Cell and Developmental Biology Commons^™

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 …

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 …

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 …

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. …

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 …

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 …