Cell and Developmental Biology Commons^™

Glucose Metabolism Of Breast Cancer Sub-Clones That Preferentially Metastasize To The Lungs And Bone, Anna G. Skubiz

Honors Theses

Malignant breast cancers exhibit preferential metastasis to bone and lung (1). While changes in gene expression in lung-specific (LM) and bone-specific metastasis (BoM) lines derived from the MDA-MB-231 breast cancer line have been identified, few metabolic genes are differentially expressed; thus it is unknown if tissue-specific metabolic reprogramming occurs. Two hallmarks of cancer cells are an altered metabolic phenotype characterized by enhanced conversion of glucose to lactate in spite of adequate oxygen availability for complete mitochondrial oxidation of this substrate (referred to as aerobic glycolysis or the Warburg effect) and a greater dependence on glutamine. These changes in primary tumor …

Evaluation Of The Bax-Vdac Interaction And Their Influence On Apoptosis In Drosophila Melanogaster, Frances Marie Gatlin

Honors Theses

Apoptosis, also known as programmed cell death, is a cellular process used for development or for when cells undergo injury or stress. The Bcl2 family of proteins includes both pro-apoptotic and anti-apoptotic proteins that control the intrinsic pathway of apoptosis. Understanding the mechanisms and influence these proteins have on apoptosis is an important area of research focused on in Dr. Jones’s lab. Evidence shows a homology amongst the Bcl2 family of proteins at the BH3 domain. Dr. Jekabsons' lab has found a potential homology amongst VDAC 1-3 and the Bcl2 family at the BH3 domain.

Specifically, our lab is using …

Dimers Of Isatin Derived Spirocyclic Nf-Κb Inhibitor Exhibit Potent Anticancer Activity By Inducing Upr Mediated Apoptosis, Smit Kour

Theses & Dissertations

Activation of NFκB pathway has been implicated in several malignancies and plays a role in many key processes including tumor initiation and progression. The NFκB pathway is activated when TNFα in the tumor microenvironment binds to its receptor, eventually leading to the phosphorylation of the kinase IKKβ. Once active, IKKβ phosphorylates IκBα, a protein that functions to sequester NFκB in the cytosol of resting cells. The phosphorylation of IκBα leads to its degradation in the proteasome and allows NFκB to translocate to the nucleus where it can drive gene transcription. The sulfhydryl groups on solvent-exposed cysteine (Cys) residues of the …

Mitochondrial Metabolism As A Therapeutic Target For Pancreatic Cancer, Simon Shin

Theses & Dissertations

Mitochondria are biosynthetic and bioenergetic hubs that confer cancer cells the metabolic flexibility to survive and grow in harsh tumor microenvironments. Accordingly, mitochondrial metabolism represents a promising target for pancreatic ductal adenocarcinoma (PDAC), which is frequently characterized as desmoplastic and nutrient poor. The findings presented in the first set of studies highlight the importance of mitochondria-dependent metabolic flexibility in PDAC cells upon exposure to acidic conditions. An acidic tumor microenvironment is a common feature of many solid tumors and exerts a profound influence on cancer biology. Similar to previous findings, we demonstrated that low extracellular pH induces epithelial-to-mesenchymal transition (EMT) …

Multi-Generational Effects Of ∆9-Tetrahydrocannabinol Exposure On Gene Expression In Liver Tissue, Kayla Lovitt

Honors Theses

Cannabis is the most commonly used, cultivated, and trafficked illicit drug worldwide. Increased availability and acceptance of cannabis and cannabinoid-containing products provide the necessity for understanding how these substances influence aging. In this study, zebrafish (Danio rerio) were exposed to concentrations of Δ⁹-tetrahydrocannabinol (THC) (0.08, 0.4, 2 µM) during embryonic-larval development, the effects on aging were measured 30 months later and in the offspring of the exposed fish (F1 generation. We observed results indicating a biphasic and hormetic effect. Treatment with the lowest concentration of THC significantly increased egg production, while higher concentrations resulted in impaired …

Cell Proliferation And Viability Inhibition By Resveratrol On Breast Cancer Cell Lines, Kyle Ford Gordon Jr

Honors Theses

Antioxidants are well-known for their various health benefits. They are able to protect cells from being damaged by free radicals that are produced by vital biochemical processes. It has long been known that antioxidants are important in our everyday health, but their potential as disease preventers and potential therapeutic agents is a relatively new field of study. Resveratrol, a natural polyphenol and well-known antioxidant, is found in plants, fruits, and products derived from them, like red wine. Resveratrol has been shown to have various properties, including antiaging, anti-aggregation of platelets, anti-inflammatory, and anticancer activities. Because of their many health benefits, …

Microglia And Fractalkine Involvement In Shaping Multimodal Midbrain Circuitry, Cooper A. Brett

Masters Theses, 2020-current

Microglial cells (MGCs) are highly dynamic and have been implicated in shaping discrete neural maps in several systems. MGCs respond to numerous cues in their microenvironment, including a neuronally-expressed chemokine, CX3CL1 (fractalkine). The present study examines microglial and CX3CL1 patterns with regard to the emerging modular-extramodular framework within the lateral cortex of the inferior colliculus (LCIC). The LCIC is a shell region of the auditory midbrain where discrete compartments receive modality-specific connections, whereby somatosensory inputs terminate within modules and auditory inputs target surrounding extramodular zones. A reliable modular marker, glutamic acid decarboxylase (GAD), enables visualization of emerging modular domains in …

Design Of A 3d Printed Bioreactor For Bone Cancer Research, Brooklyn K. Vanderwolde, Katelyn Hillson

The Journal of Undergraduate Research

Bone cancer is an aggressive disease and has peak occurrence during physiological stimulation of growth and aging. Astronauts who undergo long-term space missions also acquire an increased risk of bone tissue degeneration and cancer. Few in-vitro models currently exist capable of reproducing the complex microenvironment of bone tissue to support multicellular activity in a three-dimensional structure. This limits the ability to understand disease progression and develop suitable treatment strategies. Therefore, developing a bone tissue model and an associated bioreactor is critical to understand the risks associated with cancer progression and improve treatment and preventions related to those risks. The goal …

Using A Novel Cell- Penetrating Peptide Technology To Induce Pluripotency, Laura-Maria Oja

Master of Science in Chemical Sciences Theses

Somatic stem cells have been used as a regenerative medicine tool to treat diseases like leukemia for decades, but they are limited in their ability to self-renew and differentiate. A better alternative, induced pluripotent stem cells (iPSCs), has the ability to generate cells from all three germ layers and avoid tissue rejection as well as bypass the ethical concerns related to embryonic stem cells. In 2006, Takahashi and Yamanaka discovered that only four genes were required to induce pluripotency: Oct4, Sox2, Klf4, and c-Myc (OSKM). Since then, pluripotency has been induced with OSKM most effectively by transfection or transduction. However, …

Neurocognitive Risk Factors And Current Intervention Strategies For Survivors Of Pediatric Acute Lymphoblastic Leukemia, Abigail Taber

Senior Honors Theses

The improved survival rate for pediatric cancer patients is one of the greatest triumphs of recent medicine, but the late effects faced by these survivors have been uncovered through this new population of survivors. Many survivors of pediatric acute lymphoblastic leukemia (ALL) experience cognitive deficits in areas such as attention, memory, processing speed, and academic achievement following cancer treatment. Recent research has pointed to chemotherapeutic agents, host risk factors, and genetic predispositions as perpetrators of these deficits, although other factors are also under investigation. Consequently, the search for appropriate interventions for the amelioration of these deficits has dominated the literature …

Mechanisms Of Statin Effects On Muscle And Neuronal Proteostasis, Daniel Yu

University Scholar Projects

Statins are widely prescribed and used chronically, but we know little about the effects on long-term protein homeostasis during stress and aging. Our aim was to quantify the effect of statins on stress-induced protein damage. We administered atorvastatin in a dose-response curve in Caenorhabditis elegans under naïve control conditions and in conditions of hypertonic and heat stress known to induce muscle damage measurable as countable puncta in a polyglutamine aggregation model of damage. We observed that there is significant polyglutamine aggregation variability among worms at baseline and thus further study requires within experiment baseline controls, per worm. Our results are …

Investigating The Redox Sensitivity Of Mitf Splice Variants, Rachel Berryman

Senior Theses

Within pigment-producing cells known as melanocytes, the transcription factor MITF is intimately involved in regulating genes associated with cell cycle maintenance and melanocyte differentiation. Research, however, has provided conflicting results on the relationship between the expression levels of MITF and melanocyte cell fate. To complicate matters, two splice variants of MITF exist, differing by only 18 base pairs. These variants have been observed at variable levels of expression in melanocyte and melanoma cells, raising the question as to their functional purpose. Building upon previous research by the Leachman/Cassidy lab that identified the redox sensitivity of MITF while additionally establishing a …

The Autoimmune System: The Effect Of Physiological Stressors On Autoantibody Glycosylation And Fidelity Of Autoantibody Profiles, Rahil Kheirkhah

Graduate School of Biomedical Sciences Theses and Dissertations

The presence of thousands of autoantibodies (aABs) in the human sera is typical, and therefore it is possible to identify an aAB profile for each individual. In the first part of this thesis, we will show the cerebrospinal fluid also exhibits an extraordinarily complex immunoglobulin G aAB profile that is composed of thousands of aABs. We show that the pattern of expression of individual aABs in CSF closely mimics that in the blood, indicative of a blood-based origin for CSF aABs. In addition, using longitudinal serum samples obtained over a span of nine years, we show remarkable stability in aAB …

Development Of A Crispr System To Mutate Lpar4 In Chick Retinal Ganglion Cells, Garrett Driscoll

Graduate Theses

Growth cones direct axon pathfinding during neural development by detecting environmental stimuli, known as axon guidance molecules. In vitro studies have shown inhibitory axon guidance molecules to cause growth cones to change morphology to what is called a collapsed growth cone. Lysophosphatidic acid (LPA) has been demonstrated to collapse growth cones in culture, and thus it may act as an inhibitory molecule. However, identification of what LPA receptor is responsible for this physiological response is unknown. To investigate which receptor elicits collapse, we focused on LPA receptor-4 (LPA4) by designing a CRISPR construct to mutate Lpar4 in chick retinal ganglion …

Elucidating The Developmental Defects In Zebrafish Associated With The Cardiac Drug Verapamil, Blake Stephan Justis

Graduate Theses/Dissertations

Birth defects are abnormalities in a developing organism that lead to a malformation in structure or function. Over half of birth defects have no determined cause; however, known causes occur by genetic anomalies, exposure to environmental agents (a.k.a. teratogens), or multifactorial reasons. To explain the unknown causes of birth defects, an area of focus in this study is to identify potential teratogens. Identifying these teratogens, is key to preventing future birth defects. An obvious source of teratogens in pregnant women would be that of pharmaceuticals. Thus, a main goal of this study is to identify drugs that cause birth defects. …

A Novel Uv Resistance In Rad23-Depleted Tetrahymena Thermophila, Emily M. Schmoll

Graduate Theses/Dissertations

Rad23 is a highly conserved cellular scaffold protein which participates in the nucleotide excision repair pathway and ubiquitin proteasome system. It is hypothesized that the contradictory roles of Rad23 within these two systems, acting to enhance stability or facilitate degradation respectively, could be regulated via post-translational modification of the ubiquitin-like domain of the protein. To this end, a Rad23 somatic knockout cell line was established in Tetrahymena thermophila, with the eventual goal of knocking in a mutant Rad23 protein lacking potential for UbL ubiquitylation. In contrast to the UV-sensitive phenotype observed in similar models, Rad23-depleted Tetrahymena cell lines displayed significantly …

Myosin V-Mediated Cargo Traffic Toward The Trans-Golgi Network And Myosin V Implications In Snc1 Exocytosis, Vy Ngoc Khanh Nguyen

Graduate Theses/Dissertations

Retrieval of cargo proteins from the endosome towards the trans-Golgi network (TGN) is a crucial intracellular process for cellular homeostasis. Its dysfunction is associated with pathogenesis of Alzheimer and Parkinson's diseases. Myosin family proteins are cellular motors walking along actin filaments by utilizing the chemical energy from ATP hydrolysis, known to involve in pleiotropic cellular trafficking pathways. However, the question of whether myosins play a role in the trafficking of Snc1 and Vps10 has not been addressed yet. The present study assesses the potential roles of all five yeast myosins in the recycling of two membrane cargo, Snc1 and …

Effects Of Penfluridol On Integrin-Fak Signaling And Tumor Cell Killing In Combination With Oncolytic Hsv In Glioblastoma, Mitra Nair

Dissertations and Theses (Open Access)

Integrins are known to play an important role in activating multiple intracellular pathways, one of which is focal adhesion kinase (FAK). Phosphorylation of FAK can lead to the activation of various downstream signaling pathways that can increase tumor cell growth and proliferation, making it an ideal target for cancer therapeutics. Due to the fact that many FAK inhibitors are limited in their penetration of the blood brain barrier, we investigated the use of Penfluridol, an antipsychotic drug known to attenuate integrin expression at a transcriptional level, in combination with oncolytic herpes simplex I virus (oHSV) in a glioblastoma model. We …

Surface Runoff Alters Cave Microbial Community Structure And Function, Madison Davis, Maria A. Messina, Giuseppe Nicolosi, Salvatore Petralia, Melvin D. Baker, Christiana K. S. Mayne, Chelsea M. Dinon, Christina J. Moss, Bogdan P. Onac, James R. Garey

Molecular Biosciences Faculty Publications

Caves formed by sulfuric acid dissolution have been identified worldwide. These caves can host diverse microbial communities that are responsible for speleogenesis and speleothem formation. It is not well understood how microbial communities change in response to surface water entering caves. Illumina 16S rRNA sequencing and bioinformatic tools were used to determine the impact of surface water on the microbial community diversity and function within a spring pool found deep in the Monte Conca Cave system in Sicily, Italy. Sulfur oxidizers comprised more than 90% of the microbial community during the dry season and were replaced by potential anthropogenic contaminants …

Quantification Of Mammalian Circadian Rhythms In Response To Photopollution With A Focus On Splitting Behavior, Mehdi Khan

University Honors Program Senior Projects

Circadian rhythms are generated by internal biological clocks of organisms and are responsible for the synchronization of an organism’s external and internal environment. The cells responsible for conducting and maintaining the circadian system are known to be coupled in order to maintain a harmonic rhythm. Desynchronization of the master circadian rhythm can cause the presence of two or more rhythms to emerge in a single organism, also known as splitting behavior. Photopollution and artificial light is known to disrupt this synchronization and result in a desynchronized or split rhythm. Many studies have highlighted that photopollution can disrupt the biological clock …