinha, Nadeem Zafar, Murali M. Yallapu, Santosh Kumar, Everardo Cobos, Subhash C. Chauhan

Research Symposium

Clinical studies show that cervical cancer is the most frequently detected cancer in women living with human immunodeficiency virus (HIV), which has been defined as an acquired immunodeficiency syndrome (AIDS). Women living with HIV are 6 times more likely to develop cervical cancer compared to the general population, and an estimated 5% of all cervical cancer cases are attributable to HIV. Studies suggest that several genes are involved in different molecular pathways, which can influence the vulnerability, severity, or advancement of cervical cancer in the presence of HIV and human papillomavirus (HPV) co-infection. Clinical studies have also shown levels of …


Hiv And Bacterial Lps Synergistically Activate Aim2 Inflammasome In Primary Human Oral Keratinocytes, Md Shafayat Jamil, Deepa Roy, Upal Roy, Hansapani Rodrigo, Nirakar Sahoo, Chun Xu Mar 2025

Hiv And Bacterial Lps Synergistically Activate Aim2 Inflammasome In Primary Human Oral Keratinocytes, Md Shafayat Jamil, Deepa Roy, Upal Roy, Hansapani Rodrigo, Nirakar Sahoo, Chun Xu

Research Symposium

Background: HIV infection profoundly disrupts the oral microbiome, increasing the presence of Gram-negative bacteria such as Porphyromonas gingivalis (P. gingivalis), which is detected in over 80% of cases. P. gingivalis secretes lipopolysaccharide (LPS), a potent immune stimulant that can damage primary human oral keratinocytes (HOK) even in antiretroviral therapy (cART) treated people with HIV (PWH). HOK cells respond to bacterial and viral stimuli by activating inflammasome complexes, including AIM2, a DNA-sensing inflammasome protein. While LPS alone is known to trigger canonical and non-canonical pathways, leading to inflammasome activation, our study investigates how HIV exposure synergizes with LPS to induce the …


Development Of A Multi-Epitope Peptide Vaccine Against Monkeypox Virus: Immunoinformatics Analysis For South East Asian Hla Alleles, Nelson Chandra, Mochammad Aqilah Herdiansyah, Viol Dhea Kharisma, Arif Nur Muhammad Ansori, Arli Aditya Parikesit Mar 2025

Development Of A Multi-Epitope Peptide Vaccine Against Monkeypox Virus: Immunoinformatics Analysis For South East Asian Hla Alleles, Nelson Chandra, Mochammad Aqilah Herdiansyah, Viol Dhea Kharisma, Arif Nur Muhammad Ansori, Arli Aditya Parikesit

Makara Journal of Science

The monkeypox virus (MPXV), a DNA virus causing zoonotic disease, poses major global public health challenges, with mortality rates between 3%–6%. Although smallpox vaccines provide partial cross-protection, there is a critical need for a dedicated, effective monkeypox (mpox) vaccine. This study aimed to design a multi-epitope peptide-based vaccine specifically adapted to the HLA allele profiles common in Southeast Asian populations, where MPXV cases are rising. Using immunoinformatics, we screened for and detected B and T cell epitopes from the MPXV cell surface antigen and IFN-alpha/beta receptor proteins. The vaccine design was validated through a rigorous evaluation of its antigenicity, immunogenicity, …