Cell and Developmental Biology Commons^™

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 …

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 …

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 …

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 …

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 …

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

Thinking Matters Student Research 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 …

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 …

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 …

Mitochondrial Network Expansion And Loss During Oligodendrocyte Life And Death, Xhoela Bame

Dartmouth College Ph.D Dissertations

Oligodendrocytes are the myelinating cells of the central nervous system, known for modulating signal transmission, refining neural circuits, and providing metabolic support to axons. Oligodendrocytes are generated throughout life from oligodendrocyte precursor cells (OPCs) and are damaged or lost in demyelinating and neurodegenerative diseases and age-related pathologies. Thus, understanding the cellular checkpoints that occur during the generation and degeneration of oligodendrocytes is crucial for maintaining their population in health and recovering it in disease and aging.

Using high-resolution optical imaging, I have discovered a dynamic redistribution and subcellular partitioning of mitochondria during oligodendrogenesis. Mitochondria transiently expanded towards the differentiating OPC …

Novel Combination Therapies For Estrogen Receptor-Positive Breast Cancer Driven By Rational Molecular Mechanisms, Anneka Lila Johnson

Dartmouth College Ph.D Dissertations

Breast cancer (BC) is the most common non-keratinocyte cancer diagnosed in women in the United States with approximately 300,000 new cases diagnosed each year. Despite a myriad of treatment options, BC remains the second-most deadly cancer. Estrogen receptor-positive (ER+) BC comprises 60-70% of BC diagnoses and is treated with endocrine therapies that limit ER signaling. Despite endocrine therapy options, ~1/3 of patients experience recurrence within 10-20 years of diagnosis. Novel therapeutic strategies are required to limit BC recurrence-related morbidity and mortality.

Radiotherapy is used as an adjuvant treatment for ER+ BC patients prior to the use of endocrine therapy. Radiation …

Unpaired Virtual Histological Staining Of Tissue From Autofluorescence Using Regularized Cycle-Consistent Adversarial Networks, Zhesi Wen

Theses and Dissertations

We present a regularized CycleGAN with a Dense Residual U-Net to virtually stain autofluorescence images of tissue into H&E-like images. Our method outperforms standard architectures, reduces artifacts, and achieves superior FID scores, enabling efficient, label-free, and accurate digital pathology for unpaired datasets using multi-channel fluorescence inputs.

The Role Of Elongin B In Drosophila Melanogaster Muscle Development, Madelyne Dayan

Student Theses and Dissertations

Muscle atrophy is a result of a number of muscle diseases, as well as aging, disuse, and infections. Muscles weakened in these ways exhibit a characteristic decrease in size, strength, and mobility. The similarities between muscle in humans and Drosophila allow for direct comparisons to be made in vertebrates from studying muscle in Drosophila. Differential gene expression has been shown to play an important role in embryonic muscle development in Drosophila melanogaster. A previous study identified Elongin B (EloB) to be involved in somatic muscle morphogenesis in Drosophila, with mutant embryos displaying severe muscle defects, including thin, mis-attached, and missing …

An Analysis Of Cellular And Tissue Function Of Lipin In Drosophila Melanogaster, Judah Christian Scott

Graduate Theses and Dissertations

Regulation of energy expenditure and energy storage is a key characteristic of life. Numerous enzymes play a crucial role in regulating energy metabolism. Lipins are a highly conserved family of proteins that function in both lipid synthesis and gene regulation. In the glycerol-3 phosphate pathway, lipins act as a phosphatidate phosphatase (PAP) producing diacylglycerol. In gene regulation, lipins act as transcriptional co-regulators of metabolic genes. The enzymatic PAP activity occurs in the cytoplasm; however, for lipins to function as gene regulators, they must translocate into the nucleus. Nuclear translocation is facilitated by the nuclear localization signal (NLS) within the protein. …

The Impact Of Maternal Age On The Expression Of Transgenerational Plasticity In Daphnia Pulicaria, Calvin Nguyen

2025 Spring Honors Capstone Projects - Archive

Transgenerational plasticity refers to heritable, non-genetic changes in phenotype that persist across multiple generations and can enhance offspring survivability in variable environments. In Daphnia, increasing maternal age has been associated with maladaptive plasticity. To investigate this relationship, six clones were collected from two Wisconsin lakes and acclimated to laboratory conditions through a common garden rearing process. For each clone, ten replicates were generated and evenly divided between young (clutches 2–4) and old (clutches 5–8) maternal age groups. Offspring were exposed to three dietary treatments for three experimental generations: one fed only green algae, one fed only cyanobacteria (a nutritionally …

Identifying Novel Molecular Targets To Induce Ferroptosis In Drug-Tolerant Cancer Cells Through Computational Modeling, Haris J. Rana

Biological Sciences Undergraduate Honors Theses

Ferroptosis is an iron-dependent, reactive oxygen species (ROS)-driven form of regulated cell death in which the cell membrane is degraded by lipid peroxidation. It is regulated by multiple enzymes, such as glutathione peroxidase 4 (GPX4), which prevents membrane degradation by reducing lipid peroxides and protecting cells from oxidative damage. When inhibitors like RSL3 target GPX4, lipid peroxides build up, and toxic ROS compromises membrane integrity. Traditional anticancer treatments, such as most chemotherapies, aim to eliminate tumor cells by damaging DNA and triggering apoptosis. However, resistance to apoptosis is a “hallmark of cancer,” often resulting in treatment failure. As a distinct …

Inflammatory Response In Ucd200/206 Scleroderma-Prone Chickens To Intradermal Injection Of Silikon 1000, Katee L. Johnson

Animal Science Undergraduate Honors Theses

Intradermal injections of silicone materials have resulted in chronic inflammation and fibrotic reactions in some individuals. The UCD200/206 line of chickens is characterized by spontaneous development of scleroderma/systemic sclerosis (SSc), a fibrotic autoimmune disease. This longitudinal study examined the cellular inflammatory activity initiated by SILIKON 1000 (a silicone product used as a filler in human skin) at the site of intradermal (i.d.) injection and in the peripheral blood in the SSc-prone UCD 200/206 (UCD) chickens and healthy White Leghorn (WL) controls. Specifically, the pulps of growing feathers (GFs) were i.d. injected with SILIKON or endotoxin-free, sterile PBS (8 and 3 …

Differential Regulation Of The Prkacaa Promoter In Zebrafish Melanoma Cell Lines, Maria Fiuk

Theses, Dissertations and Culminating Projects

The Inducible cAMP Early Repressor (ICER) comprises a group of isoforms that function as transcription factors within the cyclic AMP (cAMP) signaling pathway. These isoforms are encoded by the cAMP Response Element Modulator (CREM) gene. The cAMP signaling pathway and its associated transcriptional regulators have been implicated in the development of resistance to BRAF/MEK-targeted therapies in melanoma. Recent findings from our laboratory demonstrated that transgenic ICER expression in a zebrafish melanoma model promotes the formation of aggressive melanomas. Cell lines were established from tumors expressing ICER, as well as from control tumors expressing Green Fluorescent Protein (GFP). To begin characterizing …

Investigating The Effect Of Fasting On Senescent Cells In Nothobranchius Furzeri Fish, Israel A. Akinola

Electronic Theses and Dissertations

Senescent cells (SCs) have been documented to accumulate with age in the organism. Recent studies have shown that reducing the number of SCs in an organism result in tissue rejuvenation and extension of life expectancy. Intermittent fasting is reported to have multiple health benefits and is speculated to reduce the burden of SCs. Nothobranchius furzeri are a new model organism for studying aging and for which there are short- and long-lived strains available. We hypothesize that long- and short-lived strains of N. furzeri will accumulate SCs at different rates; and that fasting will reduce the burden of SCs.

The results …

The Development Of Magmas Inhibition As A Potential Therapeutic Target In Temozolomide Resistant Glioma, Jennifer Duyen Tran

Electronic Theses, Projects, and Dissertations

Glioblastoma (GBM) is a highly aggressive brain tumor that remains a significant challenge in neuro-oncology today. Approximately 90% of GBM patients experience tumor recurrence within one to two years of diagnosis. Therefore, due to its high resistance to conventional therapies, new treatment strategies are urgently needed. The current standard of care for GBM is the chemotherapeutic Temozolomide (TMZ). TMZ is an oral alkylating agent, it functions by delivering a methyl group to purine bases. The development of resistance to TMZ is partially regulated by the DNA repair enzyme O6- methylguanine-DNA methyltransferase (MGMT). Despite the potential shown by MGMT promoter methylation …