Immunology and Infectious Disease Commons^™

Murine Studies On Ketogenic Modulation Of Metabolism And Epigenetics In Olfaction- Based Learning, Lps Inflammatory Response, And Sex Dimorphisms In Dietary Response, Sara E. H. Moss

USF Tampa Graduate Theses and Dissertations

Ketogenic diets are well-established therapeutic interventions for epilepsy, with documented neuroprotective effects arising from their metabolic, antioxidant and anti-inflammatory properties. Beyond epilepsy, ketogenic therapies are under investigation for various conditions including Alzheimer disease, cancer, diabetes, and cardiovascular disease. These diets suppress insulin levels and shift metabolic physiology toward fat and ketone body metabolism. This elevates circulating levels of ketone bodies, namely beta-hydroxybutyrate, acetoacetate, and acetone, which serve as both energy substrates and signaling molecules. The state of elevated ketone bodies (ketosis) can be achieved with various formulations of a ketogenic diet as well as exogenous ketone supplementation, though the signaling …

Barriers To Engagement Of Care For Patients Presenting With Comorbid Human Immunodeficiency Virus (Hiv) And Major Depression Or Anxiety Disorder Diagnoses, Rachel C. V. Kingsley

USF Tampa Graduate Theses and Dissertations

Despite significant global advancements in HIV care, engagement in continuous HIV care remains a challenge, particularly for individuals living with comorbid HIV and mental health disorders. This dissertation examines the barriers to continuous HIV care for those individuals living with comorbid HIV and depression and/or anxiety in the Tampa Bay area. This dissertation argues that dual health challenges are dually challenging. This study highlights how structural vulnerabilities, how feelings of inclusion and exclusion impact engagement in care, and socioeconomic challenges intersect to shape patient experiences and impact adherence to treatment. Drawing on critical medical anthropology, structural violence, embodied belonging, and …

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

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

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

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

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, …

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, …

Chimeric Cd40 Polypeptides And Methods Of Use In Immunotherapy, Eric Tran, Myungkyu Jang, Timothy A Erickson

Technology Transfer - Patents

No abstract provided.

Mechanisms Of Macrophage Metabolic Activation And Paracrine Wnt Signaling In The Pathogenesis Of Systemic Sclerosis, Emily Ann Morris

Dartmouth College Ph.D Dissertations

Systemic sclerosis (SSc) is a chronic autoimmune disease of unknown etiology. We have previously shown that macrophages (MØs) play a critical role in its pathogenesis; however, the mechanisms driving MØ activation in SSc remain poorly understood. This dissertation investigates the molecular signaling pathways and biochemical mechanisms underlying profibrotic MØ activity in SSc.

First, I identify a novel MØ-specific effect of mycophenolate mofetil (MMF), the standard-of-care treatment for SSc. While MMF is a well characterized lymphostatic, my findings demonstrate that its active metabolite, mycophenolic acid (MPA), is also capable of directly inhibiting myeloid viability and profibrotic MØ activation by suppressing de …

Immunological Biomarkers Of Response And Resistance To Treatment With Cabozantinib And Nivolumab In Recurrent Endometrial Cancer, Vladimir Roudko, Diane Marie Del Valle, Emir Radkevich, Geoffrey Kelly, Xie Hui, Manishkumar Patel, Edgar Gonzalez-Kozlova, Kevin Tuballes, Howard Streicher, Swati Atale, Lisa Wang, Benito Czinczin, Seunghee Kim-Schulze, Ignacio I Wistuba, Cara L Haymaker, Gheath Al-Atrash, Ganiraju Manyam, Jianjun Zhang, Ryan Thompson, Mayte Suarez-Farinas, Stephanie Lheureux, Sacha Gnjatic

Faculty, Staff and Student Publications

Background: Antiangiogenics combined with immune checkpoint blockade have become standard of care for recurrent endometrial cancer after standard platinum-based chemotherapy. To dissect mechanisms and define biomarkers associated with clinical outcomes to these combinations, we applied multidimensional immune monitoring to peripheral blood specimens collected from a randomized phase 2 trial of nivolumab with or without cabozantinib in 75 evaluable patients with recurrent endometrial cancer (NCI ETCTN 10104, NCT03367741). This trial demonstrated superiority of the combination to nivolumab alone.

Methods and results: Using Olink proteomics, mass cytometry, tumor antigen-specific ELISA, and whole exome tumor sequencing, we identified longitudinal immune signatures specific …

Survey Of Mosquito Larval Habitats At The Ksu Field Station, Rose Sofia, Eli Lovvorn, Aspen Hartman, Andrew Haddow

Symposium of Student Scholars

The greater Atlanta metropolitan area hosts numerous mosquito species that are nuisance biters and can transmit arthropod-borne diseases to humans. We surveyed the Kennesaw State University (KSU) Field Station – an incredibly biodiverse location – where student, staff, and faculty-led groups engage in outdoor research and teaching activities. The KSU Field Station located in Cobb County, GA is a heavily trafficked 25-acre property that may attract various mosquito species capable of transmitting pathogens to humans and animals alike. On August 27th, 2024, our team investigated the KSU Field Station to quantify and record potential water-holding containers that serve as mosquito …

How Hormonal Changes And The Oral Microbiome Interact With Periodontal And Alzheimer’S Disease To Influence Chronic Inflammation And Cognitive Decline?, Vanessa Chavez-Sinks, Kamran H. Awan

Annual Research Symposium

This review aims to investigate the potential of the bidirectional relationship between Alzheimer’s disease and periodontal disease. The Key players of hormonal fluctuations and microbiome dysbiosis emphasize the shared mechanisms that interplay among both conditions to identify the potential therapeutic opportunities.

Inhibition Of Histone Methyltransferase Ezh2 For Immune Interception Of Colorectal Cancer In Lynch Syndrome, Charles M Bowen, Fahriye Duzagac, Abel Martel-Martel, Laura Reyes-Uribe, Mahira Zaheer, Jacklyn Thompson, Nan Deng, Ria Sinha, Soham Mazumdar, Melissa W Taggart, Abhinav K Jain, Elena Tosti, Winfried Edelmann, Krishna M Sinha, Eduardo Vilar

Faculty, Staff and Student Publications

Colorectal precancers in Lynch syndrome (LS) exhibit a distinct immune profile, presenting unique opportunities for developing immune-interception strategies to prevent carcinogenesis. Epigenetic modulation by EZH2 of immune-related genes is implicated in the carcinogenesis of different cancer types, including colorectal cancer. This study utilizes a mouse model of LS and ex vivo colonic organoids to assess the effects of the EZH2 inhibitor GSK503 on immune regulatory pathways, tumorigenesis, and epigenetic reprogramming. Our findings revealed that GSK503 significantly increased CD4+ and CD8+ T cells in both splenocytes and colonic mucosa of treated mice compared with controls. Additionally, a preventive dose of GSK503 …

Comprehensive Sumo Proteomic Analyses Identify Hiv Latency-Associated Proteins In Microglia., Fergan Imbert, Dianne Langford

Rowan-Virtua School of Osteopathic Medicine Departmental Research

SUMOylation, the post-translational modification of proteins by small ubiquitin-like modifiers, plays a critical role in regulating various cellular processes, including innate immunity. This modification is essential for modulating immune responses and influencing signaling pathways that govern the activation and function of immune cells. Recent studies suggest that SUMOylation also contributes to the pathophysiology of central nervous system (CNS) viral infections, where it contributes to the host response and viral replication dynamics. Here, we explore the multifaceted role of SUMOylation in innate immune signaling and its implications for viral infections within the CNS. Notably, we present novel proteomic analyses aimed at …

Single Amino Acid Changes Impact The Ability Of Drosophila Melanogaster Cecropins To Inhibit Growth Of Providencia Pathogens, Sarah Smith, Marla Forfar, Christopher Feudale, Lauren Shaffer, Grace Ginder, Marion Duval, Quinn Smith, Moria C. Chambers

Faculty Journal Articles

As antibiotic-resistant bacteria spread worldwide, the need to develop novel antimicrobial agents is urgent. One rich source of potential antimicrobials is the insect immune system, as insects produce a wide range of antimicrobial peptides (AMPs) with diverse sequences and structures. Insects also encounter many bacterial pathogens, some of which are closely related to pathogens of clinical relevance. However, despite interest in AMPs as therapeutics, the relationships between the amino acid sequence, biophysical properties, antimicrobial activity, and specificity are still not generalizable. To improve our understanding of these relationships, we assessed how single amino acid changes in cecropin AMPs produced by …

Characterizing Malaria Infections In Caribbean Lizards: Parasite Niche Expansion & Host Response, Sarah J. Pangburn

Dissertations, Theses, and Capstone Projects

Malaria is historically one of the most severe parasitic human diseases and is still responsible for over half a million deaths annually. Plasmodium species, the causative agents of malaria, are often characterized by two hallmark features of their asexual stages: the invasion of vertebrate red blood cells and the presence of hemozoin pigment as a byproduct of host hemoglobin digestion. Despite their evolutionary relatedness to mammalian Plasmodium, wildlife malaria parasites are understudied, leaving their vast genetic diversity to be explored. Lizard-infective malaria parasites, for example, include over 100 species of Plasmodium and present a diverse array of phenotypes, some …

The Role Of Gsk-3Α Inhibition In Attenuating Lps-Induced Inflammation In Raw 264.7 Cells, Oluwaseyi Oyewole

Theses and Dissertations

Glycogen synthase kinase-3 (GSK-3), an enzyme that modulates glucose metabolism, has been recognized as an essential target in major inflammatory diseases based on its great specificity in substrate recognition. GSK-3β has been connected to cancer, obesity, liver diseases, and neurological diseases. Nonetheless, the other GSK-3 isoform, GSK-3α, is much less studied. Previous studies from our laboratory showed that inhibiting GSK-3α potentially confers an anti-inflammatory response when tested on microglia. However, little has been documented regarding the exact mechanism by which GSK-3α exerts its effect. One of the potential mechanisms involving its anti-inflammatory effect could be partially attributed to activating the …

Immuno-Bioinformatics Study Of Secondary Metabolites From Watercress Nasturtium Officinale As Immunostimulant In Whiteleg Shrimp Litopenaeus Vannamei By Targeting Peroxinectin And Scavenger Receptor Class B, Qurrota A’Yunin, Muhaimin Rifa’I, Maftuch Maftuch, Yoga Dwi Jatmiko, Muhammad Hermawan Widyananda, Triyanto Triyanto, Muhammad Tegar Handrianto

Karbala International Journal of Modern Science

The viral disease affects the whiteleg shrimp (Litopenaeus vannamei) and causes losses. Immunostimulants are recognized as a more environmentally friendly approach to disease management and antimicrobial properties of aquatic organisms. Watercress (Nasturtium officinale) is an aquatic plant species that contains antioxidant properties that can protect the organism from disease and boost the immune system. Shrimp rely heavily on innate immunity to combat infectious agents due to their absence of adaptive immunity. Peroxinectin and scavenger receptor class B (SRB) play essential roles in the shrimp defense system. This research employs a bioinformatic to assess the immunostimulatory potential …

Urine Proteomics Defines An Immune Checkpoint-Associated Nephritis Signature, James P Long, Shailbala Singh, Yanlan Dong, Cassian Yee, Jamie S Lin

Faculty, Staff and Student Publications

Immune checkpoint inhibitor (ICI) therapy is a cornerstone treatment for many cancers, but it can induce severe immunotoxicity, including acute interstitial nephritis (AIN). Currently, kidney biopsy is required to differentiate ICI-AIN from other causes of acute kidney injury (AKI). However, this invasive approach can lead to morbidity, delayed glucocorticoid treatment for patients with AIN, and unnecessarily prolonged suspension of ICI therapy in non-AIN patients. Delayed or incorrect diagnosis of ICI-AIN is particularly detrimental, as over 50% of patients are at risk of permanent renal damage. Thus, there is an urgent need for non-invasive biomarkers that can rapidly and accurately distinguish …