Cell Biology Commons^™

The Effects Of Vitamin K On Neuronal Ferroptosis, Chelsey P. Eighmey

Electronic Theses & Dissertations (2024 - present)

Dementia is a crippling illness affecting millions worldwide causing significant public health burdens with long-term care. The lack of treatment options results in many years of suffering for affected individuals and their loved ones who often become primary caretakers. Decades of study have focused on treating dementia with little-to-no success, so an emphasis is needed on attempting to prevent disease progression altogether. This research explored vitamin K as a potential strategy for prevention of dementia onset or progression through the mechanism of suppressing ferroptosis. Ferroptosis is a type of cell death suggested to contribute to the hallmark traits of Alzheimer’s …

Multifunctional And Adaptive: Tracking How Fibroblasts Respond To Tissue Injury And Facilitate Tissue Remodeling, Joey R. Tavarez

Electronic Theses & Dissertations (2024 - present)

Fibrosis is characterized by an accumulation of proteins in the extracellular matrix (ECM) that results in altered tissue architecture and reduced organ function. In the salivary glands, fibrosis leads to loss of saliva, dysbiosis of the oral microbiome, an increase in oral infections, difficulty in digestion of food and an overall reduction in the quality of life. Understanding the progression of fibrosis and how it affects human health is a crucial step for designing effective therapeutics. Understanding fibroblast function is integral to advancing the field due to the many roles they play in maintaining the ECM. To perform preliminary analysis, …

Elucidating The Effects Of Environmental And Physiological Conditions On Stem Cell Regulation In Vivo, Nimmy John

Electronic Theses & Dissertations (2024 - present)

The Notch signaling pathway is a highly conserved intercellular signaling pathway that any dysregulation can lead to a variety of human diseases. These diseases are further exacerbated by various environmental, pathological and genetic conditions. Previous studies have shown that these conditions have been known to affect the Notch transcriptional response. However, the molecular mechanisms by which such conditions influence Notch signaling remained largely unknown. Moreover, most Notch studies have relied on in vitro systems and indirect reporters, which can miss the dynamic and contextual nature of Notch signaling. Here, we systematically analyzed the effects of these conditions with single molecule …

Unveiling The Cell Composition Of The Olfactory Migratory Mass: Perspectives On Terminal Nerve Formation, Olfactory Development, And Migration Of The Gnrh-1 Neurons, Enrico Amato Jr.

Electronic Theses & Dissertations (2024 - present)

Puberty is a postnatal developmental process required to initiate key sexual maturation events that are necessary for the propagation of species. Signals to initiate these events first begin with the Gonadotropin releasing hormone-1 (GnRH-1) neurons within the hypothalamus. The hormone GnRH-1 released by these neurons is crucial for puberty, fertility and reproductive processes by establishing the hypothalamic-pituitary-gonadal (HPG) axis, regulating release of sex hormones (Progesterone, Estrogen, Testosterone). Conditions related to inability of the GnRH-1 neurons to correctly release GnRH-1 can lead to aberrant or delayed puberty, a condition known as hypogonadotropic hypogonadism (HH). Interestingly, some patients with the hormonal disorder …

Developing Cellular Systems To Elucidate Rna Structural Dynamics Of Cag Expansion Transcripts In Spinocerebellar Ataxias, Victoria Demeo

Electronic Theses & Dissertations (2024 - present)

Spinocerebellar ataxias (SCAs) are a diverse group of over 40 genetically heterogeneous neurodegenerative disorders, many of which are caused by a trinucleotide CAG repeat expansion in the coding region of specific genes. These expansions lead to the production of polyglutamine (polyQ) tracts that interfere with normal protein function, triggering cellular dysfunction and contributing to disease pathogenesis. The most well-known of these SCAs, such as SCA1, SCA2, and SCA3, exhibit progressive neurodegeneration, yet the precise mechanisms through which these mutations cause disease remain poorly understood.

A significant challenge in studying CAG repeat expansion disorders lies in the complexity of the disease …

Understanding SjöGren's Syndrome As A Systemic Autoimmune Disorder, Gaietchyne Chery

Legacy Theses & Dissertations (2009 - 2024)

Sjögren’s syndrome is an autoimmune condition characterized by a dysfunction in the lachrymal and salivary glands which results in dry eyes and dry mouth. Since its first description in 1892, the disease is one of the most common autoimmune diseases after lupus erythematosus and rheumatoid arthritis in the United States. Despite its high prevalence in the general population, Sjögren’s syndrome remains hard to diagnose due to the wide range of symptoms associated with the disease that is also shared by other conditions. Furthermore, the mechanisms behind the pathogenesis are not properly understood even though multiple factors have been proposed to …

Parallel Networks That Govern The Transcriptional Response To Stress, Serene Anne Durham

Legacy Theses & Dissertations (2009 - 2024)

The transcription factor, p53, plays a pivotal role in the oversight of many stimulus-dependent pathways. Its ability to respond to a wide variety of cellular stress stimuli by activating a broad range of target genes has led it to be characterized as a stress-dependent transcription factor. Our research focuses on deconvoluting the varied transcriptional response to distinct stress signals in an attempt to define the regulatory strategies leading to gene activation after cell stress. We have found that distinct stress response networks, some of which are p53-independent, are converging at activation of a common set of target genes. Our data …

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 …

Salivary Gland Stromal Heterogeneity And Epithelial Controls, Nicholas L. Moskwa

Legacy Theses & Dissertations (2009 - 2024)

Organogenesis is the process organs go through where cellular communications coordinate all a developing organ needs. What organs need are more cells, in the right place, doing the right job. In the salivary gland, we know that stromal cells are important for organogenesis and that they coordinate the epithelium’s form and functions. However, specific stromal contributions have focused on epithelial quantity and placement. There is less information about how the stroma directs the epithelium towards certain functions. Here we used organoids as a model for understanding what stromal signaling directs epithelial cell fate. We found that stromal cell state is …

Genetic Regulation Within Cellular Stress Response Pathways, Jhos M. Dufflart

Legacy Theses & Dissertations (2009 - 2024)

Cellular stress is something that a cell deals with on a regular basis. Fortunately, there are several different mechanisms that are set in place in order to deal with them. Depending on the stress present in the cell there will be different stress response pathways that are activated in order to mitigate the stress or initiate cellular death mechanisms. Transcription factors (TFs) are key components within these pathways, and this will be the focus of this thesis. TFs within mammalian stress response pathways are tasked with the essential regulation of multiple genes within these pathways and are oftentimes linked with …

Exploring The Roles Of Stress, Codon Usage, And Rna Modifications In Myotonic Dystrophy Type 1, Afrooz Golestanian

Legacy Theses & Dissertations (2009 - 2024)

Myotonic dystrophy (DM), the most common form of muscular dystrophy, is a neuromuscular disease caused by microsatellite repeat expansions. It can represent a multi-systemic autosomal dominant disease with DM1 and DM2 subtypes. A cytosine-thymine-guanine (CTG) triplet repeat in the 3’ untranslated region (3’UTR) of myotonic dystrophy protein kinase (DMPK) gene causes DM1 disease, which leads to the production of a longer, abnormal and toxic mRNA. The toxic DMPK mRNA sequester the splicing proteins such as Muscle blind-like (MBNL) and rbFOX which leads to gene expression alteration. Repeat associated non-AUG (RAN) translation also occurs in DM1. Mitochondrial dysregulation has also been …

Study Of Primary Cilium Structure And Intraflagellar Transport, Shufeng Sun

Legacy Theses & Dissertations (2009 - 2024)

Primary cilia are hair-like protrusions that stem from the basal bodies in the cytoplasm and extend into the extracellular space to sense signals. Intraflagellar transport (IFT) functions to transport cargo molecules into and out of the ciliary compartment to assemble, maintain, and disassemble the cilia. Accurate knowledge of the three-dimensional (3D) structure of primary cilia and precise details of the IFT profile is the foundation for understanding the sensory functions of primary cilia. This work covers three aspects of primary cilia. Firstly, we obtained and analyzed the overall 3D architecture of the complete primary cilia axoneme region using serial section …

Tgfbeta1 And Stat3 As Regulators Of The Ha Synthesis And Signaling Pathway, Brenda Goretty Trevizo

Legacy Theses & Dissertations (2009 - 2024)

The studies described here explored the role of Transforming Growth Factor Beta-1 (TGFβ1) and Signal Transducer and Activator of Transcription 3 (STAT3) as potential regulators of the Hyaluronic Acid (HA) synthesis and signaling pathway in human mammary cells. Our results support previous findings in which TGFβ1, a well characterized driver of the epithelial-mesenchymal transition (EMT) has been shown to regulate HA synthesis and signaling. Interrogation of The Cancer Genome Atlas (TCGA) indicated HAS2 expression positively correlated with TGFβ1 mRNA expression in breast cancer patients and in breast cancer cell lines. RT-qPCR experiments were used to measure the expression of the …

Sensing Ribonuclease H Activity With Dna Nanoswitches, Ruju Trivedi

Biological Sciences

Ribonuclease H (RNase H) is a damage-repair protein and ribonuclease that specifically catalyzes the hydrolysis of RNA in an RNA/DNA duplex and breaks down RNA/DNA junctions. It plays an important role in a variety of biological processes including DNA replication, DNA repair, and transcription. It is also pivotal in anti-HIV drug development and the analysis of cellular processes and has been shown to be a potential therapeutic target for various neoplastic diseases. This thesis discusses a unique assay based on DNA nanoswitches to detect RNase H levels and activity. The assay is based on conformational changes of DNA nanoswitches in …

The Stromal Response In Salivary Gland Injury, Kevin O'Keefe

Legacy Theses & Dissertations (2009 - 2024)

Abstract

Tfap2e/Ap-2e Is A Transcriptional Regulator Controlling Neuronal Identity And Circuitry Formation In The Mouse Accessory Olfactory System, Jennifer M. Lin

Legacy Theses & Dissertations (2009 - 2024)

Developmental progression is driven by specific spatiotemporal gene expression, which give rise to consistently patterned organisms despite environmental and genetic variation. The specific activation of robust gene regulatory networks that define tissue structure and individual cellular identity are necessary for tissue and cell specific programs to be activated. Cellular specification is guided by the interplay of intrinsic and extrinsic signals at specific developmental timepoints. The molecular mechanisms underlying the acquisition and maintenance of individual cellular identity remains a fundamental question across biological systems. Understanding the regulatory networks controlling the acquisition of neuronal identity, diversity, and connectivity in the formation of …

Launching The Next Generation : Transcriptional Regulation During Oogenesis, Alicia K. Mccarthy

Legacy Theses & Dissertations (2009 - 2024)

Germ cells give rise to gametes and link generations by passing genetic information from parent to offspring. Gametes arise from, in many sexually reproducing organisms, germline stem cells (GSCs) which are set aside early during development. GSCs have an amazing capacity to undergo self-renewal to give rise to a pool of undifferentiated cells, while also differentiating to generate specialized germ cells such as haploid gametes. Upon female GSC differentiation, mitotically dividing germ cells can initiate meiosis, and mature within a follicle. During maturation, the specified oocyte is provided with a trust fund of RNAs and proteins for the next generation …

The Influence Of Mir-322 On Skeletal Muscle Differentiation, Miles Alexander Soyer

Legacy Theses & Dissertations (2009 - 2024)

Skeletal muscle plays a crucial role in coordinating voluntary movement and accounts for nearly 50% of total body mass. Dysregulation in skeletal muscle development is known to cause muscle degenerative diseases including the devastating Duchenne Muscular Dystrophy (DMD). The majority of the biological studies investigating muscle development were based on myogenic transcription factors and signaling molecules including: Pax7, Myf5, MyoD, WNT, TGF-β and BMP. After the discovery of non-coding RNAs including microRNAs, it was postulated that these molecules could regulate gene expression and thus affect differentiation and development. MicroRNAs are small non-coding RNAs (~17-25 nucleotides) that regulate gene expression negatively …

The Role Of Rock Signaling On Salivary Gland Organoid Formation, Matthew Koslow

Legacy Theses & Dissertations (2009 - 2024)

Salivary glands are crucial organs that are responsible for secreting saliva which is important for the breakdown of carbohydrates, providing lubrication of the mouth, and maintenance of oral health. Patients diagnosed with Sjögren's Syndrome or receiving treatment for head and neck cancer, can permanently lose salivary gland function, which is referred to as salivary hypofunction. As a result, these patients develop Xerostomia, or the feeling of dry mouth, and suffer from an overall decreased quality of life. To combat the negative effects of salivary hypofunction, stem cell therapy is an attractive option, as implantation of specific cell populations can rescue …

Of Donuts And Promo : In Silico Approaches To Identification Of Transcriptional Regulators Of Salivary Acinar Differentiation, Connor Cillian Duffy

Legacy Theses & Dissertations (2009 - 2024)

The salivary gland is an organ often taken for granted by most people. However, its proper function is essential for several everyday activities, such as speaking, swallowing, and tasting. As such, impaired salivary gland function, such as that caused by Sjögren’s Syndrome or radiotherapy for head and neck cancers, can lead to a significantly reduced quality of life. The cells that produce saliva in salivary glands are known as acinar cells, which arise from proacinar cells generated during embryonic development. As such, in studying the promoter regions of proacinar and acinar genes, it may be possible to identify common transcription …

Modulation Of Cytokine Signaling In Optic Nerve Regeneration In Xenopus Laevis, Rupa Priscilla Choudhary

Legacy Theses & Dissertations (2009 - 2024)

The axons of the optic nerve, like other central nervous system (CNS) axons, tend to lose their capacity to regenerate following an injury in adult amniotes, but these axons are able to regenerate throughout life in anamniotes. In mammals, optic axon regeneration is promoted by inhibiting the increased expression in retinal ganglion cells of a cytokine signaling molecule, Suppressor of Cytokine Signaling 3 (SOCS3), that accompanies injury. In animals capable of regeneration, SOCS3 mRNA expression also increases dramatically in retinal ganglion cells after optic nerve injury, but somehow this increase is insufficient to block regeneration. To gain insights into how …

Regulated Transcriptional Silencing Promotes Germline Stem Cell Differentiation In Drosophila Melanogaster, Pooja Flora

Legacy Theses & Dissertations (2009 - 2024)

Germ cells are the only cell in an organism that have the capacity to give rise to a new organism and are passed from one generation to the next. Therefore, to maintain this unique ability of totipotency and immortality, germ cells execute specific functions, such as, repression of a somatic program and contour a germ line-specific pre- and post-transcriptional gene regulatory landscape. In many sexually reproducing organisms, germ cells are formed during the earliest stages of embryogenesis and undergoes several stages of development to eventually get encapsulated by the somatic cells of the gonad. Once, in the gonad, the germ …

Chromatin-Signaling Axis Orchestrates The Formation Of Germline Stem Cell Differentiation Niche In Drosophila, Maitreyi Upadhyay

Legacy Theses & Dissertations (2009 - 2024)

Stem cells have the unique capability of self-renewing into stem cells and differentiating into several terminal cell types. Loss of either of these processes can lead to aging, progression towards degenerative diseases and cancers. Insight into how self-renewal and differentiation are regulated will have tremendous therapeutic impact. Drosophila is an excellent model system for stem cell study due to the availability of various mutants, markers and RNAi technology. In order to study stem cell biology, we use female Drosophila gonads, whose stem cell population – the germline stem cells (GSCs) gives rise to gametes.

Retinoic Acid Receptor Isoform-Specific Control Of Mouse Salivary Gland Development And Regeneration, Kara Desantis

Legacy Theses & Dissertations (2009 - 2024)

Controlled expansion and differentiation of progenitor cell populations is essential for organogenesis followed by continued maintenance of the population into and through adulthood. As the K5+ basal cell population is regulated by retinoic acid signaling, we interrogated the contribution of specific RAR isoforms to the regulation of these cells during submandibular salivary gland (SMG) organogenesis and regeneration. Retinoic acid has previously been shown to be involved in the development of the salivary gland, and recently, lack of retinoid signaling has been shown to impact the K5+ population of basal progenitor cells. Since retinoic acid is known to exert stimulatory effects …

The Role Of N-Myc Downstream Regulated Gene 1 In Breast Cancer Lipid Metabolism, Christopher James Sevinsky

Legacy Theses & Dissertations (2009 - 2024)

Altered carbohydrate and lipid metabolism are increasingly well characterized hallmarks of aggressive breast cancers. While aerobic glycolysis, or “the Warburg effect”, is a well-established metabolic adaptation exploited by tumor cells, the understanding of unique aspects of cancer lipid metabolism lags behind. This is especially true regarding the coordination of complex lipid synthesis and trafficking pathways, which remains poorly understood. N-Myc Downstream Regulated Gene1 (NDRG1) is overexpressed in many solid tumors, but its function is unclear. The importance of NDRG1 is best exemplified by the effect of null mutations on human physiology: inactivating mutations give rise to the severe autosomal recessive …

Understanding The Genotoxicity Of Silver Nanoparticles And The Chemoprevention Of Pomegranate Extract, Sameera Nallanthighal

Legacy Theses & Dissertations (2009 - 2024)

The use of silver nanoparticles (AgNPs) in a wide variety of consumer products (i.e. toothpastes, food containers, dietary supplements and garments) for their antimicrobial properties can lead to potential oral exposure in humans. To enhance their stability, AgNPs are coated with capping agents such as citrate and polyvinylpyrrolidone (PVP). Despite the lack of significant general toxicity based on hematology, blood chemistry and histology evaluations, the potential genotoxic effects of AgNPs cannot be ruled out and have to be addressed. Studies examining the genotoxic risks of AgNPs are needed because genotoxicity is a strong indicator of cancer risk. Here we examined …

Brown Adipogenesis Of Mouse Embryonic Stem Cells In Alginate Microstrands, Andrea Mannarino Unser

Legacy Theses & Dissertations (2009 - 2024)

The ability of brown adipocytes (fat cells) to dissipate energy as heat shows great promise for the treatment of obesity and other metabolic disorders. Employing pluripotent stem cells, with an emphasis on directed differentiation, may overcome many issues currently associated with primary fat cell cultures. However, brown adipocytes are difficult to transplant in vivo due to the instability of fat, in terms of necrosis and neovascularization, once injected. Thus, 3D cell culture systems that have the potential to mimic adipogenic microenvironments are needed, not only to advance brown fat implantation, but also to better understand the role of brown adipocytes …

Myoepithelial Cell Morphogenesis And Differentiation In The Mouse Submandibular Salivary Gland In Development And Disease, Elise Marie Gervais

Legacy Theses & Dissertations (2009 - 2024)

Organogenesis is the process by which tissues organize, gain considerable size, and undergo cellular differentiation or specialization to form fully functional organs. To study the processes involved in organogenesis of branched organs, the mouse submandibular salivary gland is frequently used as a model system, as it can undergo morphogenesis and differentiation and be genetically manipulated ex vivo. The mouse submandibular salivary gland undergoes a specific process of outgrowth and invagination known as branching morphogenesis which allows for the significant increase in gland size and complexity, as well as maximization of surface area for secretion of saliva. Surrounding the mouse submandibular …

A Novel Method For Studying Gene Regulatory Elements In Vivo Reveals Essential Roles For Intron Splicing In Neurofilament Gene Expression, Chen Wang

Legacy Theses & Dissertations (2009 - 2024)

Axon outgrowth requires coordinated expression of critical cytoskeletal genes in response to extracellular cues. The spatial and temporal expression of these genes is regulated transcriptionally and posttranscriptionally. Such regulation is largely mediated through the activity of cis-regulatory elements within the cytoskeletal DNAs and RNAs, which recruit specific sets of trans-factors such as DNA- and RNA-binding proteins, as well as microRNAs. To identify the functionally active cis-elements, characterize their dynamically changing sets of trans-factors, and investigate the association between the two sets of regulators in the context of an intact developing nervous system, one needs to combine appropriate in vivo strategies …

Vitamin D Signaling And The Impact On Mouse Mammary Gland Epithelium, Donald Grant Matthews

Legacy Theses & Dissertations (2009 - 2024)

A strong correlation between vitamin D deficiency and increased breast cancer incidence and mortality has been well established, leading researchers to further examine the possibility of using vitamin D in treatment and prevention strategies. Our long term goal is to elucidate the mechanisms by which vitamin D pathway signaling impacts on breast cancer. Generation of the high-affinity vitamin D receptor (VDR) ligand 1,25-dihydroxyvitamin D (1,25-D) from 25-hydroxyvitamin D (25-D) is mediated by CYP27B1 which is present and developmentally regulated in multiple tissues including the mammary gland. We utilized transgenic mouse models combined with diet-induced vitamin D deficiency to determine whether …