Immunology and Infectious Disease Commons^™

Engineering Fsh-Cer T Cells To Enhance Response To Epithelial Ovarian Cancer, Nolan J. Beatty

USF Tampa Graduate Theses and Dissertations

Ovarian cancer remains a significant cause of cancer-related mortality, with epithelial ovarian cancer (EOC) being the most common subtype. Despite advances in treatment, the 5-year survival rate for late-stage EOC remains low due to factors such as tumor heterogeneity and an immunosuppressive tumor microenvironment (TME). This study investigates the therapeutic potential of chimeric endocrine receptor (CER) T cells engineered to express follicle stimulating hormone (FSH) in a syngeneic mouse model of EOC expressing follicle stimulating hormone receptor (ID8-FSHR). We compared two different co-stimulatory domains—CD28ζ and 4-1BBζ—in FSH-CER T cells and found that FSH-CD28ζ CER T cells exhibited enhanced cytotoxicity, proliferation, …

Association Of Social Isolation, Loneliness, Social Strain And Support With Cancer Onset, And Frailty And All-Cause Mortality In People With Cancer, Joanne Elayoubi

USF Tampa Graduate Theses and Dissertations

Cancer is the second leading cause of death both in the United States and globally and for individuals over sixty-five. In 2026, approximately 2,114,850 new cancer cases are projected to emerge according to the National Center for Health Statistics (Siegel et al., 2026). Cancer incidence is increasing, making older adults sixty-five and older at risk of frailty and mortality following cancer. Although social isolation, loneliness, lack of social support, and social strain have been found to be risk factors for poor health and mortality, it is not clear the extent to which social relationships are associated with incident cancer, and …

Targeting Cancer With T Cells: Preclinical And In Silico Insights To Improve Immunotherapies, Nina Obertopp

USF Tampa Graduate Theses and Dissertations

T-cell–based immunotherapies are often constrained by limited trafficking and persistence in tumors and by functional exhaustion under chronic antigen exposure. This dissertation addresses these barriers through two distinct strategies: (i) preclinical studies testing how radiation therapy modulates tumor-infiltrating lymphocytes (TIL) therapy, and (ii) agent based modeling (ABM) to optimize treatment day treatment-free intervals (TFI) in T-cell engager (TCE) therapy. (i) In a human papillomavirus–positive (HPV⁺) head-and-neck cancer (HNC) model, a single local-dose of RT (8 Gy) delivered five days before tumor harvest increased the success and functional quality of ex vivo TIL outgrowth from tumor fragments, enriching polyfunctional CD8⁺ subsets. …

Ifnγ-Driven Skewing Towards Th1 Over Th17 Differentiation Underlies Crs And Neutropenia In Car-T Therapy, Payal Goala

USF Tampa Graduate Theses and Dissertations

CAR-T therapy has improved overall and complete response rates, andprolonged progression free survival of patients with relapsed/refractory hematological malignancies. The short-term and long-term impacts of anti-CD19 CAR-T products on the immune landscape of B cell malignancies has garnered considerable attention in recent years. Most notably, a subset of patients experience high-grade cytokine toxicities, including cytokine release syndrome and immune cell-associated hematologic toxicity that manifest as prolonged cytopenia. Whereas etiology of CRS is more well established, the mechanisms leading to CAR-T associated cytopenia remains elusive. Rejeski et. al. showed that severe cytopenia in patients post CAR-T treatment led to frequent infections …

Exploring The Behaviors Of Women Who Are Mentally Thriving With Autoimmune Disease: A Mixed Methods Approach, Emilie Ann Ellenberg

USF Tampa Graduate Theses and Dissertations

Autoimmune diseases encompass a variety of conditions that impact millions of Americans, with a higher prevalence among women than men. These diseases involve immune system dysregulation, leading to tissue damage and dysfunction. Despite progress in understanding their underlying mechanisms, important aspects remain inadequately understood, such as the relationships among immune dysregulation, medical outcomes, and psychiatric comorbidities. Preliminary qualitative research indicates that perceived diagnostic invalidation leads to the mental health needs among women with autoimmune diseases often being unmet, and behavioral health help-seeking behaviors being reduced. Although perceived diagnostic invalidation can lead to increased mental health symptomology and decreased help-seeking behaviors, …

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 …

Targeting Tumor Microenvironmental Factors In Bladder Cancer To Enhance Responses With Immunotherapy, Sarah Bazargan

USF Tampa Graduate Theses and Dissertations

Bladder cancer is the tenth most common cancer in the world and has one of the highest recurrence rates. Despite the local delivery options and mutational status of bladder tumors, responses with immunotherapies have been limited with low durability. The bladder tumor microenvironment is enriched with highly immunosuppressive populations and harsh conditions that restrict anti-tumor immunity and subsequently attenuate immunotherapy response. We predict that targeting two of these immunosuppressive components, namely acidity and myeloid derived suppressor cells (MDSCs), will bolster T cell responses and enhance outcomes with immunotherapy. In Chapter 2, we characterized the effects of acidity on T cell …

The Role Of L-Fucose In Dendritic Cell Antigen Presentation And Polarization, Chase J. Burton

USF Tampa Graduate Theses and Dissertations

Since the FDA approval of IL-2 in cancer treatment in the 1980s, immunotherapy has emerged as the standard of care for several tumor types (e.g., melanoma, lung, bladder, colorectal). However, approximately 70 percent of cancer patients, independent of prior treatment or staging, administered immunotherapy will not achieve complete responses and will exhibit disease progression. Several factors have been identified to contribute to treatment failure, including the accumulation of intratumoral immunosuppressive cell populations, insufficient tumor-infiltrating anti-tumor immune populations, or the occurrence of immunoediting on tumor cells. Current strategies to circumvent immunosuppression either lack durable response to new immunosuppressive mechanisms the tumor …

Characterization And Reprogramming Of T-Cell Metabolic Dysfunction In Chronic Lymphocytic Leukemia For Improved Adoptive Cell Therapy, Wael B. Gamal

USF Tampa Graduate Theses and Dissertations

Chronic lymphocytic leukemia (CLL) is a predominant B-cell malignancy impacting elderly populations in Western societies. Targeted therapies have revolutionized the CLL treatment landscape. Still, patients often require long-term therapy and are subject to drug-induced resistance and severe toxicities, for which CLL is still considered an incurable disease. T-cell-based immunotherapy, particularly chimeric antigen receptor (CAR) T cells, has shown remarkable success, leading to various FDA approvals in hematological malignancies. Nonetheless, CAR T-cell therapy success rate is limited in CLL because of the dysfunctional nature of T cells. CLL T cells exhibit skewing toward immunosuppressive and terminally differentiated phenotypes, leading to hindrances …

Macrophage-Driven Car T Cell Resistance In B Cell Lymphoma, Sae Bom Lee

USF Tampa Graduate Theses and Dissertations

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of patients with relapsed/ refractory large B cell lymphoma (LBCL). Despite its promising efficacy, a subset of patients experiences primary resistance or relapse. In Chapter 2, we explore the tumor microenvironment (TME)-induced resistance mechanisms in patients with LBCL. Analysis of the intratumoral immune infiltrates in pre-infusion tumor biopsies revealed that the levels of immunoregulatory macrophages were elevated in patients who responded poorly to axicabtagene ciloleucel (axi-cel). Using preclinical mouse B cell tumor models, we found that the CAR T-cell-produced interferon-gamma (IFN-γ) enhanced the expression of inducible nitric oxide synthase (iNOS, …

Preliminary Investigation Of Differences In Host Mitochondria Membrane Potential During Toxoplasma Gondii Infection, Bryan L. Ortega

USF Tampa Graduate Theses and Dissertations

Toxoplasma gondii is an obligate intracellular protozoan with a broad host range of hosts, including various warm-blooded mammals, including humans. While infections can often be asymptomatic in immunocompetent individuals, they can pose significant risks to those who are immunocompromised, as well as pregnant women. Toxoplasmosis represents a significant burden on public health in the United States, with over 800,000 annual infections reported, often leading to severe complications such as symptomatic eye disease and congenital infections. Recent attention has developed regarding its potential association with human neuropathies such as Alzheimer's disease, dementia, and mood disorders. This project investigated differences in host …

Role Of The Glutamine-Polyamine-Hypusine Axis In Cd8+ T Cell Fate And Function, Aya Gamal Aly Sadek Elmarsafawi

USF Tampa Graduate Theses and Dissertations

T cells are critical effectors of the immune response against pathogens and malignancies and, given the recent success of T-cell immunotherapies in cancer, there is now an urgent need to enhance the efficacy and durability of T-cell immune responses to improve anti-tumor immunity. Formation of memory T cells is a critical step of a successful immune response as it ensures maintenance of long-term immunity and protection from re-exposure to foreign antigens. Notably, metabolism regulates the fate and function of T cells and is a powerful tool to modulate T-cell activity and memory differentiation. Accordingly, metabolic interventions to augment T-cell memory …

Role Of Short Interspersed Nuclear Elements (Sines) Of Maternally Imprinted Microrna Clusters In Hemochorial Placental Antiviral Immunity, Ishani Wickramage

USF Tampa Graduate Theses and Dissertations

The evolution of hemochorial placentas in which the fetal trophoblast is bathed in maternal blood has vastly improved fetal development and survival in primates and rodents, due to the enhanced efficiency of nutrient, gas and waste exchange between the mother and the fetus. However, the extensive contact between the fetal tissues and maternal blood in these placentas also poses an increased risk of vertical transmission of pathogens such as viruses from the mother to the fetus. In response to this selection pressure, hemochorial placentas have evolved robust defense mechanisms to protect the immunologically naive fetus. Unlike somatic cells that require …

Withaferin A And Immune Checkpoint Blocker Therapy For The Treatment Of Non-Small Cell Lung Cancer, Roukiah Khalil

USF Tampa Graduate Theses and Dissertations

Lung cancer is the first cause of cancer-related deaths in both men and women with an overall five-year survival rate of 28%. Although immune checkpoint blockers (ICBs) are currently FDA-approved for the treatment of non-small cell lung cancer (NSCLC), only 17-20% of patients achieve durable responses by the induction of immunologic memory. The lack of response in most patients can be attributed to the tumor-intrinsic or tumor-extrinsic immune resistance mechanisms. A biomarker of importance is the Programmed Death Ligand-1 (PD-L1), as higher PD-L1 expression is usually associated with a better response to ICBs. Although studies have attempted to combine ICBs …

Acetate-Encapsulated Linolenic Acid Liposomes Reduce Sars-Cov-2 And Rsv Infection, Andrew R. Mcgill

USF Tampa Graduate Theses and Dissertations

Coronavirus disease-19 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), is an ongoing pandemic-endemic. In the United States, it remains the third leading cause of death in 2022. SARS-CoV-2, an RNA virus, has a genome prone to rapid mutation, generating variant species capable of resisting therapies and vaccination efforts. However, it has been estimated that more than 40% of SARS-CoV-2 infections may be asymptomatic, which calls into question any biological differences between the asymptomatic and afflicted groups. Additionally, Respiratory Syncytial Virus (RSV) is the most significant cause of bronchiolitis and asthma in neonates, with an increasing burden on the …

Evaluation Of The Humoral Immune Responses To Plasmodium Vivax Circumsporozoite Protein (Csp)-Based Pre-Erythrocytic Vaccine Candidates, Jack Esquenazi

USF Tampa Graduate Theses and Dissertations

Malaria, caused by the apicomplexan Plasmodium spp. , is a major public health issue that impacts over one-third of the world’s population ,with Plasmodium vivax accounting for over 130 million clinical cases annually. The circumsporozoite protein (CSP) is the most abundant molecule on the surface of Plasmodium sporozoites and is considered a leading pre-erythrocytic stage vaccine candidate. CSP is essential for sporozoite maturation, migration, and invasion. Anti-CSP antibodies interrupt sporozoite migration and infection of hepatocytes thus reducing liver-stage burden. P. vivax CSP is composed of three subdomains: a highly polymorphic immunodominant central repeat region (CRR), conserved N-terminal ,and C-terminal subdomains. …

Preliminary Characterization And Functional Validation Of Pre-Erythrocytic Vaccine Candidates For The Malaria Parasite Plasmodium Vivax, Justin Lee Nicholas Iii

USF Tampa Graduate Theses and Dissertations

RTS,S/AS01, vaccine targeting malaria caused by Plasmodium falciparum, used in moderate to high malaria transmission, provides hope for pre-erythrocytic (PE) subunit malaria vaccine development. Despite this vaccine advance, efforts to develop an efficacious vaccine against the neglected parasite Plasmodium vivax have lagged. In addition, there exists a gap in our understanding of PE antigens that can induce broadly-neutralizing antibodies. In this dissertation, we provide the preliminary characterization of vaccine candidates targeting the PE of P. vivax. Through transcriptomic profiling data and a target product profile, we identified critical P. vivax antigens (SSP3, SPECT-1, and M2-MAEBL) that can potentially be targets …

Partial Characterization Of Plasmodium Falciparum Genes Implicated In Altered Artemisinin Stress Response, Caroline F. Simmons

USF Tampa Graduate Theses and Dissertations

Malaria is a parasitic illness caused by the Plasmodium spp., with an estimated 247 million malaria cases reported in 2021 across 84 endemic countries. Treatment of the deadliest malaria parasite, P. falciparum, relies on artemisinin combination therapies (ACTs). However, while ACTs have greatly decreased malaria mortality, this progress is threatened due to artemisinin (ART) partial resistance and ACT failure in Southeast Asia and Sub-Saharan Africa. SNPs to the Kelch13 (K13) gene are a well-characterized marker for ART resistance. However, increasing evidence that resistance to ART mediated by genes not related to K13 SNPs prompts the need to characterize other novel …

Histone Deacetylase 8 Is A Novel Therapeutic Target For Mantle Cell Lymphoma And Preserves Natural Killer Cell Cytotoxic Function, January M. Watters

USF Tampa Graduate Theses and Dissertations

This study demonstrates for the first time that HDAC8 function is critical for MCL survival, and abrogating its activity in human primary NK cells does not interfere with NK IgG antibody directed ADCC therapies ex vivo. Human NK cells, isolated from healthy donors, are highly resistant to HDAC8 inhibitor treatment with PCI-34051. Even at the highest concentration, 20uM, no toxicity was observed. Conversely, MCL cell lines representative of the aggressive MCL subtype, classical MCL, were especially sensitive to PCI-34051, an HDAC8 selective inhibitor, treatment. Blocking HDAC8 activity and/or abrogating expression through shRNA silencing induced significant DNA damage, hyperacetylation of SMC3, …

Utilizing Neoantigen-Specific Cd4* T Cells And Immune Checkpoint Modulation To Advance Adoptive Cell Therapy With Tumor-Infiltrating Lymphocytes For Metastatic Melanoma Patients, Maclean Scott Hall

USF Tampa Graduate Theses and Dissertations

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is a promising immunotherapeutic approach for patients with advanced solid tumors. Metastatic melanoma is a tumor type amenable to immunotherapy in part due to the presence of antigen-specific TIL. These T cells can be activated and expanded for ACT, which has resulted in relatively high rates of clinical responses. While numerous advances have been made, the inclusion of neoantigen-specific CD4+ T cells within TIL infusion products remains underexplored and therefore offers a significant opportunity for progress. Similarly, immune checkpoint inhibitors, specifically PD-1 blocking antibodies, augment antitumor immunity and may improve the outcomes …

Seroprevalence Of Sars-Cov-2 Antibodies, The Gut Microbiome, And Peripherally Circulating Cytokines In Pregnant Hispanic Females, Tina Susanna Mutka

USF Tampa Graduate Theses and Dissertations

Pregnant Hispanic females have been disproportionately impacted by SARS-CoV-2 andhave experienced high rates of asymptomatic or mildly symptomatic, unrecognized infection. Acute SARS-CoV-2 infection has been associated with gut microbiome changes and altered peripherally circulating cytokine levels in symptomatic, non-pregnant individuals.

This study investigated the seroprevalence of anti-SARS-CoV-2 IgG antibodies in a sample of pregnant Hispanic females (n = 197). A sub-sample of SARS-CoV-2 seropositive and seronegative pregnant Hispanic females were followed across pregnancy and their bacterial gut microbiome was characterized, and cytokine levels measured to investigate relationships between SARS-CoV-2 serostatus, the gut microbiome, and peripherally circulating cytokine levels across pregnancy. …

Determining The Role Of Dendritic Cells During Response To Treatment With Paclitaxel/Anti-Tim-3, Alycia Gardner

USF Tampa Graduate Theses and Dissertations

Intratumoral CD103+ dendritic cells (cDC1) are required for anti-tumor immune responses. In tumors that are poorly responsive to immunotherapeutic approaches targeting T cells, targeting cDC1 represents an alternative approach that may be useful in improving patient response rates. As such, it is critical to understand cDC1 function within tumors, and what may be preventing optimal function of cDC1. TIM-3 is a receptor that is highly expressed by cDC1 in murine and human mammary tumors, and TIM-3 blocking antibodies are currently being evaluated in clinical trials for a number of solid and hematological malignancies. In order to best design combinatorial therapeutic …

Development And Validation Of An Isothermal Amplification Assay For Eastern Equine Encephalitis Virus, Mikayla D. Maddison

USF Tampa Graduate Theses and Dissertations

Eastern Equine Encephalitis virus (EEEV) is a neurotrophic alphavirus for which there is no effective treatment or vaccine for humans. Periodic outbreaks in the Eastern United States represent an ongoing public health problem; Florida serves as the reservoir for EEEV for the rest of the country. Reverse transcription-polymerase chain reaction (RT-PCR) is the current gold standard for molecular diagnostic testing of the presence of EEEV in vectors. However, RT-PCR is technically complex and can be difficult for mosquito control districts to utilize. In order to provide a simple, cost-effective alternative for mosquito surveillance and control, a novel one step reverse …

Mechanisms And Mitigation: Effects Of Light Pollution On West Nile Virus Dynamics, Meredith E. Kernbach

USF Tampa Graduate Theses and Dissertations

Light pollution, or the presence of unnatural light at night, is a pervasive and growing problem across the globe. While often pictured in urban centers, light pollution is far reaching and can affect seemingly safe and minimally developed environments. For example, agricultural communities with artificial lighting near facilities can generate such light pollution in rural areas. Further, streetlights and illuminated billboards along roads and highways can generate light pollution far from cities. Given how pervasive this anthropogenic stressor is, it is surprising that not much is known about how artificial light at night, or ALAN, affects humans or wildlife, especially …

Defining Codes Based On The Consolidated Framework For Implementation Research In The Context Of The Implementing Universal Lynch Syndrome Screening, Jasmine A. Burton-Akright

USF Tampa Graduate Theses and Dissertations

Lynch syndrome (LS) is the most common hereditary cause of both colorectal cancer (CRC) and endometrial cancer (EC). Universal tumor screening (UTS) of newly diagnosed EC and CRC patients has been shown to be both an effective and economical approach to identify patients with LS and subsequently reduce future cancer s for patients and their family members. Despite its efficacy, LS UTS has not been consistently adopted across hospital systems and existing programs vary widely in their structure and execution. The Implementing Universal Lynch Syndrome Screening (IMPULSS) study aims to determine the critical factors necessary for successful implementation of LS …

Computing For Numeracy: How Safe Is Your Covid-19 Social Bubble?, Charles Connor

Numeracy

The COVID-19 pandemic has led many people to form social bubbles. These social bubbles are small groups of people who interact with one another but restrict interactions with the outside world. The assumption in forming social bubbles is that risk of infection and severe outcomes, like hospitalization, are reduced. How effective are social bubbles? A Bayesian event tree is developed to calculate the probabilities of specific outcomes, like hospitalization, using example rates of infection in the greater community and example prior functions describing the effectiveness of isolation by members of the social bubble. The probabilities are solved for two contrasting …

The Impact Of Myeloid-Mediated Co-Stimulation And Immunosuppression On The Anti-Tumor Efficacy Of Adoptive T Cell Therapy, Pasquale Patrick Innamarato

USF Tampa Graduate Theses and Dissertations

Adoptive T cell therapy (ACT) in combination with lymphodepleting chemotherapy is an effective strategy to induce the eradication of tumors, providing long-term regression in cancer patients. However, only a minority of patients that receive ACT with tumor infiltrating lymphocytes (TILs) exhibit durable benefit. Thus, there is an urgent need to define strategies that potentiate anti-tumor activity conducted by adoptively transferred T cells. In these studies, we aimed to identify novel strategies to enhance the therapeutic efficacy of ACT. Accordingly, we describe the disparate roles of myeloid cells in the context of ACT characterized by the augmentation of TIL proliferation in …

From R0 To The Herd: A Review Of The Rules Of Contagion, By Adam Kucharski, Nathan D. Grawe

Numeracy

Adam Kucharski. 2020. The Rules of Contagion: Why Things Spread--and Why They Stop; (London: Profile Books, Ltd.). Hardback ISBN 978-17-88-16019-3. E-book ISBN 978-17-82-83430-4.

Kucharski's well-timed Rules of Contagion provides an introduction to the mathematical and epidemiological principles behind contagious phenomenon. While the author's primary expertise stems from work on biological epidemics, the book points to examples from a wide range of fields including finance, psychology, computer science, and criminology. As such, selections of the book could be used by faculty in a wide range of classes to show how our recent experience with a viral epidemic might add to …

Non-Invasive Sex Determination And Genotyping Of Transgenic Brugia Malayi Larvae, Santiago E. Hernandez Bojorge

USF Tampa Graduate Theses and Dissertations

Lymphatic filariasis is a very painful and disfiguring helminth disease caused by the tissue nematodes Wuchereria bancrofti, Brugia malayi, and Brugia timori. This parasitosis is considered a Neglected Tropical Disease and it is a major public health burden for 72 tropical countries of Africa, Southeast Asia, the Caribbean, and South America. Despite the effectiveness of many control programs, there remains the need to develop new pharmacological agents to treat lymphatic filariasis, as most programs rely on a limited variety of drugs that are expensive, logistically difficult to obtain, and can lead to drug resistance. The Clustered Regularly Interspaced Short Palindromic …