Digital Commons Network^™

Analysis Of Spore Shape Determination In Streptomyces, Ning Sun

Electronic Theses and Dissertations

Streptomycetes are Gram-positive, soil-dwelling bacteria that possess a complex life cycle with the alternation of vegetative mycelium, aerial mycelium, and spores. Streptomyces. coelicolor spore maturation is a complex process that involves spore shape metamorphosis from cylindrical pre-spores into ellipsoid spores, but the details of this process have remained enigmatic. Previously, our lab identified a novel gene ssdA that might play a role in spore shape determination using a transposon-based insertion mutagenesis in S. coelicolor. In this study, I isolated a S. coelicolor ssdA-null mutant that showed increased colony hydrophobicity and misshapen spores in sizes and shapes, confirming the …

Molecular Investigation Into The Biologic And Prognostic Elements Of Peripheral T-Cell Lymphoma With Regulators Of Tumor Microenvironment Signaling Explored In Model Systems, Tyler Herek

Theses & Dissertations

Peripheral T-cell lymphoma (PTCL) is heterogenous group of mature T-cell neoplasms characterized by distinctive transcriptional and genetic lesions. Herein, we investigated DNMT3A mutations in angioimmunoblastic T-cell lymphoma (AITL, n = 176) and novel molecular subtypes (i.e., PTCL-GATA3, n = 61 and PTCL-TBX21, n = 80) within PTCL- NOS and observed significant biological and prognostic differences associated with DNMT3A mutations. DNMT3A-mutated PTCL-TBX21 cases showed inferior overall survival (OS; p < 0.005), with DNMT3A mutations (DNMT3A-MT) skewed toward the methyltransferase domain and in the dimerization domain (S881-R887). Transcriptional profiling demonstrated significant enrichment of activated CD8⁺ T-cell cytotoxic gene signatures in the tumor microenvironment of DNMT3A-MT PTCL-TBX21 cases. Genome-wide methylation analysis of DNMT3A-R882/Q886 versus wild-type in PTCL-TBX21 cases demonstrated hypomethylation in target genes regulating T-cytotoxic genes, TCR …

Identifying And Knocking Out Non-Visual Opsins In The Optic Tectum Of Zebrafish Larvae, Sarah Jarrett

Undergraduate Honors Theses

Deep brain photoreceptors (DBPs) are non-visual photoreceptors found in the brains of non-mammalian vertebrates like zebrafish. While using optogenetic techniques in our lab to photo-activate the ear (by expressing the light-gated channel: channelrhodopsin) in efforts of identifying optic tectum (OT) neurons that respond to and integrate auditory and visual stimuli, we found that violet light was able to elicit OT neuronal activity. OT activity was also detected in cases when visual and auditory stimulation was not possible due to removal of the eyes and absence of the exogenously expressed channelrhodopsin, respectively. Analyzing OT single-cell sequencing data of 7day post fertilization …

Nuclear Receptor Coactivator 3 In Endoplasmic Reticulum Stress And Stress Granule Dynamics In Pancreatic Cancer, Andrew Kisling

Theses & Dissertations

Pancreatic cancer is predicted to be the second-leading cause of cancer-related deaths within the next decade. Nuclear receptor coactivator 3 (NCOA3/SRC3/AIB1) regulates an array of metabolic and signaling pathways and has been established by our group and others as a critical regulator pancreatic cancer progression and metastasis. A recent study demonstrated NCOA3 regulation by the IRE1α-XBP1 axis of the unfolded protein response (UPR), suggesting a link between NCOA3 and cellular stress management. Furthermore, NCOA3 has been shown to directly bind to a scaffolding protein of stress granules (SGs). Since SG assembly is regulated by the UPR, we hypothesized that NCOA3 …

A Pkcα-Mediated Growth Suppressive Mek-Erk Signaling Axis In Intestinal Epithelial Cells, Navneet Kaur

Theses & Dissertations

Members of the protein kinase C (PKC) family of serine/threonine kinases are involved in regulation of fundamental cellular functions, including proliferation, differentiation, survival, migration, and transformation. Increasing evidence points to anti-proliferative and tumor suppressive role of PKCs. Our laboratory and others have reported that the classical PKC isozyme, PKCαnegatively regulates proliferation and tumorigenesis in the intestinal epithelium. Our laboratory has further determined that PKCα signaling induces a program of cell cycle withdrawal in intestinal epithelial cells that involves downregulation of the pro-proliferative proteins, cyclin D1 and Id1, and upregulation of the cyclin dependent kinase (CDK) inhibitor, p21^Cip1. Unexpectedly, …

Usp11 And Usp7 Deubiquitinases Regulate Sprtn Auto-Proteolysis And Sprtn-Mediated Dna-Protein Crosslink Repair, Megan C. Perry

Theses & Dissertations

DNA repair pathways that recognize and remove damaged DNA are vital for maintenance of genomic stability and prevention of tumorigenesis. Conversely, these pathways may be robust in tumor cells, thus diminishing the anti-cancer potential of available therapies. DNA-protein crosslinks (DPCs) are particularly deleterious DNA adducts that occur when proteins become irreversibly covalently bound to the DNA. DPCs represent a diverse group of lesions, as any protein can be crosslinked to the DNA duplex by non-specific crosslinking agents like reactive aldehydes and radiation. Additionally, functional DNA-binding proteins such as topoisomerases may become permanently crosslinked to DNA ends by abortive enzymatic processes …

Development Of A Muc16-Targeted Near-Infrared Antibody Probe For Fluorescence-Guided Surgery Of Pancreatic Cancer, Madeline T. Olson

Theses & Dissertations

Pancreatic cancer (PDAC) is an extremely lethal disease with an overall survival rate of 10%. Surgery remains the only potentially curative treatment option, but resections are complicated by infiltrative disease, proximity of critical vasculature, peritumoral inflammation, and dense stroma. Surgeons are limited to tactile and visual cues to differentiate cancerous tissue from normal tissue. Furthermore, translating preoperative images to the intraoperative setting poses additional challenges for tumor detection, and can result in undetected and unresected lesions. Thus, PDAC has high rates of incomplete resections, and subsequently, disease recurrence. Fluorescence-guided surgery (FGS) has emerged as a method to improve intraoperative detection …

Functional Characterization Of Cancer-Associated Dna Polymerase Ε Variants, Stephanie R. Barbari

Theses & Dissertations

Replicative DNA polymerases ε (Polε) and δ (Polδ) achieve high fidelity DNA synthesis through a precise balance of polymerization and exonucleolytic proofreading. Errors that escape proofreading are corrected by DNA mismatch repair (MMR). Ultramutated human cancers with proficient MMR carry alterations in the exonuclease domain of Polε, which were initially predicted to abolish proofreading. However, functional studies in yeast of the most recurrent Polε-P286R variant suggested defects beyond a loss of exonuclease activity. Indeed, biochemical analysis of the yeast Polε-P286R analog revealed increased polymerization capacity in addition to decreased proofreading, which enables efficient mismatch extension and bypass of replication-blocking non-B …

Probing The Role Of Astrocytes In The Pathology Of Fragile X Syndrome With Human Stem Cells, Baiyan Ren

Theses & Dissertations

Fragile X syndrome (FXS) is an X-linked neurodevelopmental disorder related to intellectual disability and the most common monogenic cause of autism spectrum disorder. FXS is mainly caused by an expansion of CGG repeats in the 5’-untranslated region of fragile X mental retardation 1 (FMR1) gene, leading to the loss of expression of fragile X mental retardation protein (FMRP). Astrocytes are the most abundant glial cells in the central nervous system (CNS). Loss of FMRP in astrocytes has been found to contribute to structural and functional synaptic deficits in the Fmr1-KO mouse model. The contribution of human astrocytes, however, to the …

Molecular Mechanisms Of Aberrant Protein Glycosylation In Pancreatic Cancer Stemness And Metastasis, Frank Leon

Theses & Dissertations

A myriad of genetic and other abnormal changes underlies the aggressiveness and dissemination properties observed in pancreatic cancer (PC). Aberrant protein glycosylation is a commonly observed feature in PC. The modification of protein O-glycosylation is mediated by glycosyltransferases, which attach and sequentially elongate monosaccharides on Serine/Threonine (Ser/Thr) motifs. Aberrant glycosylation is recognized as an emerging hallmark of cancer where a disruption in normal glycosylation results in irregular O-glycans.

This dissertation research has investigated the consequences of aberrant protein glycosylation on stemness and enhancement of metastatic properties in pancreatic ductal adenocarcinoma (PDAC). Several publications have reported aberrant O-glycosylation increases in oncogenic …

Investigating Antimicrobial Properties Of Snake Venoms Against B. Cereus, B. Subtilis, E. Coli, And P. Vulgaris, Savannah Berger

Honors Program Theses and Research Projects

The increasing incidence of antibiotic resistant bacterial infections has provoked the attention of health officials and scientists as a major threat to global public health. Antibiotic resistance is the product of overprescription by doctors, ineffective or shortened dosing by the patient, and more. When a bacterial infection is ineffectively treated as such, persistent pathogenic cells are given the opportunity to proliferate and spread their resistance to other cells. With bacteria utilizing such tools to fight and ultimately resist our current treatment methods, investigation towards the next novel mechanism of inhibition is essential. Venom is of particular interest to many scientists …

Regional Reprogramming And The Small Intestine: Analysis And Modeling Of Adaptive Regeneration Of The Epithelium, Sarah Elizabeth Waye

Arts & Sciences Electronic Theses and Dissertations

The small intestine in homeostasis is capable of regular regeneration, but in cases of massive injury like Short Bowel Syndrome, the innate human response often fails to fully compensate for the loss of nutrient absorptive surface area that accompanies bowel resection. Murine models display an active compensatory reaction deemed “adaptation” in which the surface area of the bowel is increased to accommodate nutrient absorptive needs. This observation has highlighted several gaps in knowledge regarding bowel adaptation. Firstly, what occurs on a molecular level in murine models during adaptation? Secondly, how can the findings in mice be applied to humans in …

Genetic Risk Factors For Neurodevelopmental Disorders: Insights From Hipsc-Cerebral Organoids, Michelle L. Wegscheid

Arts & Sciences Electronic Theses and Dissertations

Neurofibromatosis type 1 (NF1) is a common neurodevelopmental disorder (NDD) characterized by remarkable phenotypic variability, where affected children manifest a spectrum of central nervous system (CNS) abnormalities, including brain tumors, impairments in attention, behavior, learning disabilities, and an increased incidence of autism spectrum disorder (ASD). A significant barrier to the implementation of precision medicine strategies for children with NF1 is a lack of prognostic risk factors to guide clinical management. However, emerging population-based genotype-phenotype association studies have suggested that the germline NF1 gene mutation may represent one clinically actionable risk factor for NF1-associated neurodevelopmental abnormalities. As a critical step in …

Deep Multi-Omics Investigations Elucidate Novel Oncogenesis Paradigms, Therapeutic Targets, And Mechanisms Of Treatment Resistance In Cancer, Daniel Cui Zhou

Arts & Sciences Electronic Theses and Dissertations

No abstract provided.

Understanding The Kinomic Contributions To Tyrosine Kinase Inhibitor Resistance In Triple Negative Breast Cancer, Cory Lefebvre

Electronic Thesis and Dissertation Repository

Resistance to tyrosine kinase inhibitors (TKIs) presents a growing challenge in the development of therapeutic targets for cancers such as triple negative breast cancer (TNBC), where conventional therapies are ineffective at combatting systemic disease. Potential targets in TNBC include the receptor tyrosine kinases EGFR (epidermal growth factor receptor) and c-Met, however, targeted anti-EGFR and anti-c-Met therapies have faced challenges in clinical trials due to acquired resistance. We hypothesize that response versus resistance of triple negative breast cancer to the tyrosine kinase inhibitors erlotinib and cabozantinib is mediated by compensatory changes in the kinome and phosphoproteome. To test this, we (1) …

Antimicrobial Activity Of Bacterial Virus Components: An Empirical Investigation Of The Killing Capacity Of Toxins From Burkholderia, Kyle Walny

Honors Projects

Given the growing issue in healthcare of antibiotic resistance, effective and safe alternative treatment methods are required. One of these possible alternative treatment methods is bacteriotoxins including bacteriocins and tailocins. The focus of this study is a bacteriotoxin from Burkholderia cenocepacia (ATCC 25608), which was induced for toxin using a modified UV light induction procedure and tested against a variety of Pseudomonas and Burkholderia for its killing capacity. Various other pathogenic strains were then induced with UV light and tested. The results showed that the toxin from ATCC 25608 was very effective against most of the Burkholderia tested and warrants …

An Insider's Guide To Cell Biology, Katie Ludwig

Honors Projects

An Insider's Guide to Cell Biology is a comic book that follows Alanine the amoeba who tells the reader all about how the cell works.

Dicer Represses Antiviral Innate Immunity Pathways In Mouse Embryonic Stem Cells, Chandan Gurung

Dissertations

Recent studies have demonstrated that embryonic stem cells (ESCs) are deficient in expressing type I interferons (IFN), the cytokines that play key roles in antiviral responses. However, the underlying molecular mechanisms and biological implications of this finding are poorly understood. In this study, I used a synthetic RNA-based assay that can simultaneously assess multiple forms of antiviral responses in ESCs. Dicer is an enzyme essential for RNA interference (RNAi), which is used as a major antiviral mechanism in invertebrates but not clear in vertebrates. RNAi activity is detected in wild-type ESCs but is abolished in Dicer knockout ESCs (D−/−ESCs) as …

Metabolic Regulation During Extraembryonic Endoderm Differentiation, Mohamed Gatie

Electronic Thesis and Dissertation Repository

The inner cell mass undergoes orchestrated cellular divisions resulting in the formation of the epiblast (EPI) and primitive endoderm (PrE). Understanding the process of cell fate specification is crucial to appreciate the intricacies of proper embryonic development. While the mouse embryo is an excellent model, limitations do exist with number, technical challenges, and accessibility, therefore, in my thesis I employed two cell-based models to recapitulate the EPI-PrE fate in vitro. Many signaling pathways have been implicated in this lineage decision, metabolism and its downstream products have been recently regarded as a driver of lineage commitment. Using various biochemical, molecular, …

The Effects Of Chronic Ethanol Exposure On Caenorhabditis Elegans Germline, Andrea Zegarra

Seton Hall University Dissertations and Theses (ETDs)

Ethanol is the most commonly abused drug in the world. Alcohol consumption increases a number of health risks, morbidity and mortality, and chronic and acute diseases. Some health risks include high blood pressure, stroke, liver disease, cancer, and can include mental health and social problems. Chronic alcohol consumption can lead to learning and memory problems, along with alcohol dependence. Additionally, alcohol consumption has an impact on ovarian reserve, steroid hormone production, sperm quality, fecundity, and fertility treatments. The purpose of this study was to analyze the effects of ethanol exposure on fertility of the N2 wild type as measured by …

Kindlin-1 Is Involved In Spreading, Migration, And Protein Regulation In Epidermal Scc-13 Cells, Naomi Mishan

Electronic Thesis and Dissertation Repository

Kindlin-1 is a scaffold protein linking the cytoskeleton to the extracellular matrix. Loss of function mutations in the FERMT1 gene (encoding Kindlin-1) cause gastrointestinal and skin defects associated with increased susceptibility to aggressive epidermal squamous cell carcinoma (SCC). This study investigated the consequences of targeted FERMT1 inactivation in the SCC-13 cell line of epidermal SCC. My studies demonstrate Kindlin-1 is not essential for SCC-13 proliferation or clonogenic potential in culture. Kindlin-1 was required for cell spreading on collagen I, but not on laminin-332, and its absence enhanced SCC-13 directional migration. Finally, I identified several proteins involved in tumor formation and …

Calmodulin Like 38 Is Required For Autophagy Of Hypoxia-Induced Cytoplasmic Rna Granules In Arabidopsis Thaliana, Sterling Field

Doctoral Dissertations

In response to the energy crisis resulting from submergence stress and hypoxia, the model plant Arabidopsis thaliana limits non-essential mRNA translation, and accumulates cytosolic stress granules. Stress granules are phase-separated mRNA-protein particles that partition transcripts for various fates: storage, degradation, or return to translation after stress alleviation. Another response by the plant cell to low oxygen stress is the induction of the turnover pathway autophagy. Stress granule regulation by autophagy occurs by a ‘granulophagy’ pathway in yeast and mammalian systems through which parts or whole stress granules are degraded. Whether this occurs in plants has not been investigated.

A connection …

Erecta Family Genes Regulate The Shoot Apical Meristem And Organ Formation, Daniel A. Degennaro

Doctoral Dissertations

Plants are sessile and must adjust their organ growth to their environments. A reservoir of stem cells in the shoot apical meristem (SAM) supplies cells for differentiation into organs. The SAM must balance organ production with stem cell maintenance. The ERECTA family (ERfs) encodes the leucine-rich repeat receptor-like kinases ERECTA (ER), ERECTA-LIKE 1 (ERL1), and ERL2. ERf signaling regulates organ initiation and stem cell maintenance. Results presented in this work include the following:

1) WUSCHEL (WUS) and CLAVATA3 (CLV3) make up a negative feedback loop to maintain SAM size. WUS and CLV3 expression localization is critical for …

Osmr Signaling Induces Tamp-Specific Bbb Dysfunction Following Autoimmune-Mediated Neutrophil Recruitment, Travis Scott Wertz

Boise State University Theses and Dissertations

Integrity of the brain microvessels that form the blood-brain barrier (BBB) is maintained through fine-tuned regulation of endothelial tight junction proteins, chiefly represented by claudin 5 and the tight junction-associated MARVEL protein (TAMP) occludin. Under proinflammatory conditions in autoimmune-mediated multiple sclerosis (MS), autoreactive effector T cells are activated in white matter regions of the brain and spinal cord and release cytokines to recruit circulating neutrophils that, in turn, release neurotoxic substances. Lack of tight junctions in peripheral blood vessels allows neutrophils to exit blood vessels unhindered, but BBB tight junctions must first be downregulated before neutrophils can transmigrate into the …

Differentiating The Mechanistic Role And Chemotherapeutic Potential Of Src And Podoplanin In Oncogenic Transformation, Edward P. Retzbach

Graduate School of Biomedical Sciences Theses and Dissertations

There were an estimated 20 million new cancer cases worldwide in 2020, resulting in nearly 1000 deaths per hour [1]. Oral cancer exemplifies the difficulties of treating cancer patients. The first line for oral cancer treatment is surgery and radiation that can lead to patient disfigurement and decreased quality of life in cancer survivors [2-4]. Though there have been many developments in chemotherapy in the last 30 years, the 50% mortality rate associated with oral cancer has not changed [4, 5]. Longitudinal studies that track survival rates in oral cancer patients demonstrate a 3-fold reduction in patient deaths when patients …

Gene Regulatory Mechanisms Driving Cellular Reprogramming For Successful Optic Nerve Regeneration In Zebrafish, Sumona Pareshnath Dhara

Theses and Dissertations

Mammalian retinal ganglion cells (RGCs) in the central nervous system (CNS) often die after trauma to the optic nerve by either injury or disease. The surviving RGCs fail to regenerate their axons, eventually resulting in irreversible vision loss. Therefore, the functional restoration of eye-to-brain pathways is a significant challenge in the field. Unlike mammals, adult fish can fully regenerate CNS axons, enabling functional recovery from optic nerve damage. Both fish and mammals normally undergo a developmental down-regulation of axon growth activity as neurons mature. Fish are able to undergo damage-induced “reprogramming” through re-expression of genes necessary for axon growth and …

Lgr5 Regulation Of Stat3 Signaling And Drug Resistance In Colorectal Cancer, Tressie Posey, Tressie Alexandra Posey

Dissertations & Theses (Open Access)

LGR5 Regulation of STAT3 Signaling and Drug Resistance in Colorectal Cancer

Tressie Alexandra Capri Posey B.S.

Advisory Professor: Kendra Carmon, Ph.D.

The greatest difficulty in treating colorectal cancer (CRC) is the development of drug resistance which leads to relapse after treatment and progression to metastasis. Cancer stem cells (CSCs) are believed to drive relapse because of their capacity to self-renew, acquire resistance mechanisms, and differentiate promoting tumor growth and heterogeneity. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), is a bona-fide marker of CSCs and has been considered a viable target for CSC specific therapeutic development. While we showed targeting LGR5 …

Mutant Kras Alters Extracellular Vesicle Microrna Sorting In Pancreatic Cystic Neoplasms, Rachel L. Dittmar

Dissertations & Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers by organ site with a 5-year survival rate of just 10.8%. This is largely because most patients do not experience symptoms until the disease has already metastasized. The best hope to cure PDAC is surgery, which can only be done with a curative intent at an early stage when the disease is localized. There are no reliable circulating, body-fluid-based biomarkers to detect early stage PDAC or its precursor lesions in a timely manner for effective surgical intervention. When potential PDAC precursor lesions, such as mucinous pancreatic cysts are found, there are …

Evaluating The Biological Activities Of Novel Histone Deacetylase Inhibitors (Hdaci) In Adherent And Nonadherent Tumor Cell Lines, Samer Alanani

Theses and Dissertations

Epigenetic dysregulations are linked to many human diseases including neurodegenerative disorders, immunodeficiencies, cardiac disease, and most notably cancer. Changes in the mechanisms of histone modifications have been recognized as hallmarks of carcinogenesis. One of these modifications is histone acetylation which is regulated by the activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). The reversible actions of these enzymes govern the acetylome and maintain its balance allowing for activation and repression of gene transcription. However, aberrant overexpression of HDACs in certain tumors is associated with decreased levels of transcription leading to tumor progression and survival. Hence, small-molecule histone deacetylase inhibitors …

The Role Of The Erbb Signaling Pathway In Cardiovascular Progenitor Cell-Based Repair, Christopher Ramos

Electronic Theses, Projects, and Dissertations

Adult mammalian hearts lack self-renewal and proliferative capabilities necessary for cardiovascular regeneration. Current treatments using cardiac progenitor cells (CPCs) for cell-based repair do not restore cardiac function in patients who experience a myocardial infarction (MI). Our laboratory has been studying Islet-1+ neonatal CPCs as a promising candidate for cell-based repair due to their ability to significantly improve cardiac function after MI in sheep. The current study addresses the hypothesis that the ERBB pathway is linked to the Hippo-pathway to activate YAP1 by the involvement of an autocrine loop that upregulates neuregulin (NRG). In our sheep model of MI and cardiovascular …