Cancer Biology Commons^™

Design, Syntheses And Biological Applications Of Fluorescent Probes For Nad(P)H, Hsa And Cellular Microenvironment Sensing, Adenike M. Olowolagba

Dissertations, Master's Theses and Master's Reports

Fluorescent probes have emerged as powerful tools for investigating complex biological processes due to their high sensitivity, selectivity, and capability for real-time, non-invasive imaging. In particular, the detection of key biomolecules such as NAD(P)H, viscosity-related parameters, human serum albumin (HSA), and pH is essential for understanding cellular metabolism, redox homeostasis, and disease progression. In Chapter 2, three coumarin-based fluorescent probes (A–C) were designed, synthesized, and characterized for monitoring NAD(P)H levels in living cells. Probes A and B feature coumarin–cyanine hybrid structures linked via vinyl and thiophene bridges to 3-quinolinium acceptors, respectively, while probe C incorporates a dicyano moiety to replace …

Comparative Spatial Biology: A Cross-Species Analysis Of Canine Oral Cancers As Models For Human Disease, Ram Pradhyumnan

Honors Undergraduate Theses

Oral squamous cell carcinoma (OSCC), one of the most common malignancies of the oral cavity, remains a clinically challenging disease due to its aggressive behavior, late-stage diagnosis, and limited improvements in therapeutic outcomes over recent decades. A significant barrier to progress in OSCC research and treatment is the lack of suitable preclinical models that recapitulate the complexity and natural progression of the disease. Most current models—including cell lines, xenografts, and genetically engineered mice—fail to capture key features such as the spatial organization of tumor epithelium, interactions with an intact immune system, and the stepwise evolution from normal mucosa to invasive …

Antiestrogens As Bone Protective Therapeutics For Estrogen Receptor-Positive Breast Cancer In The Presence Of Osteoporosis, Faith E. Parker, Emily K. Zboril, David C. Boyd, Rachel Myrick, J. Chuck Harrell

Undergraduate Research Posters

Breast cancer (BC) is one of the most significant causes of mortality among women and the second leading cause of cancer death in women. The estrogen receptor (ER) is a key oncogenic driver in the majority of breast cancer. ER+ BC is the most common molecular subtype of BC. Management of ER+ breast cancer varies depending on menopausal status. For premenopausal women, the goal is to suppress estradiol production from the ovaries with surgical oophorectomy and/or aromatase inhibitors. In postmenopausal women, endocrine therapy (ET) serves to suppress estradiol production from sources other than the ovaries. During the menopausal transition, estradiol …

Investigation Of Genx Exposure To Pathways Associated With Colorectal Cancer Risk, Emily J. Ferguson

Theses and Dissertations--Toxicology and Cancer Biology

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants widely detected in drinking water and food sources, resulting in chronic human exposure. Among these compounds, hexafluoropropylene oxide dimer acid (HFPO-DA), commonly known as GenX, has been introduced as a short-chain replacement for legacy PFAS such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Although GenX is believed to be a safer alternative, emerging research suggests it can still affect human health.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related death in the United States, highlighting the need to better understand environmental …

Uncovering The Mechanism Of Reep2-Mediated Emt-Driven Membrane Trafficking In Lung Adenocarcinoma, Kevin Fulp

Theses and Dissertations--Toxicology and Cancer Biology

Membrane trafficking is frequently disrupted during cancer progression, and the underlying mechanisms remain largely unknown. Currently, no effective drugs target dysregulated membrane trafficking for cancer treatment. Recent evidence has demonstrated that epithelial-to-mesenchymal transition (EMT) in lung adenocarcinoma (LUAD) employs a membrane trafficking program to coordinate cancer cell invasion and immunosuppression. To further dissect the pro-tumorigenic membrane trafficking program, we initiated an in vivo CRISPRi screen to assess more than 2,000 membrane trafficking-related genes in a syngeneic mouse LUAD model. We identified REEP2, an endoplasmic reticulum (ER) shaping protein, as a novel regulator of EMT-driven membrane trafficking. High REEP2 expression is …

Reep2-Driven Pro-Metastatic Secretion Promotes Lung Cancer Progression, Oluwafunminiyi E. Obaleye

Theses and Dissertations--Toxicology and Cancer Biology

Membrane trafficking plays a critical role in cellular function and is frequently dysregulated in cancer to promote metastasis. In lung adenocarcinoma (LUAD), the epithelial-to-mesenchymal transition (EMT) activating transcription factor, ZEB1, drives a pro-metastatic membrane trafficking program; however, the underlying molecular mechanisms remain poorly understood. Using a CRISPR interference (CRISPRi) in vivo screen of 2,099 membrane trafficking regulators in a syngeneic mouse model of EMT-driven LUAD, we identified REEP2 — an endoplasmic reticulum (ER) shaping protein — as a critical regulator of tumor progression. REEP2 mRNA expression correlates with poor prognosis, EMT signatures, and an immunosuppressive tumor microenvironment in LUAD patients. …

Brief Pulses Of High-Level Fluid Shear Stress Enhance Metastatic Potential And Rapidly Alter The Metabolism Of Cancer Cells, Amanda N. Pope, Devon L. Moose, Guy O. Hudson, Hank R. Weresh, Marion R. Dykstra, Aabha Y. Joshi, Patrick Breheny, Eric B. Taylor, Michael D. Henry

Department of Biomedical and Translational Sciences Faculty Publications

Circulating tumor cells (CTCs) face challenges to their survival, including mechanical and oxidative stresses that are different from cancer cells in solid primary and metastatic tumors. The impact of adaptations to the fluid microenvironment of the circulation on the outcome of the metastatic cascade is not well understood. Here, we find that cancer cells exposed to brief pulses of high-level fluid shear stress (FSS) exhibit enhanced invasiveness and anchorage-independent proliferation in vitro and enhanced metastatic colonization/tumor formation in vivo. Cancer cells exposed to FSS rapidly alter their metabolism in a manner that promotes survival by providing energy for cytoskeletal remodeling …

Determining Genes Involved In Recovery From Chemotherapy In 4t1, Emt6, And Eo771 Breast Cancer Cells, Akash Jagdeesh, Joseph Landry Ph.D.

Undergraduate Research Posters

Breast cancer is one of the most common types of cancer, and often has poor prognosis. Traditional treatments for breast cancer include chemotherapy, which involves a chemical attack on all growing cells within the body. However, these treatments are not 100% effective, and patients might experience recurrence in their cancer months or years after achieving remission. Cancer cells can evade chemotherapy through five mechanisms: senescence, quiescence, cytoprotective autophagy, and apoptosis/necroptosis suppression. Prior studies have conducted CRISPR screens and experiments involving inhibition of epigenetic regulators, to alter the regulation of genes that can contribute to breast cancer chemotherapy resistance. This study …

Synthesis And Characterization Of Succinate Dehydrogenase Inhibitors H2/Z14 And C6/Z96 In Order To Combat Small Cell Lung Cancer, Lauren M. Graves

Honors Undergraduate Theses

The use of ubiquinone inhibitors to combat cancer is a recent development in medicinal science and procedures to efficiently synthesize these drugs remain limited. C6/Z96 and H2/Z14, two succinate dehydrogenase inhibitors, have been previously tested in vitro against NSCLC with positive results. Their similarity to ubiquinone is what makes them a strong candidate for a succinate dehydrogenase inhibitor at the ubiquinone binding site. The heterocyclic scaffolds and substituents are proposed to bind strongly through a combination of electronics, hydrogen-bonding, and fit, allowing them to bind well and prove to be more favorable than ubiquinone when competing for the Q-site. By …

Evaluating Novel Targeted Combination Therapies For Gastrointestinal Cancers, Joseph A. Goode

Graduate Studies Theses and Dissertations 2026

Gastrointestinal (GI) cancers remain among the leading causes of cancer-related mortality worldwide, with therapeutic resistance continuing to limit the effectiveness of current treatments. Three complementary studies were conducted to identify therapeutic vulnerabilities and evaluate novel combination strategies in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC).  First, dual inhibition of fibroblast growth factor receptor 4 (FGFR4) and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling was investigated in PDAC models. A combination of targeted drug treatments reduced viability, clonogenic survival, migration, and suppressed signaling pathways involved in translational control. This supported a functional interaction between FGFR4 and PI3K-mTOR co-activation in …

An Analysis Of Heart Failure Among Cancer Patients In The United States Between 1999 And 2020, Abes A. Bautista Neughebauer, Deepak Talreja, Apostolos Gaitanidis

Department of Medicine Faculty Publications

Background: Cancer and heart failure (HF) are highly prevalent in the population and can co-exist, due to shared risk factors and an aging population. The HF-related mortality burden in cancer patients across in the United States (US) remains poorly understood. The goal of this study is to evaluate the patterns of HF-related deaths among cancer patients in the United States.

Methods: A retrospective analysis was performed using the Centers for Disease Control and Prevention (CDC) WONDER Multiple Cause of Death database between years 1999 and 2020. HF-related deaths were defined as death certificates listing HF as a contributing cause of …

Investigating The Immunostimulatory Potential Of Dsrna-Silk Nanoparticle Complexes In Melanoma, Samuel J. Peters

Theses and Dissertations (Comprehensive)

The rate of resistance to immune checkpoint inhibitor treatment in metastatic melanoma is quite high, with an overall rate of 70%. Melanoma achieves these high rates of resistance by suppressing the immune response in the tumour microenvironment (TME), making them immunologically “cold”. The type 1 interferon response could be leveraged to initiate immune responses in melanoma, making their “cold” TMEs “warm” again. Double-stranded ribonucleic acids (dsRNAs) are potent activators of an innate immune response; however, they are susceptible to degradation by nucleases present in the body and need a carrier. Silk nanoparticles (SNPs) are an ideal drug-delivery platform as they …

Ex Vivo Sensitivity Assays With Molecular Validation To Guide Preclinical Drug Selection For Schwann Cell Tumors, Ethan W. Hass

Graduate Studies Theses and Dissertations 2026

Schwann cells are the glial cell of the peripheral nervous system. They are dependent on receptor tyrosine kinase-mediated RAS signaling, cell matrix adhesion, and cell-cell contact to proliferate during nerve development and repair. These pathways become deregulated with loss of function of the merlin tumor suppressor encoded by NF2, leading to benign tumors called schwannomas. Patients with NF2-related schwannomatosis (NF2-SWN) develop bilateral vestibular schwannomas that cause hearing loss, tinnitus, and death from brainstem compression if untreated. Severe NF2-SWN causes multiple spinal and peripheral schwannomas and neuropathic pain. Schwannomas require careful monitoring, trial and error use of repurposed anti-cancer …

Serum Protein Signatures For Breast Cancer Detection In Treatment-Naïve African American Women Using Integrated Proteomics And Pattern Analysis, Padma Tadi Uppala, Elmer Rivera, Hyun J. Kwon, Sharon S. Lum

Faculty Publications

Breast cancer is the leading cause of cancer-related mortality in African American (AA) women. In this study we evaluated the serum proteomic profile of AA women with breast cancer using an integrated proteomic framework with multivariate pattern analysis. Using 2D-DIGE, thousands of serum protein spots were detected across 33 gels; 46 spots met criteria for presence, statistical significance, and differential expression. Proteins from the spots were identified by MALDI-TOF/TOF and matched in curated databases, highlighting serum biomarkers including ceruloplasmin, alpha-2-macroglobulin, complement component C3 and C6, alpha-1-antitrypsin, alpha-1B-glycoprotein, alpha-2-HS-glycoprotein and haptoglobin-related protein. LC-MS/MS analysis revealed 163 differentiating peptides after imputing and …

Mechanistic Insight Of Neuropilin-2 Expression During The Progression Of Prostate Cancer, Sanika Bodas

Theses & Dissertations

Advanced prostate cancer represents a particularly aggressive and challenging form of prostate cancer (PCa) that shows resistance to both traditional therapies, such as androgen deprivation therapy, and newer treatment modalities like hormone therapies and immunotherapies. For patients diagnosed with advanced stages of PCa, treatment options are limited, and chemotherapy is often the last line of defense. Unfortunately, chemotherapy can severely diminish the quality of life, particularly in older patients, due to its harsh side effects, including fatigue, immune suppression, and overall physical decline. Despite these challenges, researchers and clinicians remain focused on developing more effective and targeted treatments for patients …

Exploring The Functional Role Of Neprilysin In Pi3k/Akt1 Signaling In Triple-Negative Breast Cancer, Ariadna Daniela Menjivar

Student Scholar Symposium

Our lab is investigating the protein Neprilysin (NEP) and its role in Triple-Negative Breast Cancer (TNBC). Previous bioinformatics data from Dr. Conway’s research indicated that in TNBC cells high in Neprilysin expression (HCC38), the PI3K pathway was the most active signaling pathway. This information suggests that Neprilysin is positively upregulating the PI3K pathway in this cell line. This is interesting given the fact that in the context of TNBC, Neprilysin has been shown to negatively regulate the PI3K/AKT signaling pathway. The PI3K/AKT pathway is the most commonly mutated pathway in breast cancer. AKT is the central mediator protein in this …

Impact Of Zar1l Expression On Drug Response In Breast Cancer Cells, Maryam M. Gerges, Smita Misra

Student Scholar Symposium

Breast cancer (BC) is the most common cancer in women worldwide and the second leading cause of cancer-related deaths among females. BC arises from the uncontrolled proliferation of breast epithelial cells. A crucial gene associated with BC is the Breast Cancer Susceptibility Gene 2 (BRCA2), a tumor suppressor that aids in DNA repair. Proper BRCA2 function helps prevent BC. Our lab studied the cell cycle-dependent expression of BRCA2 revealing that its promoter exhibits bi-directional activity. During cell division, forward activity transcribes BRCA2, while in the resting phase, reverse activity transcribes ZAR2 (Zygote Arrest 1 Like). ZAR2, an RNA-binding protein with …

Pediatric Glioblastoma Molecular Mechanisms, Ariana Trabachino, Joshua Owens

Student Scholar Symposium

Powerpoint presentation

Effects Of Valerobetaine In Fatty-Acid Induced Breast Cancer Cell Proliferation, Carolyn Tran, Maryam Mina, Diyar Fadhil

Student Scholar Symposium

Breast cancer is the second leading cause of cancer deaths among women with 287,500 new cases of invasive breast cancer and 43,250 deaths reported in 2022. In fact, 75% of these deaths aren’t from the initial tumor but due to the spread of breast cancer tumors to other sites, also known as metastases. Breast cancer occurs when breast tissue cells mutate and proliferate uncontrollably, resulting in a lump or mass. In breast cancer, the origin of proliferation, or the primary site, for cancer cells is mostly within the milk ducts. Then, tumor cells can start migrating away from its primary …

Investigating Carnitine-Dependent Mechanisms Of Valerobetaine In Breast Cancer Migration Inhibition, Audrey Birdwell

Student Scholar Symposium

Breast cancer accounts for approximately 297,500 cases annually in the United States, leading to over 43,000 fatalities. These deaths occur due to cancer's ability to bypass the normal cell cycle, proliferating uncontrollably and metastasizing throughout the body. Notably, over 75% of breast cancer-related deaths are attributed to metastases. The hallmark of altered cellular metabolism enables cancer cells to enhance fat metabolism alongside glycolysis, driving increased tumor aggressiveness and higher metastatic rates. Currently, no FDA-approved drugs directly target metastases or prevent migrating cancer cells. Consequently, inhibiting fat metabolism presents a potential strategy to reduce metastases and cancer cell migration; however, existing …

Her2 Amplification In Breast Cancer And Its Treatment Options, Emerald Cole, Zoe Grace Brigance

Student Scholar Symposium

Breast cancer affects approximately 2.3 million women worldwide, causing an estimated 670,000 deaths in 2022. Among its subtypes, 15-20% exhibit overexpression of Human Epidermal Growth Factor Receptor 2 (HER2), a tyrosine kinase receptor that drives tumor aggressiveness. HER2 activates the PI3K and RAS/RAF/MAPK pathways, promoting uncontrolled cell growth, proliferation, and survival. In HER2+ breast cancer, gene amplification leads to excess HER2 protein production, resulting in persistent signaling and unchecked tumor progression. However, this dependency on HER2 presents a key therapeutic opportunity. Trastuzumab, an anti-HER2 monoclonal antibody, inhibits HER2 signaling and enhances immune-mediated cancer cell destruction. When combined with Lapatinib, chemotherapy, …

Evaluating The Sna1 Gene Using Crispr Mediated Knockdown In Ewing Sarcoma Cells, Rosanna Jees, Sonia Cerrillo, Terry Jo Shackleford

Mechanisms of Disease

Ewing sarcoma is a pediatric cancer with limited therapeutic options and poor long-term survival. CRISPR–Cas9–mediated gene editing provides a powerful tool for investigating tumor molecular behavior and identifying potential therapeutic targets. In this study, we worked with CRISPR–Cas9 in Ewing sarcoma ES8 cells to evaluate the roles of the transcription factors SNAI1 and SNAI2, both implicated in epithelial–mesenchymal transition and cancer progression. Using guide RNAs targeting each gene, we assessed proliferation, apoptosis, migration, and long-term survival through Incucyte live-cell imaging and colony-formation assays. Knockout of SNAI1 resulted in decreased cell proliferation and reduced migratory capacity compared with controls, suggesting a …

Effects Of Ptk2 Knockdown On Key Cellular Processes In Es8 Cells, Adrian Cruz, Emiliano Rueda, Dylan Andrews, Terry Jo Shackleford

Mechanisms of Disease

Ewing sarcoma is an aggressive form of pediatric cancer characterized by rapid growth and metastatic potential, with limited treatment options available. PTK2 is a key regulator of many pathways involved in tumor behavior, including integrin-mediated adhesion, survival, and migration. This research lab investigated how CRISPR-Cas9 knockdown of PTK2 can affect cellular processes in ES8 Ewing sarcoma cells. To assess the effectiveness of reducing PTK2 expression, we utilized live-cell imaging, wound-healing assays, measurements of caspase activity, colony formation, and qRT-PCR. Our results showed that incomplete knockdown decreased cell proliferation and colony formation, while also increasing apoptotic activity. Additionally, migratory ability was …

How Cxcr4 Knockdown Affects Tumorigenic Properties In Es8 Cells, Gabriella Galdeano, Damon James, Terry Jo Shackleford

Mechanisms of Disease

C-X-C chemokine receptor type 4 (CXCR4) is a seven-transmembrane G-protein–coupled receptor (GPCR). When activated by its ligand SDF-1 (CXCL12), CXCR4 triggers signaling pathways that promote cell survival, proliferation, angiogenesis, and chemotaxis. Many cancers exploit the CXCR4/SDF-1 axis to support tumor growth and metastasis. Ewing sarcoma (ES8) is an aggressive pediatric bone and soft-tissue cancer, and elevated CXCR4 signaling has been linked to increased migration and metastatic behavior. ES8 cells, a well-established ES8 cell line, provided a model to study how CXCR4contributes to tumor progression. CRISPR-Cas9 genome editing was used to knock down CXCR4 in ES8 cells, delivered through lipid-based transfection. …

Investigating The Role Of Twist1 In Cancer Progression Using Crispr Knockdown, Abby Guerrero, Sofia Perez, Terry J. Shackleford

Mechanisms of Disease

TWIST1 is a transcription factor that plays a critical role in epithelial-mesenchymal transition (EMT), a process that promotes cancer cell migration, invasion, and metastasis. This study investigates the functional role of TWIST1 in cancer progression by using CRISPR/Cas9-mediated knockdown to examine its effects on apoptosis, proliferation, migration, and invasion. TWIST1 was knocked down in cancer cell lines using CRISPR/Cas9 assay. Knockdown efficiency and changes in genes were confirmed by qRT-PCR. Functional assays included caspase assays for apoptosis, MTT assays for proliferation, wound-healing assays for migration, Matrigel invasion assays, and colony formation assays to assess long-term growth and invasive potential. Across …

Itgb1 Knockdown Alters Apoptosis And Proliferation In Ewing Sarcoma Cells, Aditi Kumar, Magdalena Saad, Terry J. Shackleford

Mechanisms of Disease

Integrin beta 1 (ITGB1) is an adhesion receptor that link cells to the extracellular matrix and regulates pathways involved in survival, proliferation, and migration. In order to understand its role in Ewing Sarcoma, we applied CRISPR-Cas9 with two guide RNAs to knock down ITGB1 in ES8 cells. We then assessed changes in cell growth, death, movement, and gene expression using Incucyte live-cell imaging, colony formation assays, wound healing assays, and qRT-PCR. qRT-PCR showed partial ITGB1 reduction, with ITGB1_gRNA2 producing the strongest decrease. ITGB1_gRNA2 also led to a small increase in caspase activity and a 20-30% increase in proliferation at the …

Elucidating The Mechanism Of Neprilysin-Regulated Triple-Negative Breast Cancer Invasion, Kai Lam, Ellie Griner

Student Scholar Symposium

Triple-negative breast cancer (TNBC) is a highly invasive and difficult-to-target form of cancer. It is characterized by a lack of estrogen receptors, progesterone receptors, and human epidermal growth factor 2 receptors, making current targeted therapies ineffective and leaving chemotherapy as the primary treatment option. Previous studies in this lab have linked reduced expression of neprilysin (NEP), a membrane-bound protease that cleaves and inactivates mitogenic peptides, to a highly invasive phenotype in TNBC. Our data indicates that while NEP promotes phosphoinositol 3-kinase (PI3K) signaling, it simultaneously inhibits cellular invasion. Here, we begin to explain a possible mechanism behind the anti-invasive role …

Δ-Valerobetaine As A Novel Inhibitor Of Breast Cancer Cell Migration: Hinders Cellular Migration Of Mcf-7 Cells Through Reducing Atp Concentrations And Fak Activation, Braxton Ivie, Lincoln Brown, Bryson Lovorn

Student Scholar Symposium

δ-valerobetaine as a Novel Inhibitor of Breast Cancer Cell Migration: Hinders Cellular Migration of MCF-7 Cells Through Reducing ATP Concentrations and FAK Activation

Lincoln Brown, Braxton Ivie, Bryson Lovorn, Joshua Owens

Based on female breast cancer diagnoses from 2014-2020, the CDC reports that the 5-year relative survival rate for local and regional breast cancers was 98.9% and 86.3%, respectively, while the survival rate for metastasized cancers was reportedly 32.4%. These discrepancies in survival highlight an increased mortality rate when cancer metastasizes. Interestingly, aggressive tumors have been shown to metabolize fats at higher rates than low-metastatic tumors. Recently, our group has …

Host-Intrinsic Factors Determine Anti-Tumor Efficacy Of Exercise In Pancreatic Ductal Adenocarcinoma, Sumedha Pareek

Dissertations and Theses (Open Access)

Pancreatic Ductal Adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths with a low 5-year relative survival rate of approximately 13.3% for all stages combined. We have previously shown that exercise can improve quality of life and enhance functional capacity among patients with PDAC. Exercise induces a variety of changes in the tumor microenvironment with beneficial effects in several tumor types. However, our understanding of the clinical effects of exercise and the mechanisms that mediate anti-tumor effects are limited in pancreatic cancer.

In this project, using C57BL/6 mice from Taconic Biosciences (Tac) and Jackson Laboratories (Jax), we established a …

A Ralgef Inhibitor Suppresses Lung Cancer Stem Cell Development And Tumorigenesis., Raphael Ngozichi Suarez Jigo

Electronic Theses and Dissertations

The RALGEF family of proteins are direct downstream effectors of the RAS oncoprotein. RALGEFs act as guanine nucleotide exchange factors (GEFs) for downstream RAL proteins, thus tying RAS to the regulation of RAL. Genetic studies have demonstrated RAL proteins to be key drivers of RAS-driven transformation and metastasis. Furthermore, this pathway has been implicated in chemoresistance, exocyst-mediated transport, and the modulation of cancer stem cells. Previous work in our lab reported the activity of a novel pan-RALGEF inhibitor (C4-180) against RAS-driven pancreatic cancer models. Here we show the agent to be active against in vitro and in vivo models of …