Molecular Biology Commons^™

Riluzole As A Dual-Targeted Radiosensitizer For Osteosarcoma: Targeting Tumor Cells And Angiogenic Vasculature To Enhance Single High-Dose Radiotherapy Efficacy, Pooja P. Rao

Dissertations, Theses, and Capstone Projects

Osteosarcoma (OS), the most common primary bone malignancy of children and young adults, is intrinsically radioresistant, and outcomes for patients with unresectable or metastatic disease have not improved in over four decades. Single-dose radiation therapy (SDRT) is a potent modality against radioresistant, highly vascularized sarcomas, but its application in OS is constrained by dose-dependent normal tissue toxicity. Radiosensitizers achieving tumor control at lower doses therefore offer a direct route to widening the therapeutic window. Critically, OS radioresistance is not tumor-cell-autonomous. It emerges from two coordinated compartments: aberrant DNA repair and antioxidant capacity intrinsic to the tumor cell, and a radioprotective, …

Evaluating The Effects Of Akt Knockdown And Everolimus Treatment On Ewing Sarcoma, Arisha Arif, Alfie Barcenez, Nicole Vanegas-Riddick

Posters - 2026

The purpose of this study is to use the gene AKT1, due to the interest in AKT1’s role in cancer cell proliferation, and the drug Everolimus, to determine if combined targeted therapy works as a more efficient therapeutic approach. We hypothesize that the knockdown of AKT1 will increase the sensitivity of Ewing sarcoma cells to Everolimus, resulting in reduced proliferation and/or survival compared to drug treatment alone. This would suggest that AKT1 normally protects cells from drug-induced stress. Ewing Sarcoma has been connected to chromosomal translocations and most common in pediatric patients. It is most often treated with chemotherapy and …

Sirna Knockdown Of Rptor Alters Gene Expression In Ewing Sarcoma Cells, Sergio Cipriano, David Leavitt, Michael Oliva, Liam Valdez

Posters - 2026

Ewing sarcoma is a highly aggressive cancer that primarily affects children and young adults. Although treatment options exist, many patients do not respond effectively, showing the need for improved targeted therapies¹. RPTOR is a key in mTORC1 complex which regulates cell growth, proliferation, and survival². LY2874455 is a selective pan-FGFR inhibitor that targets growth factor signaling pathways involved in tumor progression³, and FGFR signaling interacts with pathways such as mTOR, making it a potential target for combination therapies. We hypothesized that silencing RPTOR in Ewing sarcoma cells would disrupt mTOR signaling and alter expression of genes linked to cell survival …

Sox18 Unleashed Exploring The Transcriptomic Landscape - Differential Gene Expression Analysis Via Rna Seq In Overexpressed Sox18, Van Nguyen, Kahlie Hernandez, Monabelle Elbayeh

Posters - 2026

Cancer remains a leading cause of death worldwide, and childhood sarcomas such as Rhabdomyosarcoma (RMS) and Ewing Sarcoma (ES) are particularly aggressive with limited targeted treatment options. Despite advancements in cancer therapies, metastatic sarcomas still have a survival rate below 30%, emphasizing the need for new therapeutic targets. SOX18, a transcription factor has played a role in vascular development and endothelial differentiation, functioning as a key driver of angiogenesis. In cancer, increased SOX18 expression has been linked to dysregulated cell migration, invasion, and therapy resistance mechanisms. However, the extent to which SOX18 influences RMS and ES at the transcriptional level …

An Antioxidant Cocktail Of Tert-Butylhydroquinone And A Manganese Porphyrin Induces Toxic Levels Of Oxidative Stress In Cancer Cells, Sandra Tamarin, Hannah Jung, Joseph Lamorte, Laura Biesterveld, Gabriel Piñero, Grace Turchetta, Molly Myers, Rebecca Oberley-Deegan, Aimee Eggler

Student Papers, Posters & Projects

Despite significant advancement in cancer treatments, therapies with minimal toxicity to healthy cells are still limited. One targetable weakness of cancer cells is their sensitivity to oxidative stress. We find that the combination of two antioxidants—the common food additive tert-butylhydroquinone (tBHQ) and a manganese porphyrin in clinical trials, MnTnBuOE-2-PyP5+ (MnBuOE)—increases oxidative stress and causes apoptotic death in several cancer cell lines, but not in mouse primary fibroblasts. Investigating the mechanism of cell death, MnBuOE is observed to catalyze the oxidation of tBHQ, producing the electrophilic quinone tert-butylquinone (tBQ). A critical role for tBQ and its electrophilic character was revealed with …

Bifunctional Fusion Protein Pdl1sfv/Micae For Cancer Immunothearpy, Junyi Li

All Dissertations

Cancer immunotherapy has highlighted the importance of immune checkpoint blockade and innate immune cell engagement in battling tumor-mediated immune suppression in the past few decades. However, with cancer development, advanced tumors are often found to develop resistance towards single-target immunotherapy due to the complexity of the immunosuppressive mechanisms within the tumor microenvironment (TME). To address this, we developed a novel bifunctional fusion protein, PDL1sFv/MICAe, which combines the tumor-targeting capability of an anti-PDL1 single-chain variable fragment (sFv) with the NK cells immunostimulatory properties of the MICA extracellular domain.

In vitro functional assays revealed that PDL1sFv/MICAe significantly enhanced cytotoxicity towards natural killer …

Why Acromegaly Dies: A Systematic Review, Isam Noori Salman, Safaa Ehssan Atta, Baydaa Ahmed Abed, Noor Ulhuda G. Mohammed

Maaen Journal for Medical Sciences

Acromegaly is a rare endocrine clinical syndrome characterized by long-term elevated production of growth hormone (GH) due to a pituitary adenoma tumor. The main problem of acromegaly patients (AC-PTs) is prolonged elevated GH concentration, which leads to increased insulin-like growth factor 1 (IGF-1) production, causing the characteristic tissue and bone overgrowth. The appearance of diabetes in AC-PTs was linked with the high risks of cardiovascular morbidity, indicating that individuals with both conditions face heightened health challenges. Acromegaly typically has a higher cancer incidence rather than the general population. Without early diagnosis and effective treatment, excess GH can have widespread systemic …

Examining The Molecular Mechanisms Of Glucagon-Like Peptide-1 Receptor Agonists In Cancer Cell Biology, Oliver G. Sabet

Honors Scholar Theses

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are synthetic analogs of glucagon-like peptide-1 (GLP-1) used to treat obesity and diabetes by reducing blood glucose levels and appetite. While early rodent studies suggested a link between GLP-1RAs and thyroid cancer pathogenesis, evidence in humans remains inconclusive, with randomized controlled trials not supporting that link. Due to the rapid, widespread use of these drugs, concerns have expanded to other obesity-associated cancers, with conflicting findings on their role in cancer progression. With this contradictory evidence in a novel intersection of obesity medicine and oncology, this literature review aims to summarize current understandings between GLP-1-RAs and …

Multiscale Integration Of Receptor-Ligand Dynamics Into Discrete And Continuous Tumor Growth Models With Application To Tyrosine Kinase Inhibitor Treatment, Romasa Qasim

Open Access Theses & Dissertations

The epidermal growth factor (EGF) receptor cascade plays a crucial role in the survival and proliferation of tumor cells. Tyrosine kinase inhibitors (TKIs) are a class of drugs that inhibit epidermal growth factor receptors (EGFRs), thereby preventing the downstream signal transduction. Despite their importance, models that link spatial receptor dynamics to tumor growth remain scarce. Further, TKIs act through selective mechanisms, inhibiting active, inactive, or all receptor states, which poses a challenge to traditional modeling approaches.

We propose to numerically study two mathematical models incorporating receptor-dynamics into cancer models to describe the impact of EGFR overexpression and TKIs. The first …

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

Investigation Of The Effects Of The Peptidylarginine Deiminase Inhibitor Cl-Amidine On Apoptosis And Gene Expression In Ovarian Cancer, Victoria Walden

Longwood Senior Thesis Proposal

Peptidylarginine deiminases (PADs) are a family of enzymatic proteins responsible for the conversion of arginine and methylarginine residues to citrulline. This conversion is important for several key cellular processes including transcriptional gene regulation. Recently, a link has been established between overexpression of a particular PAD, PAD4, and the accelerated progression of both autoimmune diseases and cancers. Ovarian cancer exhibits heightened levels of PAD4 in affected cells. High levels of PAD4 are associated with the formation of neutrophil extracellular traps (NETs) that promote cancer metastasis, and downregulation of the p53 apoptotic pathway. Thus, it is important to explore inhibitors of PAD4. …

Steroid Receptors And Coregulators: Dissemination Of Sex Differences And Emerging Technologies, Sally Pauss, Evelyn A. Bates, Genesee J. Martinez, Zane T. Bates, Zachary A. Kipp, Cassandra D. Gipson, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Steroid receptors are ligand-induced transcription factors that have broad functions among all living animal species, ranging from control of sex differences, body weight, stress responses, and many others. Their binding to coregulator proteins is regulated by corepressors and coactivators that interchange upon stimulation with a ligand. Coregulator proteins are an imperative and understudied aspect of steroid receptor signaling. Here, we discuss steroid receptor basics from protein domain structures that allow them to interact with coregulators and other proteins, their essential functions as transcription factors, and other elemental protein–protein interactions. We deliberate about the mechanisms that coregulators control in steroid receptor …

Characterizing And Targeting The Non-Catalytic Functions Of Phosphatase Of Regenerating Liver 3 (Prl-3) In Oncogenesis And Cancer Progression, Jeffery T. Jolly

Theses and Dissertations--Molecular and Cellular Biochemistry

Phosphatase of Regenerating Liver 3 (PRL-3) is frequently upregulated in various cancers and is associated with poor patient prognosis. Although traditionally studied for its phosphatase activity, PRL-3 also interacts with the CNNM family of magnesium transporters through its catalytic site, and these two functions are mutually exclusive at any given time. Most previous studies relied on a commonly used PRL-3 mutation that disrupts both phosphatase activity and CNNM binding, making it challenging to determine which function drives its oncogenic effects. To address this gap in the field, I utilized a panel of PRL-3 mutants that selectively disrupt either phosphatase activity …

The Role Of Fbxl16 In Regulating Erk3 Stability And Cell Migration, Seth Charles Murdock

Browse all Theses and Dissertations

Extracellular signal-regulated kinase 3 (ERK3) is a member of the atypical mitogen-activated protein kinase (MAPK) family. While ERK3’s role in promoting cell migration and invasion in multiple types of cancer has been well-documented, its activation and regulation remain poorly understood. Unlike other typical MAPK proteins, whose activation is regulated via the phosphorylation of an upstream kinase, ERK3 is regulated through its abundance, as it is constitutively phosphorylated when present in the cell. While USP20 has been established as a deubiquitinating protein that stabilizes ERK3 by preventing its degradation, both TRIM21 and FBXW7 have been identified as E3 ligases that target …

Investigating Mono-Driver Versus Multi-Driver Oncogenesis Via Alterations To Cell Signaling Pathways, Abygail Chapdelaine

Open Access Dissertations

The latest edition of Global Cancer Statistics released by the American Cancer Society reported approximately 20 million newly diagnosed cancer cases worldwide in 2022 with 9.7 million deaths. This ranks cancer as the second leading cause of death worldwide. For the majority of cancer patients, the standard treatment approach is chemotherapy and/or radiation therapy, and while this has been successful in some patients, a lack of specificity to cancer cells causes severe side-effects when these agents damage healthy cells. Despite extensive efforts that have gone into developing targeted cancer therapeutics that block functions specific to cancer, they have not been …

Characterizing Mechanisms Of Dna Repair And Genome Stability, Joshua Turner

All Dissertations

Every day our cells are bombarded with DNA lesions that threaten the stability of our genome. To help maintain genomic integrity our cells evolved to have a network of enzymes dedicated to repairing DNA lesions. Upon encountering a site of DNA damage, a cell recruits enzymes that remodel the stalled replication fork by reannealing the newly synthesized DNA together known as fork regression. Loss of fork regression activity has been shown to promote replication stress resistance after induced DNA damage. In this thesis, I discuss the role F-Box Helicase 1 (FBH1) plays in fork regression and how FBH1 promotes the …

Interleukin 24 Induces Apoptosis Through Glycogen Synthase Kinase-3 Beta Inactivation In Prostate Cancer Cells, Sual J. Lopez, Moira Sauane

Theses and Dissertations

Interleukin 24 (IL-24) is a tumor-suppressing protein currently in clinical trials. IL-24 induces cancer-specific apoptosis by activating endoplasmic reticulum (ER) stress and mitochondria dysfunction. We have previously demonstrated that IL-24 leads to apoptosis in cancer cells by protein kinase A (PKA) activation in human breast cancer cells. To further understand the mechanism by which IL-24 induces apoptosis, I analyzed the role of glycogen synthase kinase-3 (GSK3), a highly conserved and normally active serine/threonine kinase in cancer cells and downstream target of PKA. The work reported here provides direct evidence that GSK3 was inhibited following IL-24 treatment in human prostate cancer …

Decisions, Decisions: Dna Damage Induced Modification Of P53 And The Effect Of Modifications On P53 Differential Binding To The Dna, Savannah Gabrielle Keating

Theses and Dissertations

p53 is the most frequently mutated tumor suppressor protein in cancer. It is highly regulated, most often via post-translational modifications (PTMs). Different pathways and target genes are differentially activated by p53 and there is much left to understand how this occurs. The regulation of p53 at the post-translational level is incredibly important to its DNA damage response, and, therefore, it is understood that PTMs are often involved in the differential activation of pathways by p53. This project aimed to identify some of the types and locations of post-translational modifications on p53 in response to different modes of DNA damage with …

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, …

Using Rapid Protein Degradation To Determine The Effect Of Runx1 Loss-Of- Function On Dna Damage Accumulation And Repair., Jackriel Pina Morales

Theses and Dissertations

Germline mutations in RUNX1 are associated with familial platelet disorder with a predisposition to myeloid malignancy (RUNX1-FPDMM), in which patients present with low platelet counts,excessive bleeding and bruising, and an increased risk of Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS) development throughout their lifetime. To understand how these loss-of-function mutations in RUNX1 drive predispose to malignancy, it is important to develop a detailed understanding of the molecular basis of RUNX1 function. While RUNX1 is a transcription factor, preliminary data from our group and work from others suggests that RUNX1 also interacts with proteins that are critical for DNA damage …

The Role Of The Cdk8 Kinase Module In Maintaining Proteostasis, Stephen Willis

Theses and Dissertations

The underlying etiology of numerous disease states results from perturbations in the maintenance of cellular proteostasis. Carcinogenesis relies on these perturbations to foster uncontrolled cell growth and eventual metastases, while neurodegenerative diseases are a consequence of such perturbations. Control of these processes occurs at numerous molecular levels, commonly starting with transcription. A key transcriptional complex that is involved is the CDK8 Kinase Module (CKM). The CKM is conserved from yeast to man, forming a tetrameric complex consisting of MED12, MED13, CDK8, and CCNC. The CKM has not only been implicated in a variety of cancers but also in a spectrum …

Rps6kb1 Is A Critical Target For Overcoming Tumor Lineage Plasticity And Therapy Resistance, Saptadwipa Ganguly

Theses and Dissertations--Toxicology and Cancer Biology

Most tumors initially respond to treatment, yet refractory clones subsequently develop owing to resistance mechanisms which can be classified as intrinsic or extrinsic resistance. The intrinsic resistance is usually present prior to any treatment whereas the extrinsic resistance develops as a result of exposure to some kind of therapy. In order to target these “therapy resistant” tumor cells an unbiased screen of an FDA-approved drug library against cancer cells was performed. This was followed by synthesis of chemical analogs of the most effective drug.

The studies led to the identification of a derivative of the antihistamine drug ebastine, designated Super-ebastine …

Characterization Of Trafficking And Metabolic Functions Of The Endocytic Regulator Ehd1 In Ewing Sarcoma, Sukanya Chakraborty

Theses & Dissertations

Ewing sarcoma (EWS) is the second most common bone malignancy in children and adolescents. Despite improvement in survival due to advances in multimodality treatment strategies, patients with metastatic or recurrent disease have very poor outcomes. Overexpression of the EPS15 Homology Domain containing 1 (EHD1) protein has been linked to tumorigenesis but whether its core function as a regulator of intracellular traffic of cell surface receptors plays a role in oncogenesis remains unknown.

Studies presented in this dissertation establish that EHD1 overexpression is a feature of nearly 90% EWS patient tumors with high EHD1 expression specifying shorter patient survival. ShRNA-knockdown and …

Challenges In Genetic Counseling In Hereditary Cancer Syndromes In A Mexican Oncologic Center, Diana Cristina Perez-Ibave, Diana Cristina De Lourdes Perez Ibave, María Fernanda Noriega-Iriondo, Omar Alejandro Zayas-Villanueva, Fernando Alcorta-Nuñez, Juan Francisco González-Guerrero, Adelina Alcorta-Garza, David Hernandez-Barajas, Oscar Vidal-Gutierrez, Carlos Horacio Burciaga-Flores

Research Symposium

Background: In Mexico, hereditary cancer is underdiagnosed, medical geneticists give genetic counseling, but the access is limited due to the socio-economic characteristics of the population. The CUCC (Centro Universitario Contra el Cáncer) Early Cancer Detection Clinic (CECIL) created a model in which patients without cancer are enrolled in a prevention cancer screening program.

Methods: From 2016 to 2021, 3014 patients were enrolled in the prevention program. Patients were evaluated with a hereditary cancer risk survey before a consultation. Those with at least one familial hereditary risk positive answer were assessed in a consultation. We also included patients with cancer diagnoses …

The Roles Of Estrogen Receptor Alpha-Interacting Rnas And Exosomes In Breast Cancer, And E-Cadherin In Carcinomas, Brihget Catalina Sicairos-Meza

Graduate Theses and Dissertations

Carcinomas are malignancies of epithelial cells and account for >80% of cancer-related deaths. Approximately 75% of breast cancers express estrogen receptor alpha (ERα). ERα promotes breast cancer progression by enhancing cancer cell proliferation. Tamoxifen is commonly used to treat ERα-positive breast cancers but can result in endocrine therapy resistance. The mechanisms underlying endocrine therapy resistance remain elusive. The Du lab recently found that ERα is an RNA-binding protein. However, the significance of the ERα-RNA interaction is unknown. We fractionated ERα-positive MCF7 cells into cytoplasmic and nuclear fractions, followed by immunoprecipitation of ERα with associated RNAs and RNA-sequencing. We identified many …

Development And Biological Evaluation Of Selective Small-Molecule Inhibitors Of The Human Cytochrome P450 1b1, Austin Hachey

Theses and Dissertations--Chemistry

The human cytochrome P450 1B1 (CYP1B1) is an emerging target for small- molecule therapeutics. Several solid tumors overexpress CYP1B1 to the degree that it has been referred to as a universal tumor antigen. Conversely, its expression is low in healthy tissues. CYP1B1 may drive tumorigenesis through promoting the formation of reactive toxins from environmental pollutants or from endogenous hormone substrates. Additionally, the expression of CYP1B1 in tumors is associated with resistance to several common chemotherapies and with poor prognoses in cancer patients. However, inhibiting CYP1B1 with small molecules has been demonstrated in cellular and murine model systems to reverse this …

Identification Of Novel Biosynthetic Gene Clusters Encoding For Polyketide/Nrps-Producing Chemotherapeutic Compounds From Marine-Derived Streptomyces Hygroscopicus From A Marine Sanctuary, Hannah Ruth Flaherty

Honors Theses and Capstones

Nearly one out of six deaths in 2020, around ten million people, were caused by cancer, making it a leading cause of death worldwide (WHO, 2022). This major public health issue, in addition to the rise of multidrug-resistant (MDR) pathogens, provides a high demand for the discovery of new pharmaceutical drugs to be used clinically to treat these conditions. The Streptomyces genus accounts to produce 39% of all microbial metabolites currently approved for human health, indicating its potential as an important species to study for antimicrobial and anticancer agents. The long linear genome of Streptomyces contains specialized sequences known as …

Investigation Of Mechanical Regulation On Stat3 Activity And Mmp Production, Jaxson R. Libby

Honors Theses and Capstones

Transcription factor, STAT3, is inappropriately expressed in cancer cells, and has contrasting activation in 2D versus 3D microenvironments. 2D plates are often used for drug screening and do not always recapitulate in vivo responses. To combat inaccurate 2D drug studies, a 3D hydrogel was created to support the growth of cancer cells into a tumor-like environment. The hydrogel consists of a biocompatible dextran homopolysaccharide, cell adhesion RGD sequences, and crosslinker MMP labile peptides. A pH dependent reaction couples the RGD sequences to dextran then the polymers are crosslinked into a gel. Crosslinking is accomplished using terminal cysteine peptide sequences, allowing …

Protacs – A Novel And Rapidly Developing Field Of Targeted Protein Degradation, Hannah R. Gatley

Theses and Dissertations

There is a continued need for new technology and strategies for tackling cancer and other diseases, and within the current century a novel therapeutic strategy has emerged in the realm of targeted protein degradation called Proteolysis-Targeting Chimeras (PROTACs). This technology specifically targets and degrades disease-causing proteins via the ubiquitin-proteasome system, and has seen an explosion of research and intrigue in both academia and industry over the past two decades. The diversity of PROTAC classes based on the E3 ligase recruiting ligand and the target protein allows for a universal molecular structure that can be customized for a specific target and …

Exploring The Anticancer Mechanism Of Thienopyrazole Derivative Tpz-1 In Acute Myeloid Leukemia, Jessica Dyanne Hess

Open Access Theses & Dissertations

Anticancer drug discovery is a time and resource-consuming process for which exceedingly reliable and efficient modern approaches are needed. Phenotypic drug screenings can generate highly potent and innovative drug candidates; however, deconvolution of the drugâ??s target often presents significant barriers to drug development. To overcome this hurdle, we have originally combined in vitro and in silico analyses to uncover the molecular mechanism(s) driving the anticancer activity of the uniquely structured small molecule drug candidate, Tpz-1. Our study revealed that Tpz-1 is a multitargeted agent which induces the programmed death of HL-60 acute myeloid leukemia cells primarily through disruption of microtubule …