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Plant Model Of Α-Synucleinopathy: Expression Of Α-Synuclein A53t Variant In Hairy Root Cultures Leads To Proteostatic Stress And Dysregulation Of Iron Metabolism, Jasmina Kurepa, Kristen A. Bruce, Greg A. Gerhardt, Jan A. Smalle May 2024

Plant Model Of Α-Synucleinopathy: Expression Of Α-Synuclein A53t Variant In Hairy Root Cultures Leads To Proteostatic Stress And Dysregulation Of Iron Metabolism, Jasmina Kurepa, Kristen A. Bruce, Greg A. Gerhardt, Jan A. Smalle

Neurology Faculty Publications

Synucleinopathies, typified by Parkinson’s disease (PD), entail the accumulation of α- synuclein (αSyn) aggregates in nerve cells. Various αSyn mutants, including the αSyn A53T variant linked to early-onset PD, increase the propensity for αSyn aggregate formation. In addition to disrupting protein homeostasis and inducing proteostatic stress, the aggregation of αSyn in PD is associated with an imbalance in iron metabolism, which increases the generation of reactive oxygen species and causes oxidative stress. This study explored the impact of αSyn A53T expression in transgenic hairy roots of four medicinal plants (Lobelia cardinalis, Artemisia annua, Salvia miltiorrhiza, and Polygonum multiflorum). In all …


Introduction Of The Anatomy Academy Program To Children In A Rural Elementary School, Rox Aurelio, Madison Dobbs, Nicole Horn, Gianni Terrana May 2024

Introduction Of The Anatomy Academy Program To Children In A Rural Elementary School, Rox Aurelio, Madison Dobbs, Nicole Horn, Gianni Terrana

UNLV Theses, Dissertations, Professional Papers, and Capstones

Children in rural communities experience health and education disparities. Early exposure to health promoting habits can positively impact future health habits. Healthcare providers who grew up in rural areas are more likely to practice in rural areas. Doctor of physical therapy students and physical therapists implemented Anatomy Academy, a service-learning program aimed at promoting healthy living and introducing healthcare occupations, to elementary students in a rural area as this program had previously only been implemented in urban areas. The Biomedical Institutional Review Board at the University of Nevada, Las Vegas approved this study. A 40-minute lesson was delivered weekly for …


Vitamin D Regulates Covid-19 Associated Severity By Suppressing The Nlrp3 Inflammasome Pathway, Bariaa Khalil, Narjes Saheb Sharif-Askari, Shirin Hafezi, Fatemeh Saheb Sharif-Askari, Fatme Al Anouti, Qutayba Hamid, Rabih Halwani May 2024

Vitamin D Regulates Covid-19 Associated Severity By Suppressing The Nlrp3 Inflammasome Pathway, Bariaa Khalil, Narjes Saheb Sharif-Askari, Shirin Hafezi, Fatemeh Saheb Sharif-Askari, Fatme Al Anouti, Qutayba Hamid, Rabih Halwani

All Works

Background The role of vitamin D3 (VitD3) in modulating innate and adaptive immunity has been reported in different disease contexts. Since the start of the coronavirus disease-2019 (COVID-19) pandemic, the role of VitD3 has been highlighted in many correlational and observational studies. However, the exact mechanisms of action are not well identified. One of the mechanisms via which VitD3 modulates innate immunity is by regulating the NLRP3-inflammasome pathway, being a main underlying cause of SARS-CoV-2-induced hyperinflammation. Aims and main methods Blood specimens of severe COVID-19 patients with or without VitD3 treatment were collected during their stay in the intensive care …


Implementing The Edinburgh Postnatal Depression Scale In The Emergency Department And Family Care Settings, Laura Hardiek, Thomas Dissette May 2024

Implementing The Edinburgh Postnatal Depression Scale In The Emergency Department And Family Care Settings, Laura Hardiek, Thomas Dissette

Doctor of Nursing Practice Projects

Postpartum depression affects approximately 10% to 20% of patients who have given birth in the year prior and can detrimentally affect maternal-child relationships. Postpartum depression (PPD) is a mood disorder following birth, whereas postpartum psychosis (PPP) is a severe mental illness and a medical emergency. If untreated, both disorders can have long-term harmful effects on mothers, infants, and families. Utilizing screening tools, providers can identify these disorders in applicable patients. The Edinburgh Postnatal Depression Scale (EPDS) is an effective method of recognizing patients most at risk, with a positive score of >/=10 indicating the likelihood of depression. [SB1] The purpose …


Pneumococcal And Influenza Vaccine Co-Administration In The Incarcerated Population, Kaitlyn Stroh May 2024

Pneumococcal And Influenza Vaccine Co-Administration In The Incarcerated Population, Kaitlyn Stroh

Doctor of Nursing Practice Projects

Background/Significance: Streptococcus pneumoniae is responsible for 20-60% of U.S. bacterial pneumonia cases and has a mortality rate of 10-30%. Invasive pneumococcal disease (IPD) occurs when streptococcus pneumoniae invades otherwise sterile sites. Adherence to immunization guidelines is 60-70% effective at preventing IPD. Co-administration of pneumococcal and influenza vaccines has shown promise at increasing uptake of the pneumococcal vaccine and enhancing immunological response. Population/Setting: A state-run Department of Corrections (DOC) clinic system serving just over 30,000 individuals was the site for this project. Incarcerated individuals present an increased risk of contracting pneumococcal disease due to close living quarters. Other risk factors such …


Psychiatric Mental Health Nurse Practitioner Perceptions Of How Providing Patient Care During The Covid-19 Pandemic Affected Their Own Mental Health, Linda Cabage May 2024

Psychiatric Mental Health Nurse Practitioner Perceptions Of How Providing Patient Care During The Covid-19 Pandemic Affected Their Own Mental Health, Linda Cabage

Electronic Theses and Dissertations

Public health concerns were prominent during the COVID-19 pandemic, particularly regarding rising cases of anxiety and depression among adults. U.S. healthcare providers were especially affected by the unrelenting demands on their time and service. Psychiatric Mental Health Nurse Practitioners (PMHNPs) provided patient care during the pandemic to meet the increasing need for mental health services as people began experiencing mood disturbances such as anxiety, depression, and grief. The purpose of this qualitative study was to explore the perceived effect of the COVID-19 pandemic on the mental health of PMHNPs. A qualitative design using the interpretive description method allows researchers to …


Bayesian Estimation Of Reproduction Numbers From Distributions Of Outbreaks Sizes: Branching Process Approach, Alberta Araba Johnson May 2024

Bayesian Estimation Of Reproduction Numbers From Distributions Of Outbreaks Sizes: Branching Process Approach, Alberta Araba Johnson

Theses and Dissertations

The Generalized Poisson distribution is useful in modeling epidemiological processes as a branching stochastic processes problem. Our goal is to construct accurate and reliable estimators for the reproduction number (R0) (i.e., the number of secondary infections), particularly in the context of disease outbreaks modeled by a Galton-Watson process. Towards this goal, we construct the classical Bayes estimator, the Maximum Likelihood estimator, and the Empirical Bayes (EB) estimator under the Square Error Loss function in Chapter II. We prove that the Empirical Bayes estimator is asymptotically optimal and estimate the rate of convergence. We then proceed to monotonize the Empirical Bayes …


Perinatal Buprenorphine Effects On Offspring Growth, Opioid Withdrawal, And Brain Morphology In Rats, Parker Barnes May 2024

Perinatal Buprenorphine Effects On Offspring Growth, Opioid Withdrawal, And Brain Morphology In Rats, Parker Barnes

Electronic Theses and Dissertations

Opioid use disorder (OUD) impacts 5.6 million people in the US. Buprenorphine (BUP) is a commonly prescribed opioid medication used to treat OUD, including in pregnant women. However, opioid use during pregnancy is associated with poorer infant outcomes including reduced fetal growth, neurodevelopmental deficits, and neonatal opioid withdrawal syndrome (NOWS). Recent clinical data suggests that providing mothers with a lower dose of BUP may result in fewer negative outcomes in infants. Here, a preclinical rodent model of low-dose perinatal BUP exposure was used to study offspring health outcomes in the neonate, juvenile, and adolescent offspring. Dams were given clinically relevant …


Inhibition Of Pro-Inflammatory Lipid Mediators By Yersinia Pestis., Amanda Brady May 2024

Inhibition Of Pro-Inflammatory Lipid Mediators By Yersinia Pestis., Amanda Brady

Electronic Theses and Dissertations

Yersinia pestis causes the human disease known as plague. A key manifestation of plague is a delayed inflammatory response. Because this delay in inflammation is required for virulence, I was interested in defining the molecular mechanisms used by Y. pestis to evade immune recognition. Eicosanoids are produced early during infection and necessary to initiate a rapid inflammatory response. Despite the importance of these lipids in mediating inflammation, the role of eicosanoids during plague has not been previously investigated. Using an intranasal mouse model infection, I determined the kinetics of eicosanoid synthesis during pneumonic plague. I further demonstrated that LTB4 …


A Sensor-Based Simulation Method For Spatiotemporal Event Detection, Yuqin Jiang, Andrey A. Popov, Zhenlong Li, Michael E. Hodgson, Binghu Huang May 2024

A Sensor-Based Simulation Method For Spatiotemporal Event Detection, Yuqin Jiang, Andrey A. Popov, Zhenlong Li, Michael E. Hodgson, Binghu Huang

Faculty Publications

Human movements in urban areas are essential to understand human–environment interactions. However, activities and associated movements are full of uncertainties due to the complexity of a city. In this paper, we propose a novel sensor-based approach for spatiotemporal event detection based on the Discrete Empirical Interpolation Method. Specifically, we first identify the key locations, defined as “sensors”, which have the strongest correlation with the whole dataset. We then simulate a regular uneventful scenario with the observation data points from those key locations. By comparing the simulated and observation scenarios, events are extracted both spatially and temporally. We apply this method …


Oxidative Phosphorylation In Melanoma Brain Metastases: A Regulator Of The Tumor Immune Landscape, Renato A. Guerrieri May 2024

Oxidative Phosphorylation In Melanoma Brain Metastases: A Regulator Of The Tumor Immune Landscape, Renato A. Guerrieri

Dissertations and Theses (Open Access)

Previously, we demonstrated via RNA-sequencing analysis of murine intracranial melanoma tumors that pharmacologic inhibition of oxidative phosphorylation (OXPHOS) results in increased expression of genes consistent with activated anti-tumor immune responses. The central hypothesis of this dissertation is that OXPHOS plays a critical role in the pathogenesis and immune regulation of melanoma brain metastases (MBMs).

The functional significance of OXPHOS was assessed through genetic inhibition, involving knockout (KO) of key regulatory genes such as Ppargc1a (PGC1a) and Ndfus4 (NDUFS4), a component of mitochondrial complex I. PGC1a KO in an RCAS-TVA mouse model of autochthonous lung and brain tumors developing from primary …


Targeting Coenzyme A Biosynthesis For Antifungal Development., Jessica Regan May 2024

Targeting Coenzyme A Biosynthesis For Antifungal Development., Jessica Regan

Theses and Dissertations (ETD)

An estimated 1.5 million people die each year from invasive fungal infections (IFIs) involving dissemination to the deeper organs via the bloodstream, with estimated healthcare costs of over $7 billion in the U.S. alone. Collectively, several Candida species account for more than 75% of disseminated fungal infections in the U.S., with attributable mortality rates ranging 35-75%. Unfortunately, the prospect of curing these infections is limited by the modest efficacy of the available antifungal drugs: the azoles, echinocandins, and amphotericin B. Approximately one-third of patients with disseminated Candida infections are non-responsive to treatment with the azoles, and favorable response rates are …


Fragile: Handle With Care A Conversation On Trauma, Flashbacks, And Seeing A Therapist When You Need One, Gloria Aragon May 2024

Fragile: Handle With Care A Conversation On Trauma, Flashbacks, And Seeing A Therapist When You Need One, Gloria Aragon

All Theses

The primary content of this creative thesis is a complete manuscript titled Fragile. This is a work of realistic fiction with a central theme of childhood trauma. Additionally, this thesis contains a critical essay entitled, “Moving On: A Discussion on Flashbacks and Childhood Trauma in Fiction”.


Effect Of Source Of Trace Minerals On Nutrient Digestibility And Rumen Fermentation Of Dairy Cows, Cesar Velasquez Rios May 2024

Effect Of Source Of Trace Minerals On Nutrient Digestibility And Rumen Fermentation Of Dairy Cows, Cesar Velasquez Rios

All Theses

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Exploring The Correlates And Predictors Of Covid-19 Vaccine Hesitancy And Uptake Among People Living With Hiv/Aids In Tennessee, Charles Olomofe May 2024

Exploring The Correlates And Predictors Of Covid-19 Vaccine Hesitancy And Uptake Among People Living With Hiv/Aids In Tennessee, Charles Olomofe

Electronic Theses and Dissertations

Background

The administration of the COVID-19 vaccines has met with resistance and hesitance from different population groups including people living with HIV/AIDS (PLWHA). It is concerning to know that PLWHAs are showing a higher rate of COVID-19 vaccine hesitancy than the general population. The objective of this study is to synthesize the literature and determine the correlates and predictors of COVID-19 vaccine hesitancy among PLWHA using primary and secondary data.

Methods

A scoping review was conducted to identify and summarize studies on COVID-19 vaccine hesitancy among PLWHA using the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) Extension for …


Changes In Young Adults’ Perspective On Ageism After Participating In A Virtual Nutrition Education Program With Older Adults, Julianne Hensley May 2024

Changes In Young Adults’ Perspective On Ageism After Participating In A Virtual Nutrition Education Program With Older Adults, Julianne Hensley

Electronic Theses and Dissertations

The growing older adult population has led to increased ageist tendencies among younger generations. Previous research suggests that ageism is associated with cognitive and physical decline among older adults. This mixed-methods research project examined changes in ageist perceptions among graduate student facilitators and undergraduate nutrition ambassadors after participating in a training that included information about healthy aging, addressing ageism, and communicating with older adults. Results from a secondary data analysis of pre-test/post-test data and thematic analysis of semi-structured interviews with facilitators of Socially Nutritious, a virtual nutrition education program for older adults, indicate that ageist perceptions decreased after the …


Investigation Of Hematologic Findings Related To Brucellosis In Anatolian Region, Mehmet Çelik, Yusuf Arslan, Ertuğrul Topcu, Mustafa Serhat Şahinoğlu, Deniz Altındağ, Esra Gürbüz, Ebru Atalay, Sümeyye Kışlak Demircan, Salih Emre, Yasemin Kırık, Pınar Yürük Atasoy, Deniz Özer, Davut İpek, Ebru Doğan, Seval Bilgiç Atlı, Evrim Gülderen Kuşçu, Sevil Alkan, Yeliz Çiçek, Esra Yüksekkaya, Özlem Aldemir, Ahmet Şahin, Fatma Yekta Ürkmez, Sevda Özdemir Al, Riyad Boran, Serpil Oğuz Mızrakçı, Mehmet Reşat Ceylan, Hamza Erdoğdu, Süda Tekin May 2024

Investigation Of Hematologic Findings Related To Brucellosis In Anatolian Region, Mehmet Çelik, Yusuf Arslan, Ertuğrul Topcu, Mustafa Serhat Şahinoğlu, Deniz Altındağ, Esra Gürbüz, Ebru Atalay, Sümeyye Kışlak Demircan, Salih Emre, Yasemin Kırık, Pınar Yürük Atasoy, Deniz Özer, Davut İpek, Ebru Doğan, Seval Bilgiç Atlı, Evrim Gülderen Kuşçu, Sevil Alkan, Yeliz Çiçek, Esra Yüksekkaya, Özlem Aldemir, Ahmet Şahin, Fatma Yekta Ürkmez, Sevda Özdemir Al, Riyad Boran, Serpil Oğuz Mızrakçı, Mehmet Reşat Ceylan, Hamza Erdoğdu, Süda Tekin

Saudi Medical Journal

Objectives: To investigate the prevalence of hematologic findings and the relationship between hemogram parameters and brucellosis stages in patients. Methods: This multi-center study included patients older than 16 years of age who were followed up with a diagnosis of brucellosis. Patients’ results, including white blood cell, hemoglobin, neutrophil, lymphocyte, monocyte, mean platelet volume, platelet and eosinophil counts were analyzed at the initial diagnosis. Results: In this study 51.3% of the patients diagnosed with brucellosis were male. The age median was 45 years for female and 41 years for male. A total of 55.1% of the patients had acute brucellosis, 28.2% …


Mast Cells In Mammary Carcinoma, Alexandria M. Ashbaugh May 2024

Mast Cells In Mammary Carcinoma, Alexandria M. Ashbaugh

Undergraduate Honors Theses

Breast cancer (BC) is an aggressive disease that takes the lives of thousands of women every year. Although knowledge and treatment of this disease have improved over the years, much is still to be discovered about BC. One area of expertise that we are currently trying to learn more information about is the mast cell (MC) and its role in BC growth and development. The MC is an immune system component discovered in tumors' extracellular matrix (ECM). As a tumor grows within body tissues, the tumor recruits the MC from surrounding connective tissues to the tumor, using signaling cytokines such …


Concepts In Animal Parasitology: Master Bibliography, Sue Ann Gardner May 2024

Concepts In Animal Parasitology: Master Bibliography, Sue Ann Gardner

Concepts in Animal Parasitology

Master bibliography for the open educational resource/open access textbook Concepts in Animal Parasitology, Scott L. Gardner and Sue Ann Gardner, editors, published by Zea Books, Lincoln, Nebraska, United States, 2024. This includes the references from literature cited and suggested supplemental reading.


Employing Digital Pcr For Enhanced Detection Of Perinatal Toxoplasma Gondii Infection: A Cross-Sectional Surveillance And Maternalinfant Outcomes Study In El Salvador, Mary K. Lynn, Marvin Stanley Rodriguez Aquino, Pamela Michelle Cornejo Rivas, Xiomara Miranda, David F. Torres-Romero, Hanson Cowan, Madeleine M. Meyer, Willber D. Castro-Godoy, Mufaro Kanyangarara Ph.D., Stella C.W. Self Ph.D., Ms, Berry A. Campbell, Melissa S. Nolan Ph.D., Mph May 2024

Employing Digital Pcr For Enhanced Detection Of Perinatal Toxoplasma Gondii Infection: A Cross-Sectional Surveillance And Maternalinfant Outcomes Study In El Salvador, Mary K. Lynn, Marvin Stanley Rodriguez Aquino, Pamela Michelle Cornejo Rivas, Xiomara Miranda, David F. Torres-Romero, Hanson Cowan, Madeleine M. Meyer, Willber D. Castro-Godoy, Mufaro Kanyangarara Ph.D., Stella C.W. Self Ph.D., Ms, Berry A. Campbell, Melissa S. Nolan Ph.D., Mph

Faculty Publications

Toxoplasma gondii is a parasitic infection that can be transmitted in utero, resulting in fetal chorioretinitis and other long-term neurological outcomes. If diagnosed early, pregnancysafe chemotherapeutics can prevent vertical transmission. Unfortunately, diagnosis of acute, primary infection among pregnant women remains neglected, particularly in low-andmiddle-income countries. Clinically actionable diagnosis is complex due to the commonality of infection during childhood and early adulthood which spawn long-last antibody titers and historically unreliable direct molecular diagnostics. The current study employed a cross-sectional T. gondii perinatal surveillance study using digital PCR, a next generation molecular diagnostic platform, and a maternal-fetal outcomes survey to ascertain the …


Novel Roles Of Microtubule-Associated Tau In Radiation-Induced Brain Injury, Riya Thomas, Riya Thomas May 2024

Novel Roles Of Microtubule-Associated Tau In Radiation-Induced Brain Injury, Riya Thomas, Riya Thomas

Dissertations and Theses (Open Access)

Injury responses in cells lacking proliferation capacity such as terminally differentiated neurons consists of complex mechanisms to ensure cellular homeostasis. Brain tumor patients undergoing radiation therapy experience cognitive impairments similar to those seen in patients suffering from neurodegenerative diseases. Despite the plethora of research into radiation effects on proliferating brain cells, the impact of radiation on differentiated, post-mitotic neurons, including their structural and functional alterations, remain largely elusive. However, microtubule-associated tau, an important partner of cytoskeletal structural stability emerges as a pivotal player in the radiation-induced neuronal injury response, demonstrating compartmentalized functions such as repair-centric mechanisms and synaptic homeostasis. This …


Psychiatric Morbidity Among Patients On Treatment For Tuberculosis At A Tertiary Referral Hospital In Western Kenya, Robina Momanyi, Edith Kwobah, Philip Owiti, Henry Nyamogoba, Lukoye Atwoli May 2024

Psychiatric Morbidity Among Patients On Treatment For Tuberculosis At A Tertiary Referral Hospital In Western Kenya, Robina Momanyi, Edith Kwobah, Philip Owiti, Henry Nyamogoba, Lukoye Atwoli

Internal Medicine, East Africa

Background Mental disorders account for nine percent of the overall global burden of disease and are among the top ten leading causes of disability. Mental illness and tuberculosis share risk factors including poverty, overcrowding, stigma, poor nutrition, substance use and retro-viral disease co-infection. Presence of mental illness in tuberculosis delays health-seeking, affects drug adherence, increases cost of treatment, prolongs disease duration, lowers quality of life, and increases mortality. Early diagnosis, linkage, and treatment of psychiatric morbidity among patients with tuberculosis would improve outcomes for both. This study thus aimed to determine the prevalence and factors associated with psychiatric morbidity among …


Covid-19 And Unemployment Dynamics: A Regional Analysis In The United States, Keesha Queenie St. John May 2024

Covid-19 And Unemployment Dynamics: A Regional Analysis In The United States, Keesha Queenie St. John

Theses

The influence of the COVID-19 pandemic on unemployment rates in several US locations is examined in this research article. We investigate the intricate relationships between COVID-19 cases, mortality, GDP per capita, and unemployment rates through a thorough study of the data. The study sheds insight into the complex interaction between health crises and labor markets by revealing considerable differences in how these factors affect unemployment in various geographic locations.Unexpectedly, key findings show that places with higher COVID-19 cases frequently have lower unemployment rates. This trend is related to several variables, including critical sectors and public health activities. The positive correlation …


The Role Of Oncomodulin In The Central Nervous System Inflammation, Evan Paltjon May 2024

The Role Of Oncomodulin In The Central Nervous System Inflammation, Evan Paltjon

Honors Theses

Acoustic overexposure in mice leads to an excess of calcium influx in outer hair cells (OHCs) and causes permanent hearing loss due to death of OHCs. Oncomodulin is a parvalbumin calcium buffering protein located in OHCs of the cochlea. Early pilot studies indicate that genetic deletion of OCM results in immune-related pathology throughout the cochlea. Why and how this occurs is unknown. Studies in wild type (WT) and OCM knockout (KO) mice demonstrate greater numbers of immune cells are associated with noise exposure in an OCM knockout than in WT. Expression of toll-like receptor 4 (TLR4) leads to the recruitment …


Prison Parts: The Theological-Ethical Problem Of Using Prisoners As Living Organ Donors, Eryn Reyes Leong May 2024

Prison Parts: The Theological-Ethical Problem Of Using Prisoners As Living Organ Donors, Eryn Reyes Leong

Say Something Theological: The Student Journal of Theological Studies

This paper is a theological and ethical reflection of Massachusetts House Bill 2333, which would reduce prison sentences on the condition that state prisoners donate bone marrow or an organ. Looking specifically at agency and bodily integrity as the two facets of imago Dei that are implicated by House Bill 2333, I address the crucial question: Does House Bill 2333 distort the dignity of prisoners as imago Dei by incentivizing living prisoners to donate their body parts in exchange for freedom? Using Margaret A. Farley’s justice framework articulated in Just Love: A Framework for Christian Sexual Ethics (2006), this paper: …


The Role Of Anti-Viral Immune Response On The Therapeutic Efficacy Of Oncolytic Virotherapy For High-Grade Gliomas, Dong Ho Shin Phd May 2024

The Role Of Anti-Viral Immune Response On The Therapeutic Efficacy Of Oncolytic Virotherapy For High-Grade Gliomas, Dong Ho Shin Phd

Dissertations and Theses (Open Access)

Currently, there is no effective treatment for high-grade gliomas that are resistant to conventional treatments and immune checkpoint blockade therapies. Oncolytic viruses offer a new treatment modality by selectively replicating in cancer cells and inducing anti-tumor immunity. Among these viruses, the oncolytic adenovirus Delta-24-RGD has shown safety and efficacy in clinical trials for high-grade gliomas. Strategies to improve the efficacy of oncolytic virotherapy have aimed to heighten the immunogenicity of oncolytic viruses, either by incorporating immune-stimulating transgenes or by combining treatments with immune checkpoint blockades. However, such strategies may inadvertently trigger heightened immune responses to viral antigens, which may not …


Investigating The Role Of The Gut Microbiota On Immune Checkpoint Inhibitor-Mediated Colitis, Taylor Halsey, Robert Jenq May 2024

Investigating The Role Of The Gut Microbiota On Immune Checkpoint Inhibitor-Mediated Colitis, Taylor Halsey, Robert Jenq

Dissertations and Theses (Open Access)

Immune checkpoint inhibitors (ICIs) have been revolutionary in the fight against cancer by recruiting the host immune system as an agent for attack on malignant cells. Unfortunately, immune-related adverse events (irAEs), including ICI-mediated colitis (IMC), are common side effects that result from immune cell mediated damage on healthy tissues. Recent studies have highlighted a role for the gut microbiota in modulating ICI-mediated anti-tumor responses, but less is known regarding how the gut microbiota may impact on irAEs. Considering that the gastrointestinal tract harbors thousands of unique microbial species, many of which are known to modulate the immune system, microbes and …


Loss Of Ptdss1 In Tumor Cells Improves Anti-Pd-1 Therapy, Jielin Liu May 2024

Loss Of Ptdss1 In Tumor Cells Improves Anti-Pd-1 Therapy, Jielin Liu

Dissertations and Theses (Open Access)

PTDSS1 (Phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of PTDSS1 in tumor cells increased expression of IFNγ-regulated genes, including B2m, Cxcl9, Cxcl10, and Stat1. Loss of PTDSS1 in tumor cells also led to increased expression of MHC-I, which was associated with increased expression of cytolytic function related genes in CD8+ T cells and increased frequency of an iNOS+ myeloid subset. A gene signature derived from the iNOS+ myeloid …


Exploring The Role Of Il-1Β/Il-1r In The Pathogenesis Of K-Ras Mutant Lung Cancer, Avantika Krishna May 2024

Exploring The Role Of Il-1Β/Il-1r In The Pathogenesis Of K-Ras Mutant Lung Cancer, Avantika Krishna

Dissertations and Theses (Open Access)

As the leading cause of cancer-related deaths worldwide, the development of targeted therapeutics to treat lung cancer remains crucial. Non-small cell lung cancer (NSCLC), the most common histological subtype predominantly comprises lung adenocarcinoma with driver mutations in the K-ras oncogene (KM-LUAD). KM-LUAD progression partly occurs through activation of the NF-κB pathway initiating an inflammatory response and creating a pro-tumor microenvironment. Notably, the pro-inflammatory cytokine IL-1β a potent activator and product of the NF-κB pathway is elevated in the lungs and sera of KM-LUAD patients. We have shown that IL-1β blockade promotes an anti-tumor immune phenotype in a mouse model of …


Rna Knockdown Of The Immune Checkpoint Vista Promotes Tumor Regression, Brittany Morrow, Brittany A. Morrow May 2024

Rna Knockdown Of The Immune Checkpoint Vista Promotes Tumor Regression, Brittany Morrow, Brittany A. Morrow

Dissertations and Theses (Open Access)

Blockade of negative immune regulators for example CTLA-4, and PD-1/PD-L1 has proven to be a clinically effective strategy to enhance tumor specific immune responses. Recently discovered novel immunoglobulin superfamily ligand V-domain Ig suppressor of T-cell Activation (VISTA) is a new target for immunotherapy. VISTA expression is specifically upregulated on tumor infiltrating myeloid cells such as dendritic cells (DCs), tumor associated macrophages (TAMs) and myeloid derived suppressor cells (MDSCs). In addition, VISTA expression is increased on tumor-infiltrating regulatory T cells (Tregs) compared to those in the periphery. VISTA has been shown to suppress effector T cells through multiple mechanisms, primarily by …