Medicine and Health Sciences Commons^™

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 …

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, …

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 …

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 …

Identification Of Novel Hits Against, Ala A. Azhari

USF Tampa Graduate Theses and Dissertations

Leishmaniasis is a disease caused by obligate intracellular parasites of the genus Leishmania, including 20 species that are pathogenic to humans. Female sand fly is the known vector that can transmit the disease. Visceral leishmaniasis is the severe form of the disease that affects internal organs and can be fatal with inappropriate diagnosis or treatment. Leishmania donovani is the causative agent of visceral leishmaniasis. Approximately 350 million in 89 countries are at risk of infection. Around 2 million new cases are reported annually with 500,000 of these are visceral leishmaniasis. Current drug therapies are inadequate due to their toxicity, high …

Angiostrongylus Cantonensis: Epidemiologic Review, Location-Specific Habitat Modelling, And Surveillance In Hillsborough County, Florida, U.S.A., Brad Christian Perich

USF Tampa Graduate Theses and Dissertations

Angiostrongylus cantonensis is a parasitic nematode endemic to tropical and subtropical regions and is the leading cause of human eosinophilic meningitis. The parasite is commonly known as rat lungworm because the primary host in its lifecycle is the rat. A clinical overview of rat lungworm infection is presented, followed by a literature review of rat lungworm epidemiology, risk factors, and surveillance projects. Data collected from previous snail surveys in Florida was considered alongside elevation, population per square kilometer, median household income by zip code territory, and normalized difference vegetation index specific to the geographic coordinates from which the snail samples …

Cost-Effectiveness Analysis Of Targeted Herpes Zoster Vaccination In Adults 50-59 At Increased Cardiovascular Risk, Kathleen M. Glassner

USF Tampa Graduate Theses and Dissertations

Background: Over the last twenty years the incidence of herpes zoster (HZ) infection, also known as shingles, has been increasing among adults for unknown reasons. The economic burden of HZ is currently estimated at over $1 billion per year in the United States (U.S.) and is expected to increase as the susceptible adult population ages. HZ is caused by a re-activation of the varicella zoster virus (VZV), chicken pox, and more than 95% of adults living today carry the virus with a lifetime risk of 1 in 3 for developing HZ. In 2006 the FDA approved a vaccine for the …

Evaluation Of A Microsphere-Based Immunoassay (Mia) In Measuring Diagnostic And Prognostic Markers Of Dengue Virus Infection, Jason H. Ambrose

USF Tampa Graduate Theses and Dissertations

Infections with dengue viruses (DENV) constitute both a global problem as well as locally in Florida. DENV comprise four distinct serotypes of single-stranded RNA viruses and belong to the family Flaviviridae. DENV are among the most medically important arboviruses in the world and cases may currently exceed 400 million per annum. Additionally, dengue established its first recorded endemic transmission cycle in the state of Florida in over a half century, first within the Florida Keys during 2009-10 followed by an unrelated outbreak in Martin County in 2013. The clinical profile of DENV infections ranges from a mild febrile illness …

Synthesis, In Vitro Characterization And Applications Of Novel 8-Aminoquinoline Fluorescent Probes, Adonis Mcqueen

USF Tampa Graduate Theses and Dissertations

Malaria is a parasitic disease that is caused by the plasmodium parasite. Plasmodium infection has affected man for thousands of years. With advances in drug discovery over the past century, malaria has evolved to possess resistance to most mainline therapeutics. This war of drug discovery vs plasmodium evolution continues to be fought to this very day, with attempts to eradicate malaria worldwide. Frontline treatments such as chloroquine, artemisinin, and atovaquone/proguanil have all seen parasitic resistance in strains of P. vivax as well as P. falciparum. While plasmodium possesses resistance to most classes of anti-malarials, the 8-aminoquinoline (8-AQ) class has …

The Effect Of Antigen Polymorphisms On Serological Antibody Detection Assays Based Upon The, Kristi M. Miley

USF Tampa Graduate Theses and Dissertations

Onchocerca volvulus is a filarial parasite transmitted to humans by female Simulium spp. black flies. Infection with this parasite can cause blindness and severe skin disease among humans in Africa and the Americas. Enzyme-linked Immunosorbent Assay serological testing of OV-16 antigen is a diagnostic tool for determining effective elimination of the parasite. Programs typically rely on OV–16 ELISA to evaluate the progress towards interruption and/or elimination of disease by mass drug distribution of ivermectin and vector larvicidal control efforts. As elimination grows closer, monoclonal antibody positive controls for OV-16 ELISA become important to develop for Onchocerca testing due to the …

Development Of Tools For Stable Transfection In The Human Filarial Parasite Brugia Malayi Via The Piggybac Transposon System, Johan Chabanon

USF Tampa Graduate Theses and Dissertations

Brugia malayi is one of three species of nematode known to cause lymphatic filariasis (LF) in humans. LF infects over 120 million people, causing debilitating disease. Various global programs have been launched in the past 20 years to eliminate LF. These programs have greatly scaled up the resources and efforts allocated to halting the transmission and reducing disease burden. Only a few drugs are used to treat LF, and resistance is thus a devastating possibility. Research aimed at identifying new drug targets could therefore prove essential in elimination of LF.

Genetic manipulation of B. malayi has been limited to transient …

Antimalarial Exoerythrocytic Stage Drug Discovery And Resistance Studies, Lynn Dong Blake

USF Tampa Graduate Theses and Dissertations

Malaria is a devastating global health issue that affects approximately 200 million people yearly and over half a million deaths are caused by this parasitic protozoan disease. Most commercially available drugs only target the blood stage form of the parasite, but the only way to ensure proper elimination is to treat the exoerythrocytic stages of the parasite development cycle. There is a demand for the discovery of new liver stage antimalarial compounds as there are only two current FDA approved drugs for the treatment of liver stage parasites, one of which fails to eliminate dormant forms and the other inducing …

Targeting Histone Deacetylases In Melanoma And T-Cells To Improve Cancer Immunotherapy, Andressa Sodre De Castro Laino

USF Tampa Graduate Theses and Dissertations

Histone deacetylases (HDACs) are key mediators of gene expression and, thus, major regulators of cell function. As such, HDACs play a role in orchestrating tumor biology, and the use of small inhibitors targeting theses proteins is attractive for the field of cancer therapy. Indeed, several HDAC inhibitors have received FDA-approval for the treatment of malignancies, while a myriad of these compounds continue to be evaluated in clinical trials. Besides their direct impact on tumor growth, HDAC inhibitors have been shown to increase immunogenicity of cancer cells, facilitating generation of a productive immune response against tumors. Immunotherapeutic approaches take advantage of …

Antigen Specific Induced T Regulatory Cellular Therapy For Graft-Versus-Host Disease Following Allogeneic Bone Marrow Transplantation, Jessica Lauren Heinrichs

USF Tampa Graduate Theses and Dissertations

Allogeneic hematopoietic stem cell transplantation (allo-HCT) has been a successful cellular therapy for patients suffering from hematological malignancies for many decades; however, the beneficial effects of graft-versus-leukemia (GVL) are classically offset by graft-versus-host disease (GVHD). GVHD occurs when major and/or minor human leukocyte antigen (HLA) mismatches between donor and recipient cause rapid expansion and activation of donor effector T cells (Teffs) resulting in end organ damage to the recipient’s epithelial tissues. Given the lymphoproliferative nature of this disease, the standard treatment option is broad immunosuppression, which can result in primary disease relapse, steroid refractory GVHD, and/or opportunistic infection. A more …

Altered Intraerythrocytic Development Phenotypes Of Artemisinin-Resistant Plasmodium Falciparum Confer A Fitness Advantage, Amanda Hott

USF Tampa Graduate Theses and Dissertations

Resistance to artemisinin combination therapies (ACTs) has emerged in southeast Asia threatening the most widely used treatment against antimalarial-resistant Plasmodium falciparum worldwide. Artemisinin resistance has been associated with a reduced rate of parasite clearance following treatment with an ACT and is attributed to increased survival of ring-stage parasites. Single nucleotide polymorphisms (SNPs) in kelch gene (K13) has been associated with delayed in vivo clearance half-life of artemisinin-resistant P. falciparum and is the only known molecular marker of resistance. The absence of reliable in vitro phenotypes for artemisinin resistance has limited our understanding of the resistance mechanism(s) and fitness costs, therefore …

Mmv Malaria Box Activity Screening In Dormant Plasmodium Falciparum Phenotypes, Sandra Galusic

USF Tampa Graduate Theses and Dissertations

The causative agent of malignant tertian malaria, Plasmodium falciparum undergoes an arrested growth phenotype of its erythrocytic stage when under drug-stress. Recent artemisinin treatment failures seem to be indicative of such induction followed by recrudescence rather than actual therapeutic failure. Likewise, P. vivax hypnozoites are the prototypic dormants and the latent infections for which they are responsible prove most difficult to treat. Dihydroartemisinin, an artemisinin-derivative, can be used to exploit this mechanism by inducing a dormant state in ring-stage P. falciparum parasites and in turn, their recovery may be used as a screening period for compounds that inhibit or foster …

Implications Of Human Umbilical Cord Blood Cells: An Immunotherapeutic Strategy For Alzheimer's Disease, Donna Darlington

USF Tampa Graduate Theses and Dissertations

ABSTRACT

Alzheimer's disease (AD) is the most common progressive age related dementia and the fourth major cause of mortality in the elderly in the United States. AD is pathologically characterized by deposition of amyloid beta (Aβ) plaques in the brain parenchyma and neurofibrillary tangles (NFTs) within the neuronal soma. While pharmacological targets have been discovered, current strategies for the symptomatic or disease-modifying treatment of AD do not significantly slow or halt the underlying pathological progression of the disease. Consequently, more effective treatment is needed. One possibility for amelioration is using human umbilical cord blood cell (HUCBC) therapy. HUCBCs comprise a …

Pathogenic Mechanisms And Signaling Pathways In Plasmodium Falciparum, Jennifer L. Sedillo

USF Tampa Graduate Theses and Dissertations

Plasmodium falciparum is a human intracellular parasite that is the causative agent of a deadly form of malaria. This species alone is responsible for 200 million cases of malaria annually resulting in over 1 million deaths worldwide. The excessive mortality due to P. falciparum infection is due to its ability to cause severe pathogenesis through hyperparasitemia and cytoadherence defined as the ability of infected red blood cells to adhere to host vasculature. Cytoadherence is mediated through the export of parasite proteins to the surface of the infected red blood cell (RBC). Exported proteins have been identified but the pathway for …

Molecular Evidence For Vector Implication Of Onchocerca Lupi In Los Angeles County, Ca, Shanna June Bolcen

USF Tampa Graduate Theses and Dissertations

Onchocerca is a genus of roundworm most commonly associated with the human infection onchocerciasis, or river blindness. While typically a zoonotic infection of ungulate populations, canine cases (Onchocerca lupi) have been identified in the United States and Greece. In 2012, Los Angeles County, Veterinary Public Health Program identified 3 cases of Onchocerca spp. infections in domestic canines. Samples from the ensuing blackfly collections were sent to the Global Health Infectious Disease Research Unnasch Laboratory for parasite isolation and vector species identification. Species-specific primers were designed and optimized for O. lupi using a non- specific cytochrome oxidase (COI) gene target (689bp) …

Relationship Between Dysphoric Moods, Risk-Taking Behaviors, And Toxoplasma Gondii Antibody Titers In Female Veterans, Allyson Radford Duffy

USF Tampa Graduate Theses and Dissertations

The number of female veterans is increasing daily. Previous research conducted on veterans has focused primarily on males or with small samples of females. Depression and suicidality are becoming increasingly evident in returning veterans. Toxoplasma gondii is an intracellular parasite that is common in the Middle East and has been reported to cause changes in personality and behavior.

The purpose of the current study was to examine relationships between T. gondii antibody titer and socioeconomic variables, dysphoric moods, and risk-taking behaviors in a sample of 70 female veterans. Blood samples were collected and analyzed for T. gondii antibody titer and …

Prenatal Stress, Depression, And Herpes Viral Titers, Pao-Chu Hsu

USF Tampa Graduate Theses and Dissertations

Recent studies suggest that some cases of prenatal depression may be associated with reactivation of latent infections of the herpesvirus family. The possible relationships among stress, prenatal depression, and herpes viral reactivation in pregnancy are understudied and the molecular pathways such as the neuroimmune biogenic amine pathway are unidentified. Chronic stress shifts the T helper-1 cell (Th1) cytokine profile to a Th2 profile, which favors virus induced pathogenesis and survival. Pregnancy is also associated with a similar Th2 dominance. In non-pregnant individuals, exposure to psychological or physical stress may be associated with latent herpes viral reactivation and could result in …

Histone Deacetylases As Targets For Melanoma Immunotherapy, David Michael Woods

USF Tampa Graduate Theses and Dissertations

Cancer represents the second leading cause of death in the United States. For many malignancies, currently available treatment options offer little long-lasting survival benefits to patients. However, recent studies have shown immunotherapeutic approaches to be an attractive strategy to cancer treatment. While many current immunotherapeutic strategies convey durable responses, such responses are only seen in a minority of patients. An increased understanding of the mechanisms governing tumor immunogenicity and the biology of immune responses is crucial to improving upon the efficacy of current and future cancer immunotherapies. Histone deacetylases (HDACs), enzymes classically associated with regulation of gene expression, have been …

The Inflammatory Response Initiated By The Spleen To Ischemic Stroke, Hilary Seifert

USF Tampa Graduate Theses and Dissertations

The peripheral immune system plays a role in delayed neural injury after stroke. This response originates from the spleen as splenectomy prior to middle cerebral artery occlusion (MCAO) in rats significantly reduces infarct volume in the brain. This research is based on the hypothesis that inhibiting the splenic response will reduce neurodegeneration after stroke. Studies in animals have implicated lymphocytes as the immune cell type that is detrimental following MCAO. Interferon gamma (IFNγ) has been identified as a pro-inflammatory cytokine that is also detrimental following stroke. IFNγ is important because it activates microglia and macrophages in a pro-inflammatory nature that …

Analysis Of Variable Effects On Presence Of Cryptosporidium Oocysts And Giardia Cysts In Effluent Water From Wastewater Treatment Utilities In Florida From 1998 To 2010, Katherine Jane Barkan

USF Tampa Graduate Theses and Dissertations

The concern of a Cryptosporidium or Giardia waterborne outbreak due to treated wastewater has had water treatment utilities using some of the highest water cleansing technologies available. Cryptosporidiosis and Giardiasis are severe diarrheal diseases which can lead to death, thus it is important that appropriate steps are taken to assure these parasites are not present in the effluent of treated wastewater. This study examined the results of 863 assays for Giardia and Cryptosporidium on the effluent of wastewater treatment facilities and found that county of collection, watershed of collection, and laboratory analyzing the sample have the most significant impact on …

Enhancing The Immune Response Through Ikkbeta-Induced Activation Of Nf-Kappab, Emily Hopewell

USF Tampa Graduate Theses and Dissertations

Nuclear factor-κB (NF-κB) is one of the main regulators of inflammatory and immune responses. It is a family of transcription factors composed of five members: RelA, RelB, cRel, NF-κB1 (p105/p50), and NF-κB2 (p100/p52). Homo- and hetero-dimers of family members are inhibited by inhibitor of &klappaB (IκB) family members and activated by IκB kinase (IKK) family members. The IKK family is comprised of IKKα, IKKΒ, and IKKγ. The focus of my dissertation delves into the role of NF-κB activation by IKKΒ in both an immunotherapy setting and its role in T cell mediated anti-tumor immune responses.

A central focus of immunotherapy …