Cell and Developmental Biology Commons^™

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 …

Effects Of 2,4-Di-Tert-Butylphenol On Osteogenic And Myogenic Differentiation Of Human Induced Pluripotent Stem Cells, Thanh-Bình Dương

All Theses

Synthetic phenolic antioxidants (SPAs) are a class of compounds used to increase the durability of polymers as well as to increase the shelf-life of food, cosmetics, and other personal care items. Of these SPAs is 2,4-di-tert-butylphenol (2,4-DBP). 2,4-DBP is primarily used in polyethylene crosspolymer pipes, which are now used as a replacement for the traditional copper pipes for household water distribution. However, 2,4-DBP has been found to leach from these pipes into the water, enabling a mode of exposure to humans. 2,4-DBP has been detected in human urine, serum, but more importantly, maternal serum, placenta, and cord blood. …

Unraveling The Genetic Architecture Of Somatic Embryogenesis In Upland Cotton, Adam M. Canal

All Theses

Somatic embryogenesis is the de novo development of asexual embryos because of the plasticity of the plant cell. In tissue culture, the biochemical and genetic mechanisms of dedifferentiated callus tissues can be reprogrammed to transdifferentiate into developed, polarized embryos, which can ultimately regenerate into whole plants. Although this rarely occurs in nature, scientists have exploited this process for decades to regenerate whole plants following gene transformation or for micropropagation. While some species are amenable to in vitro regeneration, upland cotton is particularly recalcitrant, with regenerative potential being confined to only several genotypes. The lack of elite, regenerable genotypes greatly restricts …

Preparation Of Proteins And Peptides From Heat-Stabilized Defatted Rice Bran Via Solid State Fermentation And Investigating For Skin Health, Ali A. Bisly

Graduate Theses and Dissertations

Heat-stabilized defatted rice bran (HDRB) is an abundant and inexpensive agro-industrial by-product of rice milling and rice oil extraction process. Furthermore, HDRB is a potential source of proteins. However, the direct protein extraction has low yield of protein due to the impact of heat stabilization and oil extraction process which made the HDRB proteins bound and interact with other components. This research is based on using solid-state fermentation (SSF), which is a natural and cost-effective approach to facilitate protein extraction from HDRB using Bacillus subtilis (natto) Takahashi as a microorganism.

Response surface methodology (RSM) analysis was used with Box-Behnken design …

Ciliate Endosymbiont Imaging Methodology, Aidan Boving, Roxanne Beinart

Senior Honors Projects

Ciliates, a phylum of diverse microbial eukaryotes, are found in a wide range of environments, including anoxia. Anaerobic ciliates host intracellular methanogenic archaea – a unique type of symbiosis. Despite their importance, anaerobic ciliates and their symbiotic relationships remain understudied. Included in this is the ability to image and quantify the intracellular methanogenic symbionts in a precise, timely and replicable procedure. This project aimed to improve the current fluorescence microscopy methodology used for endosymbiont quantification. The proposed method is intended for use with the Opera Phenix, a high throughput spinning disk confocal microscope which can count large amounts of individual …

Investigating The Role Of Bs21 In Vancomycin-Resistant Staphylococcus Aureus, Daniel Floyd

Senior Honors Projects

Staphylococcus aureus is a Gram-positive pathogenic bacterium commonly known for being the causative organism of staph infections in clinical settings. In previous literature, it has been observed that mutations in certain genes in S. aureus can result in resistance to commonly used antibiotics. Specifically, mutations in the gene rpsU, encoding the ribosomal protein bS21, have been present in strains of S. aureus resistant to the antibiotic vancomycin. The aim of my project is to validate these findings by creating a strain of S. aureus without bS21 and performing an antibiotic assay to determine the level of resistance to vancomycin …

Growth Differentiation Factor 5 Is A Paracrine Regulator Of Sarcopenic Obesity, Landen W. Saling

Graduate Theses and Dissertations

Sarcopenic obesity attributes to skeletal muscle loss more than sarcopenia and obesity alone. Individuals with SO suffer from the comorbidity of excess body fat and concurrent muscle mass loss due to aging. Growth differentiation factors (Gdfs) have never been recognized as playing a role in skeletal muscle maintenance in those with SO. Specifically, Gdf5, has been recognized as playing a part in Bone Morphogenic Protein signaling to activate protein synthesis and deactivate protein degradation via SMAD 1/5/8 and SMAD 4 complex. Using RNA sequencing, Gdf5 was identified as being significantly upregulated in SO mice. Purpose: To determine the cellular role …

Differential Expression Of Cellular And Exosomal Microrna Isolated From Oral Cancer Cells And Their Resistance To Chemotherapy, Brady Petersen

UNLV Theses, Dissertations, Professional Papers, and Capstones

Introduction: MicroRNAs are abundant small non-coding RNA with a variety of known functions, including transcriptional activation and inhibition. Recent evidence has suggested that microRNA expression may influence the responsiveness of some cancers to chemotherapy, including liver and lung cancers. Some evidence has now suggested that specific microRNAs, such as miR-21, miR-155, and miR-375, may influence oral cancer responsiveness to chemotherapy – although much remains to be discovered.

Objective: Based upon the lack of evidence in this area, the primary objective of this study was to evaluate microRNA expression and responsiveness among oral cancers.

Methods: Five commercially available oral cancer cell …

Exploring The Effects Of Varied Land Use On Elemental Concentrations Within Streams, Logan Jennings

Biological and Agricultural Engineering Undergraduate Honors Theses

It is well documented that human activity influences the chemistry of surrounding waters. As such, it is possible that there is a link between land use within a watershed and the chemical composition of the stream. The objectives of this study are to determine if varied land use does affect the concentrations of macronutrients and trace elements present in the streams of Northwest Arkansas, and if so, to determine what extent urban and agricultural development are responsible for these changes. Water samples were collected across 19 streams in the Northwest Arkansas region between January and March of 2022. Water samples …

Modeling Developmental, Molecular, And Behavioral Effects Of An Apolipoprotein-E4 Fragment On The Embryogenesis Of Zebrafish, Madyson Mccarthy

Boise State University Theses and Dissertations

Although the increased risk of developing sporadic Alzheimer’s disease (AD) associated with the inheritance of the apolipoprotein E4 (APOE4) allele is well characterized, the molecular underpinnings of how ApoE4 imparts risk remains unknown. Enhanced proteolysis of the ApoE4 protein with a toxic-gain of function has been suggested and a 17 kDa amino-terminal ApoE4 fragment (nApoE4_1-151) has been identified in post-mortem human AD frontal cortex sections. Recently, we demonstrated in vitro, exogenous treatment of nApoE4_1-151 in BV2 microglial cells leads to uptake, trafficking to the nucleus and increased expression of genes associated with cell toxicity …

Structure-Function Characterization Of Zebrafish Gadd34 And Crep, Alice Thuc Truong, Ciera Wroten, Jessica Woo, Jey Kim, Joshua Tao, Kleo Hong, Twisha Patel

Pacific Undergraduate Research and Creativity Conference (PURCC)

No abstract provided.

Development Of Cloning Vehicles For Expression Of Gc-Maf In Yeast, Tammy Tran, Seohyun Lee, Jane Yu, Wilson Wu

Pacific Undergraduate Research and Creativity Conference (PURCC)

No abstract provided.

Utilizing Pharmacology To Target Transcription Factors Involved With Cancer Onset And Development, Tristan D. Sanders

Mountaineer Undergraduate Research Review

Transcription factors (TFs) are a vital part of every living organism on earth, as they allow for the correct genes to be expressed while much of the genome is never used. They can fall victim to mutations or manipulations that lead to the deregulation of many genes within a cell. If specific genes are over/under-expressed, a cell may become cancerous and begin replicating into a tumor. It has been demonstrated that common TFs associated with cancer can be targeted using small molecule drugs, and a popular target of these drugs is the DNA binding site on the TF along with …

The Central Dogma: Gene Expression, Ayisha Sookdeo

Open Educational Resources

In this lesson plan, students will learn the basic structure and function of DNA and RNA. They will also learn the process of gene expression. Finally, students will learn about the scientific contributor, Ernest Everest Just, and his contributions to the field of Biology.

A Patient-Derived Ipsc Model To Study Glutamate Deficiency By Shank-3 Mutation In Autism Spectrum Disorder, Tiffany Berry, Courtney Caccia

Biology Student Scholarship

Tiffany Berry ’22, Majors: Biology and Psychology

Courtney Caccia ’22, Majors: Biology and Psychology

Faculty Mentor: Dr. Charles Toth, Biology

The use of human stem cell lines derived from persons with Autism Spectrum Disorder (ASD) provides a unique opportunity to model brain growth and potential to regain brain activity for treatment. Our lab has previously used stem cells to derive 3D cardiomyocytes to examine cardiovascular disease as well as kidney organoids and macrophages to study kidney disease. Using techniques our lab has learned using these stem cell models have prepared us to examine cell communication in mutated neurons. We will …

Identification Of Lipid Species: Potential Biomarkers For Early Detection Of Hepatocellular Carcinoma, Kit Yee Leung, Kaylee Freitas

Undergraduate Research Symposium Posters

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. HCC is associated with cirrhosis. Poor survival rate of HCC is due to diagnosis of HCC at late stage.

Jag1 Role In The Extravasation Of Metastasized Tnbc Tumor Cells, Bhavya Vegesna '23

Student Publications & Research

Breast cancer is the second leading cause of cancer death in women. Triple negative breast cancer (TNBC) is an aggressive subclass defined by its lack of hormonal receptors and HER2 amplification. Although TNBC only accounts for 15% of all invasive breast cancers, there are limited therapeutic options for patients with TNBC. Although breast cancer patients have a favorable prognosis if their tumor is detected early, patients with TNBC are prone to earlier recurrence and local/distant metastasis. Consequently, patients with metastatic TNBC have <15% relative 5-year survival rate. The development of metastasis in TNBC is a complex and poorly understood process that includes multiple steps such as genetic and epigenetic alterations, angiogenesis, epithelial-to-mesenchymal transition (EMT), intravasation, and extravasation. Expression of JAGGED-1 (JAG1), a Notch ligand, correlates with metastatic status and poor survival in clinical data. However, the exact mechanism in which JAG1 increases metastasis is unknown. We hypothesize that JAG1 increases metastasis by interacting with endothelial cells. In order to test this idea, we generated JAG1-knockout cells using CRISPR/Cas9 technologies and then modeled the extravasation of these cells compared to JAG1-positive cells. Specifically, we interrogated lung capillary extravasation after intravenous injection of TNBC cells. The lung was chosen due to the propensity of TNBC cells to invade the lung. Preliminary data demonstrates that JAG1 presented in tumor cells acts as a signaler to permit and promote extravasation and metastasis of the cancer cells. For further studies, the long term effects of tumor derived JAG1 will be studied to understand the consequences of JAG1 mediated extravasation on metastatic burden and survival.

Aeromonas Phage Research And The Public Health Impact Of Antibiotics In Aquaculture Workers, Madelyn Merchant

Honors Projects

One of the most common fish diseases in aquaculture is Aeromonas infection. The most common way to treat this infection is through antibiotics. The bacteria in the fish can become antibiotic-resistant and perpetuate the disease. The diseases in fish create a huge financial loss and the industry loses $6 billion per year due to diseases in fish. An alternative to antibiotics is bacteriophage which causes less environmental degradation and is better for human gut flora. In aquaculture there have been examples of aquaculture workers becoming sick from the water in aquaculture ponds as well as from people eating the fish. …

Indispensable Role Of Immunophenotyping In Diagnosing Leukemic Phase Of Blastic Plasmacytoid Dendritic Cell Neoplasm Without Cutaneous Manifestation, Hareem Alam, Nabiha Saeed, Anila Rashid

Department of Pathology and Laboratory Medicine

Blastic plasmacytoid dendritic cell neoplasm usually presents as skin lesions. Diagnostic error occurs when it primarily presents in leukemic phase without skin involvement. Triad of CD4, CD56 and CD123 immunophenotype expression is essential to avoid misdiagnosis of this rare hematological malignancy. Here we describe a patient who presented in overt leukemic phase of BPDCN highlighting diagnostic challenges encountered that resulted in delayed diagnosis and poor outcome