Medicine and Health Sciences Commons^™

Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation And Progression, Janine M. Deblasi

USF Tampa Graduate Theses and Dissertations

NRF2 is a redox-responsive transcription factor the directs the antioxidant program and several critical metabolic processes. Mutations in NRF2 or its negative regulator KEAP1 occur in up to one third of non-small cell lung cancers (NSCLCs) and are often associated with resistance to therapy and poor outcomes. In the present studies, murine alleles of the Keap1 and Nrf2 mutations found in human NSCLC were developed and I comprehensively investigated their impact on tumor initiation and progression. I observed that chronic Nrf2 stabilization by Keap1 loss-of-function or Nrf2 activating mutation was not sufficient to cause lung tumor initiation, even when p53 …

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 …

Pamam- Cyclodextrin Conjugate Upregulates Brain-Derived Neurotropic Factor In Arpe-19 Cells, Gopika Ashokan

USF Tampa Graduate Theses and Dissertations

Background: Traumatic Brain Injury (TBI) is a major contributor to death and disability due to motorvehicle accidents, sports, physical abuse, and battlefield injuries. The primary insult to the brain leads to inflammation, vascular dysfunction, and oxidative stress in the brain as well as in the eye. This leads to loss of Retinal Ganglion Cells (RGCs) and downregulation of Brain derived Neurotopic Factor (BDNF). BDNF is a neurotrophic factor that binds to Tropomyosin Receptor Kinase B (TrkB) receptor to promote cell growth, survival, and differentiation. Current treatment strategies do not promote neuronal regeneration. Therefore, novel treatments are needed to restore vision …

How Some Arboreal Salamanders (Genus Aneides) Jump, Glide, And Generate Lift, Christian E. Brown

USF Tampa Graduate Theses and Dissertations

The jumping and subsequent aerial behaviors of arboreal lungless salamanders (genus Aneides) had never been investigated or described. The aims of this research were to (1) compare jumping performance within the family Plethodontidae with a special focus on arboreal species from genus Aneides, (2) describe the biomechanics and kinematics of aerial behaviors after a jump or extended fall, and (3) model airflow over the morphology of the most aerially adept salamanders to investigate if they are capable of generating lift. First, I recorded salamanders jumping, locomoting vertically, dropping, and flying in a vertical wind tunnel. Then, I laser-scanned and reconstructed …

Diet And Salivary Microbiome On Cardiovascular Risk And Glycemic Control In Participants With And Without Type 1 Diabetes: The Cacti Study, Tiantian Pang

USF Tampa Graduate Theses and Dissertations

Introduction: The prevalence of type 1 diabetes mellitus (T1DM) has been increasing drastically in the United States. People with T1DM are at a higher risk of developing diabetes-related complications, including cardiovascular disease (CVD). Diet is one of the most modifiable factors and healthy eating could reduce CVD risk among individuals with T1DM. The current 2015-2020 Dietary Guidelines for Americans focus on overall healthy eating patterns rather than individual foods and nutrients. A healthy dietary pattern or high-quality diet can be measured by diet quality indexes, and generally contains minimal ultra-processed foods (UPF). Although substantial evidence has linked poor diet quality …

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, …

Apkcs Role In Neuroblastoma Cell Signaling Cascades And Implications Of Apkcs Inhibitors As Potential Therapeutics, Sloan Breedy

USF Tampa Graduate Theses and Dissertations

Neuroblastoma (NB) is a cancer that develops in the neuroblasts. It is the most common cancer in children under the age of 1 year, accounting for approximately 6% of all cancers. The prognosis of NB is linked to both age and degree of cell differentiation. This results in a range of survival rates for patients, with outcomes ranging from recurrence and mortality to high survival rates and tumor regression. Our previous work indicated that PKC-ι promotes cell proliferation in NB cells through the PKC-ι/Cdk7/Cdk2 cascade. We report on two atypical protein kinase inhibitors as potential therapeutic candidates against BE(2)-C and …

Using The Genetic Counseling Skills Checklist To Characterize Prenatal Genetic Counseling, David A. Cline

USF Tampa Graduate Theses and Dissertations

Genetic Counseling relies on communication skills to help patients understand and adapt to a genetic disease or risk. However, little is known about which skills are most commonly used or the extent to which genetic counseling sessions vary. A novel process measure titled the "Genetic Counseling Skills Checklist" (GCSC) was developed in a prior pilot study and includes 8 broad categories each consisting of 5-8 skills. This study is the first to apply the final GCSC to characterize 20 mock prenatal sessions conducted by 5 genetic counselors (GCs) for 2 prenatal indications using 3 trained actors as patients. Two experienced …

A Holistic Investigation Of Acidosis In Breast Cancer, Bryce Ordway

USF Tampa Graduate Theses and Dissertations

In the early 20th century, Nobel laureate Otto Warburg made the observation that cells of a carcinoma had considerably higher glycolytic metabolism and considerably lower oxidative metabolism compared to cells of a normal tissue. He postulated that within this observation was the key to deciphering the differences between malignant and normal tissue. It is now well established that tumors of the breast are unequivocally acidic, caused by an abnormal amount of aerobic glycolysis, colloquially known as the Warburg effect. Over the last decades, our group, led by Dr. Robert J. Gillies, has set out to characterize the causes and consequences …

Inaccuracies In Patient Self-Report Of Genetic Testing Results For Hereditary Cancer Risks Could Impact Risk-Management Practices, Brittany Faye Sears

USF Tampa Graduate Theses and Dissertations

Pathogenic variants (PV) or likely pathogenic variants (LPV) in a cancer risk gene increase lifetime risks of developing cancer. National guidelines provide evidence-based recommendations on cancer risk management (CRM) strategies tailored to the cancer risks associated with PV/LPV in different genes. Emotional responses after learning of a PV/LPV have been studied as predictors of patient adherence to CRM, but less attention has been given to whether patients remember their actual genetic test results and the impact this may have on subsequent adherence to CRM. We surveyed a group of 114 participants registered with the Inherited Cancer Registry (ICARE), all of …

Role Of Bmi1 In Acute Lung Injury, María Helena Hernández-Cuervo

USF Tampa Graduate Theses and Dissertations

Acute Lung Injury (ALI) is a set of signs and symptoms that lead to acute hypoxemic respiratory failure characterized by bilateral pulmonary infiltrates not attributed to cardiogenic origin. It is caused by a massive innate immune response, with the migration of white blood cells (neutrophils and macrophages principally) and a cytokine storm, followed by alterations in mitochondrial function, increase in reactive oxygen species production, and oxidative stress that in turn induces more mitochondrial damage. Several studies have shown that mitochondrial alterations are key events in the mechanism of ALI and reducing mitochondrial dysfunction could be a possible target in the …

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 …

Using Artificial Intelligence To Decipher Epigenetic Code Of Drug Resistance In The Deadliest Human Malaria Parasite, Samira Jahangiri

USF Tampa Graduate Theses and Dissertations

Malaria remains one of the immense global public health challenges, with an estimated ~200 million cases worldwide in 2019 despite the remarkable gains in reducing this deadly disease over the past decade. The recent emergence and spread of artemisinin resistance (ART-R) in Plasmodium falciparum will increasingly impede global efforts to control and eliminate malaria. Previous studies have observed broad transcriptional changes and identified several noncoding genetic variants strongly associated with ART-R. The broad transcriptional variations suggest that the malaria parasite uses sophisticated epigenetic regulation to survive under drug pressure. Therefore, evaluating the regulatory effects of noncoding-variants in malaria parasites is …

Moving In Fluid: Exploring How Fishes Manipulate Water To Swim Efficiently, Nils B. Tack

USF Tampa Graduate Theses and Dissertations

Moving through a dense fluid such as water presents some unique challenges to minimizing energy use and maximizing performance (i.e., speed). Due to animal-fluid interactions during swimming (drag and thrust production) fish have evolved a variety of morphological structures and locomotor mechanisms. For instance, fish rely on body bending and/or fins to interact with the surrounding water such that energy can be transferred to generate thrust. Typically, this synergy promotes morphologies and behaviors aimed at enhancing propulsive efficiency and/or minimizing metabolic activity to lessen the cost of transport (COT). This work focuses on quantifying the energetic and hydromechanical benefits of …

Exercise Prescription Practices In University Counseling Centers: Testing The Information-Motivation-Behavioral Skills Model, A'Naja M. Newsome

USF Tampa Graduate Theses and Dissertations

The co-occurence of physical inactivity and poor mental health in the college student population can lead to chronic health issues that have negative short-term (e.g., academic success and weight gain) and long-term (e.g., obesity, serious mental illness, and premature mortality) impacts. Integrating exercise prescription into the mental health treatment plan of college students could enhance the holistic care model described by The American College Health Association (ACHA) and Healthy Campus task force. Understanding the knowledge, attitudes, and skills that mental health professionals (MHPs) hold regarding exercise prescription is important for policy formation and program development for college student health. The …

Synthesis Of A Multimodal Ecological Model For Scalable, High-Resolution Arboviral Risk Prediction In Florida, Sean P. Beeman

USF Tampa Graduate Theses and Dissertations

West Nile virus (WNV) and Eastern Equine Encephalitis virus (EEEV) represent the two greatest endemic arboviral risks to the state of Florida. Currently, no approved human vaccine exists for the prevention of either virus. In the absence of a vaccine, effective disease surveillance is paramount for public health. In Florida, WNV and EEEV sentinel chicken surveillance is conducted by mosquito control programs operated at the county, municipality, or special taxing district level. This program was implemented in 1978 following human outbreaks of St. Louis Encephalitis virus (SLEV) that occurred between 1959 and 1977, with initial sentinel coops placed in proximity …

Evolution Of Targeted Therapy Resistance In Eml4-Alk Positive Non-Small Cell Lung Cancer, Robert Vander Velde

USF Tampa Graduate Theses and Dissertations

Targeted therapies have emerged as potent treatments that lead to the remission of many tumors. However, they rarely cure cancers in advanced, metastatic settings. This is due to the evolution of resistance, which in turn can be ascribed to the survival of small subpopulations of tolerant and/or resistant cells. Here we investigated the evolution of resistance to EML4-ALK inhibitors in non-small cell lung cancer (NSCLC) and demonstrated that resistance evolves gradually, from unique pre-treatment sub-populations, as multiple resistance mechanisms accumulate in a Darwinian fashion. Despite accumulating multiple changes, cells evolved, in parallel, toward similar inhibitor specific phenotypes. Evolving cells have …

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 Distribution In Native Populations From Mexico And Central America Of The C677t Variant In The Mthfr Gene, Lucio A. Reyes

USF Tampa Graduate Theses and Dissertations

Objectives: To explore evolutionary hypotheses for the high frequencies of a substitution in the methylenetetrahydrofolate reductase (MTHFR) gene, in Mexican and Central American Indigenous populations.

Materials and methods: We obtained allele frequencies for the C677T variant in the MTHFR gene and ecological information for 37 indigenous samples from Mexico and Central America. We calculated Hardy–Weinberg equilibrium and computed Fst statistics. We computed correlations between the samples' allele frequencies and ecological and geochemical variables.

Results: Many of the samples have extremely high frequencies of the T allele (q̄ = 0.62, median = 0.66). In this region, the frequency of the T …

Microbiological Study In A Gneissic Cave From Sri Lanka, With Special Focus On Potential Antimicrobial Activities, Ethige Isuru P. Silva, Pathmakumara Jayasingha, Saman Senanayake, Anura Dandeniya, Dona Helani Munasinghe

International Journal of Speleology

The emergence of antibiotic resistance is a global health crisis, thus the search for novel antimicrobial compounds has become a continuous necessity. Underexplored and extreme environments, such as cave ecosystems, have been identified as a promising potential source for the discovery of novel microorganisms with novel antimicrobial compounds (AMC). This study presents the first cave microbiological investigation in Sri Lanka, with a special preference for bioprospecting of novel AMC. The cave sediment characterization demonstrated the presence of close to strong acidic conditions (pH 3.1 – 3.3) and thus indicates the possibility of isolating acidophilic microorganisms. Eight cave wall/ceiling fungal strains …

Bone Microenvironmental Control Of Skeletal Malignancy, Chen Hao Lo

USF Tampa Graduate Theses and Dissertations

Bone is a common site of metastasis for many solid malignancies. Bone-metastatic cancers pose a significant clinical problem worldwide and is among the main causes for cancer patient morbidity and mortality. Patients with advanced bone-metastatic diseases often present with either osteolytic or osteogenic bone diseases as their cancers progress. These bone pathologies are products of the cancer co-opting the local bone remodeling stroma to yield important growth nutrients and factors. Unfortunately, skeletal metastases remain incurable and are fatal. Identifying and understanding the causal multicellular and molecular interactions underlying skeletal malignancies can yield crucial ideas for targeting and inhibiting disease progression. …

Spatial And Temporal Determinants Associated With Eastern Equine Encephalitis Virus Activity In Florida, Kristi M. Miley

USF Tampa Graduate Theses and Dissertations

Eastern Equine Encephalitis virus (EEEV) is considered the most pathogenic mosquito-borne illness in the United States. Human mortality has been estimated to range between 35 to 75%, with horses experiencing mortality rates greater than 90%. A large number of EEEV cases occur in Florida. Though we have come a long way since the first human infection was identified in the 1930s, there is still much to learn regarding the virus’s ability to maintain transmission year-round in Florida. Phylogenic studies support that Florida may serve as the geographic reservoir for EEEV. This research investigated spatiotemporal and ecological variables associated with risk …

Functional Gait Asymmetries Achieved Through Modeling And Understanding The Interaction Of Multiple Gait Modulations, Fatemeh Rasouli

USF Tampa Graduate Theses and Dissertations

Walking is an important determinant of human functionality. Gait disabilities affect millions of people worldwide every year. Investigating the science of walking advances recovery techniques and assistive devices for gait rehabilitation. A functional gait promotes productivity, independence, and quality of life. Human gait, like any other moving mechanism, is a dynamic system. Understanding and analyzing the dynamic aspects of gait improves the recovery methods to fundamentally affect and interact with lower limbs.

This dissertation aims to fill the gaps in mechanical simulations of gait and dynamic analysis of rehabilitation techniques. The solutions consider kinematic, kinetic, and spatiotemporal parameters of gait …

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 …

Mechanistic And Translational Studies On Skeletal Malignancies, Jeremy Mcguire

USF Tampa Graduate Theses and Dissertations

New treatment strategies are desperately needed for treating skeletal malignancy. Skeletal malignancies can be either primary cancer that originated in the bone, such as osteosarcoma, or metastatic cancer that spread from another organ to the skeleton, as in the case of breast or prostate cancer. In this thesis, I will detail two projects that focus on the discovery of new treatment strategies for both primary skeletal malignancy and metastatic skeletal malignancy.

The first project focuses on the primary skeletal malignancy, osteosarcoma, a rare cancer that is commonly diagnosed in children and young adults and metastasizes to the lungs. The survival …

Hyaluronic Acid Coated Targeted Lipid Micellar Nanoparticle As A Delivery Vehicle For Lapatinib And Ketoconazole In Egfr Mutated Lung Cancer, Nadia Tasnim Ahmed

USF Tampa Graduate Theses and Dissertations

Background: According to the American Cancer Society, lung cancer was accountable for over 142,000 deaths in the USA in 2019. Common mutations related to lung cancer mainly occur in TP53, EGFR, and KRAS genes. Lapatinib is a small molecule tyrosine kinase inhibitor which acts reversibly on both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). Overexpression of EGFR leads to increased production and signaling of proteins that cause upregulation of cellular proliferation, cholesterol synthesis and resistance to apoptosis. Ketoconazole is an imidazole antifungal agent which works principally by inhibiting the enzyme cytochrome P450 14α-demethylase (CYP51A1) …

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 …