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The Prevalence Of Cytauxzoon Felis In Southern United States, Anna Haynes May 2025

The Prevalence Of Cytauxzoon Felis In Southern United States, Anna Haynes

Biological Sciences Undergraduate Honors Theses

Cytauxzoonosis, caused by transmission from a tick infected with the pathogen Cytauxzoon felis, is considered an emerging tick-borne disease in domestic felines. While not as fatal in other vertebrates such as the reservoir host Lynx rufus (bobcat), in domestic cats, infection is fatal nearly 100% of the time. This study sought to screen ticks pulled from felines for the pathogen across three states in an area identified as a hotspot. Out of 80 ticks screened, 12 tested positive for the pathogen. The positive population of ticks came from 3 neighboring counties in Southern Missouri: Jasper, McDonald, and Newton. McDonald …


Antimicrobial Peptides Improve Antibiotic-Mediating Killing Of Methicillin-Resistant Staphylococcus Aureus (Mrsa) Biofilms, Alya R. Theriault May 2025

Antimicrobial Peptides Improve Antibiotic-Mediating Killing Of Methicillin-Resistant Staphylococcus Aureus (Mrsa) Biofilms, Alya R. Theriault

All Theses And Dissertations

Staphylococcus aureus can cause drug-resistant, biofilm-associated infections. These infections place methicillin-resistant S. aureus (MRSA) as one of the sixth leading bacterial pathogens associated with deaths due to antimicrobial resistance. Traditional antibiotics are no longer enough to treat these resistant infections and novel therapeutics are needed. Antimicrobial adjuvants are a potential strategy for improving efficacy of existing antibiotics, and antimicrobial peptides (AMPs) may have adjuvant activity. Recent reports showed that AMPs improve antibiotic activity against planktonic staphylococci, but whether AMPs might alter antibiotic efficacy against biofilm-resident staphylococcus is less clear. We tested the effect of nine AMPs on staphylococcal biofilm susceptibility …


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 …


Which Costimulatory Domains In Chimeric Antigen Receptor T Cells Induce Cytokine Responses That Are Linked To A More Toxic Car T Cell Therapy In Acute Lymphocytic Leukemia?, Elisabeth Cohen May 2025

Which Costimulatory Domains In Chimeric Antigen Receptor T Cells Induce Cytokine Responses That Are Linked To A More Toxic Car T Cell Therapy In Acute Lymphocytic Leukemia?, Elisabeth Cohen

Longwood Senior Thesis Proposal

No abstract provided.


Activity Of Novel Ceftibuten-Avibactam, Ceftazidime-Avibactam, And Comparators Against A Challenge Set Of Enterobacterales From Outpatient Centers And Nursing Homes Across The United States (2022–2024), Aliaa Fouad, April M. Bobenchik, Robin Chamberland, Andrew E. Clark, Holly K. Huse, Isabella W. Martin, A. Brian Mochon, Erik Munson, Maroun M. Sfeir, Monica Srodon, Kimberly Taylor, Yungchou Wang, Lars F. Westblade, David P. Nicolau, Tomefa E. Asempa May 2025

Activity Of Novel Ceftibuten-Avibactam, Ceftazidime-Avibactam, And Comparators Against A Challenge Set Of Enterobacterales From Outpatient Centers And Nursing Homes Across The United States (2022–2024), Aliaa Fouad, April M. Bobenchik, Robin Chamberland, Andrew E. Clark, Holly K. Huse, Isabella W. Martin, A. Brian Mochon, Erik Munson, Maroun M. Sfeir, Monica Srodon, Kimberly Taylor, Yungchou Wang, Lars F. Westblade, David P. Nicolau, Tomefa E. Asempa

Clinical Lab Sciences Faculty Research and Publications

Ceftibuten is being developed in combination with the oral prodrug of avibactam. Outpatient isolates (n = 500) from 11 US states underwent susceptibility testing with manual broth microdilution. Ceftibuten had susceptibility rates of 64% (CLSI) and 23% (EUCAST). Ceftibuten-avibactam achieved 96.4% inhibition at MIC ≤ 1 µg/mL. Susceptibility rates were as follows: cefpodoxime (2.6%), ceftriaxone (1%), ceftazidime-avibactam (99.6%), tebipenem (89%), ertapenem (94.4%), levofloxacin (26.6%), trimethoprim-sulfamethoxazole (40.2%), and fosfomycin (96.8%). Ceftibuten-avibactam demonstrates potent in vitro activity against cephalosporin non-susceptible isolates.


Bang!: Real-Time Measurements And Transcriptomics Of Metabolic Reprogramming In Activated Macrophages At Fever Temperature, Kenneth Howard Taylor May 2025

Bang!: Real-Time Measurements And Transcriptomics Of Metabolic Reprogramming In Activated Macrophages At Fever Temperature, Kenneth Howard Taylor

Graduate Theses and Dissertations

We investigated the real-time metabolic rates of activated macrophage cell lines derived from mouse, chicken and rainbow trout. Each species showed a different kinetic signature with metabolic rates accelerating under fever conditions specific to each organism. Upon activation mouse macrophages increased their rate of glycolysis early and then a later reprogramming phase occurred with a dramatic decrease in oxidative phosphorylation (OXPHOS) accompanied by a reciprocal second increase in glycolytic rates. Chicken macrophages showed an initial increase in both glycolytic and OXPHOS rates. The late drop OXPHOS rates also occurred in chicken however there was no reprogramming that occurred as glycolytic …


Dirty Dianthus: A Review Of The Microbotryum-Dianthus Plant Pathogen System., Roxanne Kaaren Hayes May 2025

Dirty Dianthus: A Review Of The Microbotryum-Dianthus Plant Pathogen System., Roxanne Kaaren Hayes

Electronic Theses and Dissertations

Microbotryum dianthorum is a species complex of smut fungi that act as biotrophic plant pathogens of Dianthus flowering plants. This group of pathogenic fungi are situated within a larger group of fungi that act as biotrophic plant pathogens, some of which are responsible for extensive crop loss in our agricultural system. These pathogens are distinct from other Microbotryum species in their ability to infect not only a single host, but multiple hosts. Their unique ability to parasitize several plant hosts may unlock potential clues about the potential for emergent infection disease in crop systems. Previous work has established that these …


Sars-Cov-2 Modulates Pla2g2d/Pgd2 Signaling To Manipulate Host Immune Response To Increase Disease Severity., Dante L. Hamiel May 2025

Sars-Cov-2 Modulates Pla2g2d/Pgd2 Signaling To Manipulate Host Immune Response To Increase Disease Severity., Dante L. Hamiel

Electronic Theses and Dissertations

Background: Previous studies suggested that SARS-CoV-2 infection could cause diverse immune and metabolic dysregulations, although the underlying mechanisms remain poorly understood. In addition, viruses may escape the immune response by modulating cellular metabolism, mitochondria, and protein functions indicating that immune or metabolic components may represent novel targets for anti-viral strategies. However, whether immune and metabolic disorders interact or affect each other waits to be determined. On the other hand, previous investigations identified the critical roles of a cell membrane-bound phospholipase PLA2G2D and its downstream products PGD2 in regulating the metabolism and inflammation in respiratory system. More importantly, …


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 …


The Effect Of Calorie Restriction On Humoral Responses Towards The Influenza Vaccine, Grayson Kobluk May 2025

The Effect Of Calorie Restriction On Humoral Responses Towards The Influenza Vaccine, Grayson Kobluk

Celebrating Scholarship and Creativity Day (2018-)

Calorie restriction (CR) - a reduction in caloric intake without malnutrition - has been widely studied for its impact on lifespan and the onset of age-related diseases. Emerging research indicates that CR also influences immune function, though its effects can vary depending on the degree of restriction, duration, and individual characteristics. This study examined how CR effects vaccine-specific antibody responses following influenza vaccination. Male and female mice were maintained on either a control diet or a calorie-restricted diet and vaccinated with an inactivated influenza virus vaccine. Antibody titers were measured 28 days post-vaccination to evaluate the magnitude of the humoral …


A Multi-Tiered Approach To Improving Vaccination: Adjuvanticity, Alternate Routes Of Delivery, And Science Communication, Haley Agnes Bridgewater May 2025

A Multi-Tiered Approach To Improving Vaccination: Adjuvanticity, Alternate Routes Of Delivery, And Science Communication, Haley Agnes Bridgewater

Boise State University Theses and Dissertations

Vaccines have been used to prevent infectious disease for over 200 years. While they are an incredible way to prevent loss of life, they can be improved upon. Researchers around the globe are working to improve the immune response and ultimately the protection provided by existing and new vaccines. In this dissertation, I investigate three ways to improve vaccine immune responses: using an adjuvant, using a prime-boost intramammary delivery route in cows, and using microneedle delivery route. Cholera toxin (CT) is a bacterial toxin that has a non-toxic B subunit (CTB) used as a vaccine adjuvant. However, little is known …


Phosphatase Activity And Structure Of The Spoiie Protein In Clostridioides Difficile, Kathryn Wootten May 2025

Phosphatase Activity And Structure Of The Spoiie Protein In Clostridioides Difficile, Kathryn Wootten

Biological Sciences Undergraduate Honors Theses

Clostridioides difficile is a major cause of severe gastrointestinal infections and diseases, particularly in healthcare settings. Because of its ability to produce infectious endospores by sporulation, the protein SpoIIE, which is known to play a role in the regulation of this process, is being explored as a potential therapeutic target. In order to gain better insight into the structure and function of this protein, a concentrated and purified sample of the protein must be obtained. The goal of this study was to determine the conditions that would yield the highest amount of SpoIIE. The density of the cultures of bacteria …


Genomic Diversity Of Salmonella Enterica Serotype Braenderup In New York State, Nicole Zac Soligno May 2025

Genomic Diversity Of Salmonella Enterica Serotype Braenderup In New York State, Nicole Zac Soligno

Biological Sciences

The Gram-negative Salmonella enterica (family Enterobacteriaceae) is a common foodborne pathogen mainly isolated from foods of animal origin. Salmonella can be transmitted to humans, causing diverse symptoms, from self-limiting gastrointestinal diseases to more fatal typhoid fever. The young, elderly, and Individuals with weakened immune systems are especially at risk from salmonellosis. Salmonella is a concern to public health and the food industry throughout the world, and its severity depends largely on its serotype, a classification based on the unique combination of surface antigens. In this study, I aimed to elucidate the population structure and antimicrobial resistance determinants of S. enterica …


Serological Evaluation For Leptospirosis On Samples Received By The Connecticut Veterinary Medical Diagnostic Laboratory (Cvmdl), Hayden R. Samuels May 2025

Serological Evaluation For Leptospirosis On Samples Received By The Connecticut Veterinary Medical Diagnostic Laboratory (Cvmdl), Hayden R. Samuels

Honors Scholar Theses

Leptospirosis is a globally distributed zoonotic disease caused by pathogenic species of Leptospira, motile spirochetes capable of infecting humans and animals. Transmission typically occurs through contact with water or soil contaminated by the urine of reservoirs or infected animals. Although leptospirosis is considered a neglected tropical disease, its geographic range is expanding due to climate change and urbanization. Surveillance remains limited in many regions, especially in the United States. This study aimed to assess the seroprevalence and serovar diversity of Leptospira exposure in a variety of domestic and wild animals submitted to the Connecticut Veterinary Medical Diagnostic Laboratory (CVMDL). …


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.


African Sleeping Sickness: From Basic Biology To Future Directions, Riddhi R. Patel May 2025

African Sleeping Sickness: From Basic Biology To Future Directions, Riddhi R. Patel

All Theses

African Sleeping Sickness is a Neglected Tropical Disease (NTD) which poses a significant health risk to impoverished populations in 36 Sub-Saharan African countries. It is a devastating disease caused by the protozoan parasite Trypanosoma brucei, which is transmitted to mammals via the bite of infected tsetse flies. The disease manifests in two stages: the hemolymphatic stage and the meningoencephalitic stage. In the latter stage, it invades the Central Nervous System (CNS) and can be fatal if left untreated. It is caused by morphologically indistinguishable species of Trypanosoma brucei in both humans and animals, where in humans it is known as …


Impact Of Temperature And Microbial Infection On The Honey Bee Hemocytes, Michael E. Oeth May 2025

Impact Of Temperature And Microbial Infection On The Honey Bee Hemocytes, Michael E. Oeth

Master's Theses

Introduction

Honey bees (Apis mellifera) rely on hemocytes for immunity, wound healing, and hemolymph homeostasis. While 32°C reflects optimal hive conditions, suboptimal temperatures (22°C) and stressors like pathogens (Varroa destructor, bacteria) or pesticides impair hemocyte function. Using clodronate liposomes (CLD) to deplete hemocytes, we assessed how immune suppression interacts with these stressors.

Methods

Newly emerged (5-day-old) and older (15-day-old) bees were assigned to: CLD, control liposomes (LP), PBS, injection wound, or no treatment. Cohorts were exposed to 32°C (optimal) or 22°C (stressful for non-immunosuppressed bees). Fifteen-day-old bees were challenged with Escherichia coli or Staphylococcus aureus. Survival, hemolymph volume, and hemocyte …


Network-Based Attacks In Cloud Computing In 2020-2024, Yaswanth Sai Manikanta Anguluri May 2025

Network-Based Attacks In Cloud Computing In 2020-2024, Yaswanth Sai Manikanta Anguluri

Electronic Theses, Projects, and Dissertations

As the use of cloud technologies has increased in the past five years, the number of network attacks is also increasing. During 2020 to 2024, there are lot of changes in cloud technologies which led to various network attacks in the cloud computing environments from 2020 to 2024. This study investigates the evolution of network-based attacks in cloud environments from 2020 to 2024. Data was collected from Kaggle website to analyze the trends of the evolution of network-based attacks. The research questions are: (Q1) How do the trends change in network-based attack from 2020 to 2024 and why? (Q2) Which …


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 …


The Roles Of Rnt1 And Putative Endoribonucleases In Eukaryotic Mrna Degradation, Lee-Ann Notice-Sarpaning May 2025

The Roles Of Rnt1 And Putative Endoribonucleases In Eukaryotic Mrna Degradation, Lee-Ann Notice-Sarpaning

Dissertations and Theses (Open Access)

Endoribonucleases initiate degradation by cleaving RNAs internally. Mutations in these enzymes have been shown to cause diseases such as cancer, developmental disorders, and neurodegenerative diseases. Yet, eukaryotic endoribonucleases have not been well studied, especially with regard to their role in nuclear mRNA degradation. Rnt1 is a Saccharomyces cerevisiae (budding yeast) nuclear endoribonuclease and homolog of human Drosha with well-characterized roles in the processing of ncRNAs. The enzyme recognizes and cleaves double-stranded RNA stems containing a terminal tetraloop with an AGNN consensus sequence. However, the scope and consequence of its function in mRNA degradation has heretofore been unclear. Previous studies have …


Leveraging Innate Immune Sensors To Generate Durable Anti-Glioma Adaptive Immune Responses, Spencer Lea May 2025

Leveraging Innate Immune Sensors To Generate Durable Anti-Glioma Adaptive Immune Responses, Spencer Lea

Dissertations and Theses (Open Access)

Glioblastoma is an aggressive primary brain malignancy harboring a tumor microenvironment that is mostly devoid of T cell effector infiltration but is dominated by immune suppressive microglia, macrophages, and myeloid-derived suppresser cells. These innate immune cells display impaired phagocytosis and antigen presentation and are inadequate for triggering the subsequent immune activating signals needed for anti-tumor adaptive effector responses. Glioblastoma tumors can further restrict phagocytosis and subsequent tumor antigen presentation by the upregulation of the antiphagocytic “don’t eat me” ligand CD47. Here we tested whether activation of multiple conserved innate immune pathways could initiate proinflammatory conversion of suppressive myeloid populations, activation …


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 Veto Activity: Dnam-1-Cd155 Axis In Overcoming Nk Cell-Mediated Allo-Rejection And Applications For Car-T Cell Therapy, Wei-Hsin Liu May 2025

Exploring Veto Activity: Dnam-1-Cd155 Axis In Overcoming Nk Cell-Mediated Allo-Rejection And Applications For Car-T Cell Therapy, Wei-Hsin Liu

Dissertations and Theses (Open Access)

As Miller et al. defined veto activity, it enables cells to target host cytotoxic T lymphocyte (CTL) precursors specific to veto cells' antigens, selectively eliminating anti- donor T cell clones without inducing rejection. By leveraging this unique immune property, two key research aims were proposed: “Exploration of the Impact of Veto Activity on Natural Killer (NK) Cell-Mediated Allo-rejection” and “Development of Off-the- shelf Chimeric Antigen Receptor (CAR)-T Therapy: Engineering Anti-Viral Veto CD8+ T Cells”. As demonstrated in our previous research, in a murine model with mild conditioning, anti-third-party central memory CD8+ veto T cells (veto Tcm) can prevent T cell- …


Harnessing The Immunomodulatory Potential Of Radiofrequency Ablation To Improve Therapeutic Outcomes In Pancreatic Ductal Adenocarcinoma, Bhumi Maniyar May 2025

Harnessing The Immunomodulatory Potential Of Radiofrequency Ablation To Improve Therapeutic Outcomes In Pancreatic Ductal Adenocarcinoma, Bhumi Maniyar

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) continues to rank among the most lethal cancers with poor prognosis. PDAC is characterized by a thick desmoplastic stroma, severe immunological suppression, and resistance tostandard treatments. The need for innovative therapeutic approaches is highlighted by the tumor microenvironment's (TME) critical role in promoting disease development and reducing the effectiveness oftreatment. A promising locoregional treatment that can induce tumor necrosis and modify the TME is endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA). However, there is still minimal understanding around its wider impact on stromal remodeling and immunological activation. This study investigates the immunomodulatory effects of RFA combined with neoadjuvant …


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 …


Stat3, Nf-Κb, And Estrogen Receptor Beta: The Balance Of Inflammation In K-Ras Mutant Lung Adenocarcinoma, Michael J. Clowers May 2025

Stat3, Nf-Κb, And Estrogen Receptor Beta: The Balance Of Inflammation In K-Ras Mutant Lung Adenocarcinoma, Michael J. Clowers

Dissertations and Theses (Open Access)

K-ras mutant lung adenocarcinoma (KM-LUAD) is a difficult-to-treat cancer subtype in which chronic inflammation pervades the tumor immune microenvironment (TIME). Pro-inflammatory pathways dampen the response to treatments, including immune checkpoint inhibitors, necessitating therapies that target this inflammatory signaling network in the TIME. This network is underpinned by interaction and coordination of two inflammatory pathways: signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NF-κB). The balance of these transcription factors determines the degree of anti- vs. pro-tumor immunity, and a skewing towards STAT3 is known to promote tumor development and a pro-tumor TIME. It is also …


Mhc Class I Tyrosine Phosphorylation Site Y320 Augments Cd8+ T Cell Priming, Effector Function, And Memory Response, Yimo Sun, Gregory A Lizee, Yitao Tang, Priscilla Ortiz, R Eric Davis May 2025

Mhc Class I Tyrosine Phosphorylation Site Y320 Augments Cd8+ T Cell Priming, Effector Function, And Memory Response, Yimo Sun, Gregory A Lizee, Yitao Tang, Priscilla Ortiz, R Eric Davis

Dissertations and Theses (Open Access)

The cytoplasmic domain of MHC class I (MHC-I) molecules contains a single, highly conserved tyrosine residue (Y320). In previous work, we found that mice expressing a Y320F-mutated form of H-2Kb had reduced capacity to generate Kb-restricted cytotoxic T lymphocyte (CTL) responses following viral infection, due (at least in part) to defects in endolysosomal trafficking of H-2Kb and antigen cross-presentation by dendritic cells (DCs). In this study, we investigated whether there are additional, post-presentation dependencies on Y320 for T-cell priming. We engineered both human- and mouse-derived antigen-presenting cells (APCs) to express either wild-type MHC-I or variants of …


Investigating Metabolic And Mitochondrial Adaptations Triggered By Blood Flow During The Endothelial-To-Hematopoietic Transition, Paulina Horton May 2025

Investigating Metabolic And Mitochondrial Adaptations Triggered By Blood Flow During The Endothelial-To-Hematopoietic Transition, Paulina Horton

Dissertations and Theses (Open Access)

Hematopoietic stem cell (HSC) transplant is the standard of care for many hematologic diseases. However, many patients cannot benefit from this potentially curative treatment because they cannot find a suitable donor, contributing to a high level of unmet need. Recently, bona fide HSCs capable of robust engraftment and differentiation have been generated from iPSCs utilizing wall shear stress (WSS) to help promote HSC generation. However, the mechanisms through which WSS regulates hematopoiesis remain poorly understood. Scientists, therefore, continue to look for the mechanotransduction pathways that promote hematopoiesis, and key answers may lie in examining the role of extrinsic factors that …


Differential Progression Of Pancreatic Premalignancy In Geographically Distant Murine Transgenic Cohorts Uncovers Key Role Of Microbial Metabolites, Rian M. Howell May 2025

Differential Progression Of Pancreatic Premalignancy In Geographically Distant Murine Transgenic Cohorts Uncovers Key Role Of Microbial Metabolites, Rian M. Howell

Dissertations and Theses (Open Access)

Cancer is a leading cause of death worldwide. Despite recent advances in diagnostic and therapeutic modalities, pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that remains highly lethal. Efforts have been made to increase the understanding of the underlying mechanisms driving early stages of tumor development, when the cancer is most susceptible to intervention. To this end, genetically engineered mouse models (GEMMs) have been developed with the mutations most commonly seen in the patient population. Expression of these mutations in select cellular compartments has resulted in the ability to recapitulate characteristics of human pancreatic cancer such as the development of …