Cell and Developmental Biology Commons^™

A Bitter Brew For Cancer: Egcg’S Impact On Ewing Sarcoma Cells, Lizzeth Holguin, Mary-Esther Leblanc, Mariana Reyes, Terry Jo Shackleford

Cell and Molecular Methods

Epigallocatechin Gallate (EGCG), a powerful antioxidant found in green tea, is an abundant treatment to treat Ewing Sarcoma cells, a pediatric cancer affecting the skeletal system. Given EGCG’s known role in other cancer treatments, these tests aim to investigate its effects as a standalone natural compound on Ewing Sarcoma cells. Focusing on the PI3K/AKT pathway, if the PI3K/AKT pathway is inhibited by EGCG, then it will lead to reduced cell survival and proliferation of EW8 cells. Using cell culture techniques, IncuCyte-based IC50 analysis, caspase 3/7, RNA purification, cDNA synthesis, and qRT-PCR, EGCG’s impact was assessed on cell apoptosis and gene …

The Effect Of Epigallocatechin Gallate (Egcg) And Alpha L-Mangostin On Tp53, Bax, And Vim Gene Expression And Apoptosis In Ewing Sarcoma Cells, Victoria Valdez, Terry Jo Shackleford

Cell and Molecular Methods

Ewing Sarcoma (ES) is a malignant pediatric bone tumor driven by chromosomal translocations and fusion oncogenes with limited targeted treatment options. This study investigated the chemopreventive potential of two natural compounds, Epigallocatechin Gallate (EGCG) found in green tea, and Alpha L-Mangostin from mangosteen, on apoptosis and gene expression in ES cells. We hypothesized that EGCG and Alpha L-Mangostin treatment would induce apoptosis and downregulate cancer-promoting genes. To test this, we performed tissue culture, IC50 assays, caspase-based apoptosis detection, RNA purification, cDNA synthesis, and qRT-PCR on ES cell lines treated with a high and low concentration of the two compounds. Our …

Mechanisms That Contribute To Age-Dependent Segregation Errors In Drosophila Oocytes, Zihan Meng

Dartmouth College Ph.D Dissertations

Meiotic chromosome segregation errors in human oocytes are the leading cause of miscarriages and aneuploid pregnancies, and these errors increase dramatically as women age. Using Drosophila oocytes as a model system, this dissertation identifies the NAD⁺-dependent deacetylase Sirt1 as a key regulator of chromosome segregation and meiotic arm cohesion. Loss of Sirt1 activity during meiotic prophase leads to premature loss of arm cohesion and increased segregation errors in Drosophila oocytes. In addition, elevated acetylation of its substrate, histone H4K16, indicates that Sirt1 activity declines in oocytes during aging. Strikingly, dietary administration of the Sirt1 activator SRT1720 preserves Sirt1 deacetylase activity …

Peripheral Neuroimmune Mechanisms Of Chronic Back Pain, Aleyah Esther Goins

Biomedical Sciences ETDs

Chronic back pain (CBP) affects 1 in 10 people worldwide, reducing mobility, productivity, and quality of life. Despite its prevalence, non-addictive treatments remain limited due to an incomplete understanding of chronic pain mechanisms. This dissertation examines peripheral neuroimmune interactions in CBP using a urokinase-type plasminogen activator (uPA)-induced mouse model (uPA-CBP). uPA, a pro-inflammatory serine protease, was injected into the L2/L3 lumbar spinous ligament, inducing prolonged mechanical and cold hypersensitivity. Flow cytometry of dorsal root ganglia (DRG) showed increased CD45+CD11b+ myeloid cells in males and CD45+CD3+CD4+ lymphocytes in females. DRG neurons from male uPA-CBP mice exhibited heightened action potential firing. Pharmacological …

Identification Of Methylation Patterns, Associated Dna Methylating Proteins, And Methyltransferase Inhibitors On The Promoter Regions Of Dax-1, Brandon Tyler Toy

Master's Theses

The DAX-1 gene (Dosage-Sensitive Sex Reversal, Adrenal Hypoplasia Congenita, Critical Region on the X chromosome, gene 1) encodes for an orphan nuclear hormone receptor and its mutation is implicated in multiple diseases including congenital adrenal hypoplasia, adrenal cancer, and breast cancer. Previous research has linked DAX-1 downregulation to tumor initiation in breast tissue, suggesting the gene acts as a tumor suppressor with respect to breast cancer. Additional studies completed by the Tzagarakis-Foster laboratory have shown that methylation of the DAX-1 promoter region is heavily influential in breast cancer development, with release of epigenetic repression resulting in slowing of cellular proliferation …

Dysregulation Of Vitamin D Receptor And Cyp450 Metabolism Enzymes May Explain Oral Cancer Responsiveness, Dustin Hunsaker

UNLV Theses, Dissertations, Professional Papers, and Capstones

Many health benefits are associated with Vitamin D (VitD), although deficiency is associated with poor health outcomes and increased risk for cancer development. For example, many tissue specific enzymes are involved in VitD metabolism, and mutations or deletions within Vitamin D receptor (VDR) genes are known to increase cancer risk by altering their functions or bioavailability, although less is known about these phenomena in oral cancers. Using well characterized, commercially available oral cell lines (OKF4, HGF-1, SCC4, SCC9, SCC15, SCC25, CAL27), mRNA expression of P450 cytochrome VitD metabolic enzymes and receptor genes by qPCR revealed differential results. One oral cancer …

Assessing The Effects Of Streptozotocin-Induced Hyperglycemia On Amyloid Beta Accumulation And Cognitive Behavior In A Mouse Model Of Alzheimer’S Disease-Related Pathology, Andrew Adonay Ortiz

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer’s disease (AD) is an irreversible and devastating neurodegenerative disease characterized by progressive synaptic, dendritic, glial, and neuronal loss, collectively leading to impairments in learning, memory, and deterioration of cognitive and behavioral functions. AD is the most common form of dementia accounting for 60-80% of all cases. AD affects approximately 7 million Americans and is the 6th leading cause of death in the US. Furthermore, by 2050, the US is projected to spend over $1.1 trillion on AD-related treatments. Pathological hallmarks of AD include beta-amyloid (Aβ) plaques, intracellular neurofibrillary tangles (NFTs), and chronic neuroinflammation, which can promote and exacerbate both …

Targeting The Beiging Of Muscle-Associated Adipose Tissue To Promote Muscle Regeneration, Jacob C. Parson

WUSM Theses and Dissertations – All Programs

The expansion of intra-muscular adipose tissue (IMAT) between myofibers and epi-muscular adipose tissue (EMAT) outside of the muscle boundary accompanies numerous pathologies including diabetes, muscular dystrophy, and aging. IMAT and EMAT are anatomically juxtaposed to myofibers. Some evidence supports that IMAT and EMAT impede muscle function. This is potentially due to paracrine factors that are secreted by IMAT/EMAT. Different adipose depots can be classified in numerous ways including where they are located anatomically as well as the factors in which they secrete. Unlike classical white fat, adipose depots classified as brown or beige, noted by the marker uncoupling protein-1 (UCP-1) …

Early Hematopoietic Differentiation Of An Inducible Pluripotent Stem Cell Model Of Infant Lymphoblastic Leukemia, Meagan Vacek, Jacqelyn Nemechek, Irina Pushel, Bradley Thornton, Priyanka Kumar, Jay L. Vivian, John M. Perry

Research Days

This abstract describes our work regarding the differentiation of human inducible pluripotent stem cells into hematopoietic stem and progenitor cells as the groundwork for the development of a genomics driven inducible pluripotent stem cell model of KMT2A rearranged infant acute lymphoblastic leukemia.

Minimal Anti-Cancer Effects Of Mushroom-Derived Compounds Hispidin And Chaga Extract On Ewing Sarcoma Cells, Jordan Cosgrove, Fiona Coulbourne, Iris Reyna, Giselle Serna-Flores, Terry Jo Shackleford

Cell and Molecular Methods

Ewing sarcoma is a rare and aggressive cancer of adolescents and young adults driven by the EWSR1–FLI1 gene fusion. Standard treatments include chemotherapy, surgery, and radiation, though survival rates remain low. Natural compounds such as hispidin, derived from fungi, and Chaga mushroom extract have shown potential anti-cancer effects by disrupting cell cycle progression and promoting apoptosis in other cancer models. In this study, we tested the effects of hispidin and Chaga extract on Ewing sarcoma cells to evaluate their ability to suppress cell growth and identify potential therapeutic benefits.

The Effects Of Panobinostat On Cellular Signaling Pathways And How It Relates To Antitumor Activities In Ewing Sarcoma Cancer Cells, Crystal Valenzuela, Andrew Martini, Hannah Navarro, Mario Flores, Terry Jo Shackleford

Cell and Molecular Methods

Ewing sarcoma is a rare and aggressive cancer that primarily affects the bones and surrounding soft tissues, most commonly in children and young adults. Although the exact etiology remains unclear, a well-documented cause involves a chromosomal translocation resulting in the fusion of the EWSR1 and FLI1 genes. This fusion produces abnormal proteins that disrupt normal gene expression, cell signaling, and RNA processing, contributing to tumorigenesis. Prognosis varies significantly depending on the extent of metastasis, with 5-year survival rates ranging from 82% in localized cases to 39% in metastatic cases. Standard treatments include chemotherapy typically involving vincristine, doxorubicin, etoposide, and cyclophosphamide—surgical …

The Effects Of Hispidin And Eribulin Mesylate On Cell Proliferation Of Ewing Sarcoma Cell Lines, Elena Mares, Angelina Juarrita, Sierra Munoz, Terry Jo Shackleford

Cell and Molecular Methods

Ewing sarcoma is a type of cancer that targets the cells within bones and soft tissue and is most prevalent in younger populations. It is important to look at this specific cancer because there is no cure yet, and the risks increase, even after a patient has completed their treatment. We hypothesize that if we treat Ewing sarcoma cell lines with natural compounds, specifically Hispidin and Eribulin Mesylate, then the cell lines will decrease in cell viability and there will be an increase in apoptosis of the cancerous cell lines. We performed a series of experiments, which included IC50 analysis, …

Neurodevelopmental And Environmental Mechanisms Of Invasion, Proliferation, And Tumor Cell Fate Specification In Glioblastoma, Bianca Lynn Myers

Biomedical Sciences ETDs

Glioblastomas (GBMs) are the most aggressive primary brain tumors, and despite over 50 years of research efforts, the median survival remains at 14 months post-diagnosis. The current standard of care consists of maximal surgical resection radiotherapy with concurrent chemotherapy using temozolomide. However, the highly proliferative and invasive nature of GBM cells renders total resection nearly impossible as tumor cells invade the surrounding healthy tissue. The molecular and environmental drivers of these tumorigenic phenotypes are largely unknown. Here, we demonstrate that the neurodevelopmental transcription factor ASCL1 enhances tumor cell proliferation and invasion while activating the expression of a neural stem cell …

Validating The Ability Of Iag933 To Block The Interaction Of Yap1 And Tead In Ovarian Cancer Cells, Alex Sage

Theses & Dissertations

Ovarian cancer is the most common and deadliest gynecologic malignancy. Approximately 40% of ovarian cancer patients exhibit chemoresistance after receiving initial treatment in the form of neoadjuvant chemotherapy or interval debulking surgery, of which YAP1 (Yes-associated protein 1) has been implicated in enhancing the resistance of ovarian cancer to Cisplatin and Taxol.^1,2. This highlights the need to develop new therapeutic strategies that target the Hippo pathway to overcome resistance to traditional therapies.

YAP1 is a protein that acts as a transcription coregulator, promoting the transcription of genes involved in cellular proliferation and suppressing apoptotic genes. It is a …

Coxiella Burnetii Manipulation Of Membrane Contact Sites In The Intracellular Niche, Margaret F. Sladek

Theses & Dissertations

Coxiella burnetii is a highly infectious and environmentally persistent bacterium that causes the disease Q Fever. Its intracellular home, the Coxiella-Containing Vacuole (CVV), is formed from fusion of host-derived vesicles and is rich in sterols - yet cholesterol accumulation in the CCV is bacteriolytic. Our lab’s goal is to understand how Coxiella manages intracellular cholesterol levels and survives within the host. One way Coxiella may modulate CCV cholesterol is through membrane contact sites (MCS), areas where molecular complexes bridge two organelles and exchange lipids. This thesis explores how Coxiella uses both a mammalian lipid transfer protein and bacterially-encoded effector …

Cholestasis And Fluid Flow Are Biomechanic Regulators Of Cholangiocarcinoma Progression, Andrew Oleksijew

Theses & Dissertations

Cholestasis, altered or absent bile flow, is associated with poor survival in patients with cholangiocarcinoma, an aggressive cancer of the biliary epithelium. Changes in bile flow often result in stricture or obstruction. Experimental cholestasis promoted tumor growth and progression. However, studies are needed that directly assess the mechanical interaction between bile flow, or bile shear stress, and cholangiocarcinoma signaling. We hypothesized that cholestasis and absent bile shear stress activated cancer signaling and increased aggressive cellular behaviors such as proliferation and migration. Fluid shear stress approximating bile flow was applied by orbital culture plate method and compared to identical static culture …

Drivers And Mechanisms Of Golgi Fragmentation As A Modulator Of Disease, Amanda Macke

Theses & Dissertations

The Golgi apparatus plays a pivotal role in post-translational modification, trafficking, and secretion of proteins, ensuring proper cellular function. As a result, its fragmentation has been implicated in multiple pathological conditions, including alcohol-induced liver injury and prostate cancer (PCa). Despite its known impact on cellular homeostasis, the molecular mechanisms governing Golgi fragmentation remain to be clarified. Additionally, we have only just begun to understand the vast consequences of Golgi disorganization on disease progression.

This dissertation investigates the drivers and mechanisms of Golgi fragmentation, with a focus on its role as a modulator of disease. Using both in vitro and in …

Mesoderm-Specific Transcript Has A Role In The Systemic Regulation Of Obesity, Maria J. Orellana Rosales

Thinking Matters Symposium

Mesoderm specific transcript (Mest) expression in white adipose tissue (WAT) is variable in genetically identical mice. Previous studies have shown a connection between Mest high expression and propensity for fat mass expansion. WAT and liver crosstalk has been well documented with hormone-like peptides signaling and regulating important metabolic pathways. The aim of this study is to investigate the correlation between these circulating factors and Mest expression in mice after exposure to a high fat diet (HFD). A group of 120 C57B6/J mice, males and females, were exposed to a HFD (Western Diet, 40 kcal% fat) for 4 weeks (8-12 weeks …

Application Of Bioactive Materials Primary Cilia As A Novel Delivery Vehicle, Ayan K. Barui, Farideh Amirrad, Vansh Goel, Sharareh Ohadi, Rajasekharreddy Pala, Ashraf M. Mohieldin, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are hair-like structured cell organelles functioning as cellular antennae with chemosensory and mechanosensory roles. Dysfunction of cilia results in ciliopathies, including renovascular diseases (polycystic kidneys, hypertension, aneurysm), mental impedances (Alzheimer's disease, Parkinson's disease, dementia), metabolic diseases (obesity, developmental skeleton defects), blindness, and so on. With a diameter of 150 nm, cilia can be cleaved, released and circulated in the body as injury biomarkers. We here assessed the potential use of isolated cilia as a novel delivery vehicle. Cilia were isolated from renal epithelial cells, and a specific-targeting chemotherapeutic was designed on the cilia. The data show a remarkable …

A Search For Transcriptional Cofactors Of Gcm/Repo Involved In Determining Glia Cell Fate In Drosophila Melanogaster, Nivedha Kosalram

Honors Theses

In Drosophila melanogaster, the mechanism influencing the differentiation of glia and neurons is directed by a key transcription factor known as glial cells missing (gcm). gcm is a crucial regulator of cell fate decision, functioning as a binary switch to direct glial fate in gcm- positive cells and neuronal fate in gcm-negative cells (Jones, et.al, 1995; Hosoya, et.al, 1995; and Vincent, et.al, 1996). In addition to directing gliogenesis, gcm and its homolog gcm2 facilitate the determination of macrophages and tendon cells, highlighting that gcm acts with supplementary factors to induce various signaling pathways in different contexts (Jones, 2005; Johnson, et …