Cell and Developmental Biology Commons^™

Hyper Stable Variants Of Fgf-1-Fgf-2 Dimer, Madison Shields Mcclanahan

Chemistry & Biochemistry Undergraduate Honors Theses

Fibroblast Growth Factors (FGFs), including FGF-1 and FGF-2, are proteins that play a crucial role in cell proliferation, cell differentiation, cell migration, and tissue repair. FGF-1 and FGF-2 are useful in accelerating the healing process in the human body; however, these proteins are naturally thermally unstable, resulting in a relatively low half-life in vivo. 1,8 In efforts to improve the stability of this protein, FGF-1 and FGF-2 proteins are engineered by combining the amino acid sequences of the two proteins to form a heterodimer and obtain novel properties. These two FGF variants are chosen for their specific wound healing capabilities. …

Characterization Of Gangliosides And Fatty Acids In Extracellular Vesicles From Human Milk, Aliya Amin

Food Science (MS) Theses

Extracellular vesicles (EVs) are bioactive components of human milk that may impact functionality to regulate growth, cognitive development, metabolism, and immunity in newborns. The biogenesis of EVs and the mechanism by which EVs elicit biologic effects in vivo have not been characterized entirely. Gangliosides and fatty acids are integral in the formation, release, stability, and functionalities of EVs. Presumably, EV function is related to EV composition and lipids in EVs influence the bioavailability of EV cargo and downstream functions of EVs. The objective of this research was to characterize the fatty acid and ganglioside composition of EVs in human milk. …

Colorectal Cancer Screening In The Latino Population At A Family Medicine Clinic: A Quality Improvement Project, Michael S. Vinson

The Eleanor Mann School of Nursing DNP Capstone Projects

Background: Colorectal cancer (CRC) is a preventable and curable disease that affects all genders, races, and ethnicities, and its impact on society can be reduced with early screening. The Latino population is at greater risk compared to groups or ethnicities due to social determinants and health disparities within the community. Review of Literature: Language barriers, low education levels, persistent social stressors, poor healthcare navigation, and structural barriers make it difficult for this population to be properly screened at appropriate intervals. Purpose: This quality improvement (QI) project was designed to combat reduced screening rates seen in the Latino population. The target …

Translation Control Tunes Drosophila Oogenesis, Elliot T. Martin

Legacy Theses & Dissertations (2009 - 2024)

The decision of a stem cell to either self-renew or differentiate is controlled by specific cellularpathways that can act at the level of transcription, translation, or post-translation. To study the regulation of these pathways in-vivo, I have used the female Drosophila germline as a model system. Each of the steps from germline stem cell (GSC) to egg require changes in cellular pathways. These changes can occur at the level of transcription, post-transciption, translation, or post-translation . Decades of research has elucidated many of the changes to gene that occur during oogenesis, however, many players in this process still remain mysterious. …

Role Of H3k4 Methylation In Myogenesis, Regeneration, And Muscle Disease / Narrative Competence And Cognitive Mapping As A Culturally Sustaining Pedagogy In The Education Of Emergent Bilinguals, Hannah Emily Shippas

Legacy Theses & Dissertations (2009 - 2024)

Muscles are a crucial part of an organism’s wellbeing, as defects in distinct types of muscles can be lethal. Our voluntary muscles, skeletal muscles, go through distinct regeneration phases before reaching maturity. With its own pool of stem cells, muscles have a large potential for regeneration. This potential has led scientists into looking closely at the steps that lead a muscle stem cell into muscle fiber, also known as myogenesis. As a muscle cell moves through myogenesis, genes are led to be turned on/off with different epigenetic mechanisms, one being histone modifications. A methylation modification on the 4th Lysine on …

Headcase Regulates Growth In Response To Nutritional Status Downstream Of Insulin Signaling, Thomas George

Honors Scholar Theses

Cancer cells are notorious for growing in an unrestricted manner without regard for environmental cues. Recently, Li et al. (2019) discovered headcase (hdc) functions by binding to the mTORC1 complex in the mTOR signaling pathway and preventing further signaling. Interestingly, under nutrient restricted (NR) conditions, cells with mutated hdc proteins proliferated more than cells with normal functioning hdc. It is well known that insulin signaling is downregulated under NR conditions, so a potential signaling pathway with insulin, PI3K, PDK1, Akt, PTEN, and hdc was created as a way to explain the link between hdc function and nutritional status. A Drosophila …

Multicopy Suppression Of Ribosomal Protein Deletion Mutants, Jacqualine Cerbone

Senior Honors Projects

To suppress the ribosome assembly defective phenotype of a ribosomal protein uS17- deficient mutant, various ribosomal proteins were used to act as multicopy suppressors. Ribosomal protein uS17 is a highly conserved component of the 30S (small) ribosomal subunit and is important for 30S subunit assembly. Mutants with a deletion of rpsQ (the gene encoding uS17) are viable but have a severe 30S subunit assembly defect and a temperature-sensitive (ts) phenotype. While fully assembled 30S subunits do form, incomplete ("20S") particles lacking several proteins accumulate. We hypothesized that increasing the intracellular concentration of one or more of the proteins missing from …

The Contribution Of Alternative Splicing And Post-Transcriptional Mechanisms Toward The Global Control Of Sumo1/2/3 Sumoylation, Myriah Lorraine Acuna

Open Access Theses & Dissertations

Evolutionary pressures have caused eukaryotic cells to develop various response mechanisms to changing environments, particularly stress adaptations that have been inherited over time. SUMOylation, the post-translational conjugation of the Small Ubiquitin-like Modifiers to a lysine residue on target proteins, is well-documented to regulate essential processes within the cell, including nucleocytoplasmic transport, transcription, apoptosis, protein stability, and progression through the cell cycle (1). SUMO protein levels have been reported to increase upon diverse stress states, including viral infection (2), cardiovascular ischemic events (3), temperature shock (4), and cancer (5). However, very little is known about how SUMOylation is regulated within the …

Investigating The Impact Of Hypoxia On Reactive Oxygen Species Generation Within Murine Breast Cancer Cells, Jared Mcpeake

Biomedical Engineering Undergraduate Honors Theses

When cancer metastasizes from a primary tumor site to secondary site through the bloodstream or lymph, the cancer becomes more difficult to treat. For this reason, it is vital to study what indicates the metastatic potential of a tumor. Current research has shown that cell lines with high metastatic potential display increased levels of metabolic adaptability over their nonmetastatic counterparts after undergoing hypoxic conditions. One method of assessing this adaptability is to measure the concentration of reactive oxygen species (ROS) produced by the cells while undergoing oxidative stress. In highly adaptable metastatic cells, an increase of ROS buildup within the …

Structural Formation And Functionality Of The Spoiie Protein In Clostridium Difficile, Rachel Siebenmorgen

Biological Sciences Undergraduate Honors Theses

My research efforts were directed toward the structure and functionality of a protein, designated SpoIIE [11], which previously has been shown to regulate C. difficile peptide utilization in addition to sporulation and toxin release. The SpoIIE protein is found in all spore-forming gram-positive bacteria and is a crucial component in activation of transcription factors and septum formation thus affecting the regulation and timing of spore development [11,12]. A truncated form of the SpoIIE protein named SpoIIE∆TM was used in an effort to determine the structure of an important but uncharacterized linker domain of the protein. If the structure and specific …

Investigating The Potential Role For The Nervous System In Controlling Regeneration In Nematostella Vectensis, Kristen Malir

Biological Sciences Undergraduate Honors Theses

Nematostella vectensis is a marine sea animal that has become a model for developmental and evolutionary research. Included in the phylum Cnidaria, N. vectensis’ was chosen as the model for this research. Not only can this animal go through asexual and sexual reproduction, but it also has the ability to regenerate. Although much research has been put forth in an effort to understand regeneration better, much is still unknown. The underlying mechanisms of regeneration in Cnidaria are illusive; however, studies within vertebrates have shown the substantial role of the nervous system. The objective of this experiment is to test if …

A Mechanistic Study On The Immunological Effects Of A Novel Anti-Schistosomal Compound, Caleb M. Sandall, Paul H. Davis

Theses/Capstones/Creative Projects

Schistosomiasis is a condition caused by a parasitic worm infection that is one of the primary neglected tropical diseases. It infects approximately 250 million people every year, and it causes the second largest economic impact from any parasitic disease. There exists a treatment for Schistosomiasis; however, it is ineffective against the juvenile stages of the worm. A novel drug has been developed that has been illustrated to have efficacy against all stages of worm infection. However, before this drug can be utilized, its method of action must be determined. Preliminary single cell transcriptomic data from our lab suggests that our …

Investigation Of Microbe And Host Tissue Interactions Contributing To The Pathogenesis Of Colorectal Cancer, Ryan Chapman, Dhundy Bastola

Theses/Capstones/Creative Projects

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. The pathogenesis of this disease can fall under broad categories; however, the specific precursory mechanism of CRC pathogenesis is still unknown. Dysregulations of the gut microbiome have been identified in the CRC tissue environment. Additionally, CRC tissue gene expression has been observed to differ from that of healthy tissue. Despite these noticeable changes, few studies have directly compared the microorganism composition to the gene expression of CRC tissue. Doing so may identify whether the differentially abundant microorganisms influence the changes in gene expression. The goal of this …

Role Of Galactose, Thiazolidinediones, And Neet Proteins In Mitochondrial Physiology And Therapeutic Development., Robert Anthony Skolik

Electronic Theses and Dissertations

This dissertation explores the relationship between mitochondrial physiology and development of therapeutics. Mitochondrial dysfunction is associated with both acute and chronic forms of pathophysiology. This work aims to address development efforts at the cell culture and drug-target levels with respect to mitochondria. At the cell culture level, I characterize an approach that has been shown to improve the physiological dependency on mitochondria in tumor-derived cells. I demonstrate that prolonged replacement of glucose with galactose in culture medium induces a global metabolic shift in hepatocellular carcinoma (HepG2) cells to closer reflect a primary hepatocyte phenotype (Chapter 2). I characterize this shift …

Cannabinoids And Retinal Fibrotic Disorders., Lucy June Sloan

Electronic Theses and Dissertations

Retinal fibrosis is detrimental to vision. Retinal pigment epithelial (RPE) cells contribute to several retinal fibrotic diseases. Upon exposure to TGF-β, a key fibrotic cytokine, RPE cells trans-differentiate to myofibroblasts marked by the integration of α-SMA fibers into F-actin stress fibers, which confer strong contractility. Myofibroblasts produce and contract the collagen-rich fibrotic scar and disrupt retinal architecture. In this study, we investigated the in vitro effects of the putative endocannabinoid compound N-oleoyl dopamine (OLDA) on TGF-β2 induced porcine RPE cell contraction and α-SMA expression. Using an in vitro collagen matrix contraction assay, we found that OLDA inhibited TGF-β2 induced contraction …

Novel Regulators Of Cellular Secretion Alter The Tumor Microenvironment To Drive Metastasis, Rakhee Bajaj

Dissertations and Theses (Open Access)

Lung cancer is a highly aggressive disease responsible for ~25% of all cancer-related deaths, due in part to its proclivity to metastasize. Treating metastasis holds potential for improving patient survival but requires a deeper investigation into the underlying mechanisms. Some of these processes that can regulate metastasis are: (1) Oncogenic targets of epithelial micro-RNAs (miRNAs) are epigenetically de-repressed upon loss of the miRNAs during epithelial-to-mesenchymal transition (EMT) and in cancer. EMT confers plasticity and fitness to cancer cells promoting their survival through the metastatic cascade. This cascade and EMT are initiated by loss of the miRNA200 family (miR-200) and the …

The Effects Of Metronomic And Maximum-Tolerated Dose Chemotherapy In Colorectal Cancer Angiogenesis: A Combined Approach Using Endoscopic Diffuse Reflectance Spectroscopy And Mrna Expression, Ariel Isaac Mundo Ortiz

Graduate Theses and Dissertations

Colorectal cancer (CRC) continues to be one of the most incident and deadliest types of cancer worldwide. Chemotherapy has proven effective to reduce tumor burden for CRC patients, but there are several disadvantages associated with the use of mainstay maximtolerated dose (MTD) chemotherapeutic strategies. Metronomic chemotherapy (MET) has been developed as an alternative that addresses the shortcomings of maximum-tolerated dose chemotherapy but so far its effectiveness as a neoadjuvant strategy for CRC has not been explored.

This dissertation uses a combined optics and molecular biology approach (using diffuse reflectance spectroscopy and mRNA expression) to study the changes in angiogenesis and …

Characterization Of The Influence Of A Small Molecule Inhibitor On Ras-Related Proteins Interactions, Emilio Duverna

Graduate Theses and Dissertations

The Ras superfamily of small G proteins are involved in cell-signaling processes that, if not regulated, may lead to cell multiplication, apoptosis inhibition, and tumorigenesis. They function as molecular switches, which through GTP/GDP exchange cycle, switch on or off cellular activities. Overexpression and/or hyperactivity of these proteins have been linked to many diseases including various cancers. CDC42, a member of the Rho subfamily of the Ras superfamily of small G proteins, participates in the regulation of many cellular processes including cell adhesion, mitosis, and cytoskeletal rearrangements. CDC42 binds to and activates many effector proteins including CDC42-activated kinase (ACK). Abnormal activities …

Generation Of Baiap3 Expression Construct For Subcellular Localization And Phenotypic Rescue, Ireland Ann Little

Honors Theses

Mast cells secrete a variety of biological mediators crucial for innate and adaptive immunity. One such mediator is Tumor Necrosis Factor (TNF). TNF released from mast cells and other immune cells has been shown to elicit complex signaling pathways in target cells, resulting in the production of pro-inflammatory cytokines and/or immune cell recruitment. At the molecular level, TNF secretion/exocytosis is mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) and other regulatory proteins that work together to promote the fusion between secretory granules and the plasma membrane. One regulatory protein, Munc13-4, which facilitates the priming of secretory granules, was recently …

Development Of A Long-Read Sequencing Protocol To Assess The Precision And Efficacy Of Gene Editing For Duchenne Muscular Dystrophy, Landon Andrew Burcham

Graduate Theses and Dissertations

This work establishes a method for assessing on-target precision due to CRISPR-Cas9 gene editing, especially within the context of exon skipping therapy for Duchenne Muscular Dystrophy. The proposed method utilizes an Oxford nanopore long-read sequencing approach to sequence amplified regions of DNA that have been edited using CRISPR-Cas9. NIH3T3 and C2C12 cell lines were treated with a dual-guide CRISPR-Cas9 system, that targets and deletes exon 23 from the DMD gene in mouse samples. Deletion PCR revealed deletion of exon 23 in both DNA and cDNA samples. Additionally, sequencing using Oxford Nanopore revealed targeted exon 23 deletion as the most prevalent …

Functional Role Of Ppal And Potential For Moss In Industrial Applications., Susana Perez Martinez

Electronic Theses and Dissertations

This dissertation is an examination and characterization of the functional roles of PPAL. PROTEIN PRENYLTRANSFERASE ALPHA SUBUNIT-LIKE (PPAL) is a recently discovered gene. PPAL homologs are present in all plants and many animals, where its function is largely unknown. It is possible that PPAL could participate in prenylation processes since it shares similarity to the α subunits of known prenylation enzymes. Prenylation is a post-translational modification of proteins that involves the addition of a lipid moiety to proteins to facilitate membrane targeting and association and promote protein-protein interactions. Prenylation has important roles in plant growth and development, including …

The Roles Of Pon2 In Mitochondrial Physiology, Lung Tumor Cell Proliferation, And Lung Tumorigenesis., Aaron Whitt

Electronic Theses and Dissertations

Paraoxonase 2 (PON2) is an intracellular, multifunctional enzyme with near-ubiquitous tissue distribution. Within cells, PON2 is localized to mitochondria and endoplasmic reticulum (ER), where it mitigates the formation of reactive oxygen species (ROS). PON2’s chief enzymatic function is its lactonase activity, through which it catalyzes the hydrolysis of a bacterial quorum-sensing molecule, N-(3-oxododecanoyl)-l-homoserine lactone (C12), effectively disrupting bacterial intercellular communication and protecting against infection. C12 is produced by the opportunistic pathogen Pseudomonas aeruginosa and has been shown to disrupt various aspects of eukaryotic host cell physiology and evoke apoptotic cell death through the activity of PON2. Additionally, PON2 has garnered …

Regulation Of C-C Chemokine Receptor 7 (Ccr7) Ligand-Mediated Internalization And Chemotaxis By G Protein-Coupled Receptor Kinase Family 4 (Grk-4, 5, 6) In Human Pediatric T-Cell Acute Lymphoblastic Leukemia (T-All), Eduardo Elias Chaib

Open Access Theses & Dissertations

Background and Significance: The Hispanic population is disproportionally affected by T-ALL (T-cell acute lymphoblastic leukemia) when compared to other races in the US. C-C Chemokine Receptor 7 (CCR7) in T-ALL is used during disease progression, and may lead to migration of cancerous cells into the Central Nervous System (CNS) of patients. Goals and Objectives: This project aims to find relevant rates and risk factors for T-ALL for the Hispanic population in the US/Mexico border region. The other aim is to assess the effect of the G protein-coupled Receptor Kinase 4 (GRK-4) family proteins on migration and receptor internalization through CCR7 …

When Problems Become Solutions: Harnessing The Osteogenic Capacity Of Disease-Causing Stem Cells To Repair Bone Fractures, Mehreen Pasha

Honors Scholar Theses

While we often perceive disease as negative, there is potential to engineer seemingly negative biological phenomena into therapeutics to treat a variety of human illnesses. Fibrodysplasia ossificans progressiva (FOP) is a genetic disorder involving uncontrolled, widespread, extraskeletal bone growth, or heterotopic ossification (HO). In FOP patients, stem cells called fibro/adipogenic progenitors (FAPs) follow an abnormal, osteogenic pathway. In the present study, we investigate whether we can adapt these Acvr1 mutant FAPs, which are exceptional at producing bone, to repair bone fractures in otherwise normal patients. The primary aims of this study are (1) to devise and optimize a novel method …

Exploiting Chemogenetic And Genetic Interactions In Human Cells As An Avenue For New Therapeutic Opportunities, Medina Colic

Dissertations and Theses (Open Access)

The advent of CRISPR technology and its adaptation to the mammalian genome made whole-genome knockout screens possible directly in human cells. Gene knockout answers how essential that gene is for cell fitness and proliferation. Genes showing moderate to severe fitness defects are called essential genes and provide insights into disease-specific candidate therapeutic targets. Additionally, CRISPR offers other applications for genome editing. Two applications this dissertation is based on are 1) combination of gene knockout and drug treatment, which enables the identification of chemogenetic interactions, or gene mutations that enhance or suppress the activity of a drug, and 2) combinatorial editing, …

An Investigation Of Epigenetic Mechanisms Driving The Biology Of Head And Neck Squamous Cell Carcinoma, Scot Carson Callahan

Dissertations and Theses (Open Access)

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and is associated with significant morbidity and mortality. To date, the majority of work in the field has focused on genomic alterations such as mutations and copy number alterations. However, the clinical success of targeted therapies that exploit known genomic alterations, such as EGFR mutations, has remained mixed. Over the past decade, the importance of epigenetic regulators has come to the forefront, with the realization that many of these genes are mutated in cancer. Despite this realization, the role of epigenetics in regulating tumorigenesis, progression and …

Modulation Of Kras Structure And Dynamics By Kras Ubiquitination And Membrane Depolarization, Vinay Nair

Dissertations and Theses (Open Access)

KRAS, a 21 kDa small GTPase protein, functions as a molecular switch playing a key role in regulating cell proliferation. Dysregulation of KRAS signaling by oncogenic mutations leads to uncontrolled cell proliferation, a hallmark of cancer cells. Attempts to therapeutically target oncogenic KRAS have led to limited success resulting in a need to identify new mechanisms to targeting KRAS. The interaction of KRAS with its regulators, effectors, and the membrane present one such avenue. In this study, we investigated how post-translational covalent and environmental modifications could modulate these interactions of KRAS. Using computational molecular dynamics simulations, nuclear magnetic resonance spectroscopy …

Integration Of Biomedical Imaging And Translational Approaches For Management Of Head And Neck Cancer, Abdallah Mohamed, Abdallah Mohamed

Dissertations and Theses (Open Access)

The aim of the clinical component of this work was to determine whether the currently available clinical imaging tools can be integrated with radiotherapy (RT) platforms for monitoring and adaptation of radiation dose, prediction of tumor response and disease outcomes, and characterization of patterns of failure and normal tissue toxicity in head and neck cancer (HNC) patients with potentially curable tumors. In Aim 1, we showed that the currently available clinical imaging modalities can be successfully used to adapt RT dose based-on dynamic tumor response, predict oncologic disease outcomes, characterize RT-induced toxicity, and identify the patterns of disease failure. We …

Development And Characterization Of B7-H3-Targeted Radioimmunotherapies For The Treatment Of Solid Tumors, Sarah Glazer

Dissertations and Theses (Open Access)

Radioimmunotherapy involves the selective targeting of therapeutic radionuclides to cancer-associated cell surface antigens using monoclonal antibodies. Radioimmunotherapy has been successful in treating hematologic cancers, such as non-Hodgkin’s Lymphoma. However, treatment of solid tumors by radioimmunotherapy remains a challenge, driven in part by a lack of high affinity antibodies against highly tumor-selective surface antigens. Herein, we characterize novel anti-B7-H3 immuno-conjugates for PET imaging and RIT of solid tumors in preclinical models.

Human B7-H3 (CD276) protein is highly expressed on solid tumor cell surfaces and endovascular surfaces in a wide variety of cancers (colon, breast, pancreatic, prostate, head and neck, glioblastoma, ovarian, …

Plant Homeodomain Finger Protein 20 (Phf20) And Its Homolog Phf20 Like 1 (Phf20l1) Define Two Distinct Non-Specific Lethal (Nsl) Complexes, Hieu Van, Hieu T. Van

Dissertations and Theses (Open Access)

Plant Homeodomain Finger Protein 20 (PHF20) and its homolog PHF20 Like 1 (PHF20L1) are known subunits of the Non-Specific Lethal (NSL) complex, which acetylates lysine residues on histone H4 and regulates gene expression. The current model assumes that PHF20 and PHF20L1 are present together in the NSL complex, although it has never been tested. Performing extensive biochemical analysis, we observed that PHF20 and PHF20L1 were exclusively and independently associated with the NSL complex. Our protein domain analysis showed that the C-termini of PHF20 and PHF20L1 are crucial for their interactions with the respective complexes. Furthermore, enrichment sites of PHF20 and …