Cell and Developmental Biology Commons^™

Fluorescence Probes For Bioimaging: Synthesis, Photophysical Properties And Applications, Mehrun Nahar Uddin

Dissertations

Fluorescent probes are a vital tool in the study of cell imaging. There are many types of fluorescent probes ranging from inorganic and organic nanoparticles to organic molecules. When used judiciously, they can help provide essential information on cellular structure and function. The introduction of two-photon microscopy has expanded the need for new probes, in particular near-infrared (NIR) absorbing and emitting fluorescent probes. The photochemical and photophysical properties of NIR probes play a crucial role in their effectiveness in cell imaging by both conventional and two-photon excitation (2PE) microscopy. In this research, the synthesis, photophysical properties, and two-photon absorption (2PA) …

Novel Biomarkers Of Ciliary Extracellular Vesicles Interact With Ciliopathy And Alzheimer’S Associated Proteins, Ashraf M. Mohieldin, Amal Alachkar, John R. Yates Iii, Surya M. Nauli

Pharmacy Faculty Articles and Research

Ciliary extracellular vesicles (ciEVs), released from primary cilia, contain functional proteins that play an important role in cilia structure and functions. We have recently shown that ciEVs and cytosolic extracellular vesicles (cyEVs) have unique and distinct biomarkers. While ciEV biomarkers have shown some interactions with known ciliary proteins, little is known about the interaction of ciEV proteins with proteins involved in ciliopathy and neurodegenerative disorders. Here, we reveal for the first time the protein-protein interaction (PPI) between the top five ciEVs biomarkers with ciliopathy and Alzheimer disease (AD) proteins. These results support the growing evidence of the critical physiological roles …

Induction Of Il19 Expression Through Jnk And Cgas-Sting Modulates Dna Damage–Induced Cytokine Production, Sara H. Small, E. Jessica Tang, Ryan L. Ragland, Yaroslava Ruzankina, David W. Schoppy, Rahul S. Mandal, M. Rebecca Glineburg, Zgjim Ustelenca, Daniel J. Powell, Fiona Simpkins, F. Bradley Johnson, Eric J. Brown

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Cytokine production is a critical component of cell-extrinsic responses to DNA damage and cellular senescence. Here, we demonstrated that expression of the gene encoding interleukin-19 (IL-19) was enhanced by DNA damage through pathways mediated by c-Jun amino-terminal kinase (JNK) and cGAS-STING and that IL19 expression was required for the subsequent production of the cytokines IL-1, IL-6, and IL-8. IL19 expression was stimulated by diverse cellular stresses, including inhibition of the DNA replication checkpoint kinase ATR (ataxia telangiectasia and Rad3-related protein), oncogene expression, replicative exhaustion, oxidative stress, and DNA double-strand breaks. Unlike the production of IL-6 and IL-8, IL19 expression was …

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 …

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 …

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 …

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 …

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, …

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 …

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 …

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 …

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 …

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 Elaine 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 …

Citric Acid/Β-Alanine Carbon Dots As A Novel Tool For Delivery Of Plasmid Dna Into E. Coli Cells, Anju Pandey, Asmita Devkota, Anil Sigdel, Zeinab Yadegari, C. Korsi Dumenyo, Ali Taheri

Agricultural and Environmental Sciences Faculty Research

Successful delivery of plasmid DNA into the microbial cells is fundamental in recombinant DNA technology. Natural bacterial transformation is limited to only certain species due in part to the repulsive forces between negatively charged DNA and bacterial membranes. Most common method of DNA delivery into bacteria is artificial transformation through heat shock and electroporation. These methods require sophisticated instruments and tedious steps in preparation of competent cells. Transformation by conjugation is also not applicable to all plasmids. Nanoparticles have been used successfully in therapeutics for drug delivery into animal cells. They are starting to gain popularity in plant sciences as …

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 …

Clinical Diagnosis Support With Convolutional Neural Network By Transfer Learning, Spencer Fogleman, Jeremy Otsap, Sangrae Cho

SMU Data Science Review

Breast cancer is prevalent among women in the United States. Breast cancer screening is standard but requires a radiologist to review screening images to make a diagnosis. Diagnosis through the traditional screening method of mammography currently has an accuracy of about 78% for women of all ages and demographics. A more recent and precise technique called Digital Breast Tomosynthesis (DBT) has shown to be more promising but is less well studied. A machine learning model trained on DBT images has the potential to increase the success of identifying breast cancer and reduce the time it takes to diagnose a patient, …

Role Of Sox18 In Promoting Tumorigenesis In Pediatric Cancer Cell Lines, Cherubina S. Rubannelsonkumar

Honors Program Theses and Research Projects

Sarcomas constitute a high percentage (∼13%) of cancer-related deaths among pediatric patients between 0-19 years of age, with Rhabdomyosarcoma (RMS) being the most common pediatric soft tissue sarcoma and Ewing Sarcoma being the second most common malignant bone tumor in children. Yet, survival for those who develop such metastatic sarcomas remains below 20-30%. Interestingly, SOX family proteins are known to be up regulated in various cancer types and play a role in cancer progression (tumorigenesis, metastasis, etc.). More specifically, targeted knockdown of SOX18 has been shown to suppress various tumorigenic properties in cancer cell lines including osteosarcoma cells, hepatocellular carcinoma …

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 …

Keratin 1 As A Cell-Surface Receptor In Cancer, Oluseye Ogunnigbagbe, Christopher G. Bunick, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Keratins are fibrous proteins that take part in several important cellular functions, including the formation of intermediate filaments. In addition, keratins serve as epithelial cell markers, which has made their role in cancer progression, diagnosis, and treatment an important focus of research. Keratin 1 (K1) is a type II keratin whose structure is comprised of a coiled-coil central domain flanked by flexible, glycine-rich loops in the N- and C-termini. While the structure of cytoplasmic K1 is established, the structure of cell-surface K1 is not known. Several transformed cells, such as cancerous cells and cells that have undergone oxidative stress, display …

The Effect Of Twist1b And Twist2 Knockdown On Tgf-Beta Signaling Expression In Tendon Progenitors, Marinia N. Bishay

Honors Scholars Collaborative Projects

Somites are important mesoderm structures that form in regularly timed intervals from the anterior end of the paraxial mesoderm at the end of gastrulation during embryogenesis. Cells of the ventromedial portion of the somite, the sclerotome, undergo epithelial to mesenchymal transition, surround the notochord, and give rise to connective tissues of the axial skeleton including the vertebrae, tendons, and ligaments. We are interested in understanding how the sclerotome is compartmentalized into the region that makes tendons. Genes expressed in the sclerotome, twist1 and twist2, are likely involved in the downstream differentiation of sclerotome to tendon progenitors. Previous studies have shown …

Novel Approaches For Enhancing Cell Survival And Function In Vivo, Ou Wang

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

FDA has approved several cell-based therapeutics and hundreds of cell therapy clinical trials are ongoing. Cells will be a significant type of medicine after small molecule and protein drugs. However, several obstacles need to be addressed to achieve the widespread use of cellular therapeutics. The first challenge is the low efficacy of cell transplantation due to low retention, survival, integration, and function of cells in vivo. The second challenge is producing a massive number of cells for clinical treatment with cost-effectively and reproducibly technologies.

In this thesis, we proposed and investigated two approaches to address these challenges. To begin …

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 …

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 …

College Of Natural Sciences Newsletter, December 2021, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Volume 2, Issue 12

Page 1 Dean's Message
Page 2 Awards & Recognition
Page 2 Media Coverage of CNS
Page 3 Media Coverage Cont.
Page 4 Science as Art Competition
Page 5 Open PRAIRIE Data
Page 5 Grants Awarded in CNS

Comprehensive Study Of Human Pathogenic Trypanosomatids: From Chemotherapies To Disease Ecology, Felipe Rodriguez

Open Access Theses & Dissertations

The vector-borne diseases Leishmaniasis and Chagas disease, caused by the kinetoplastid parasites Leishmania spp. and Trypanosoma cruzi respectively, are among the most important parasitic diseases in the group of neglected tropical diseases. Even though the two diseases are endemic to the Americas, they affect millions of people worldwide. Leishmaniasis and Chagas disease cause a great array of symptoms and some of them can be fatal if left undiagnosed and untreated. Current treatment regimens are becoming less effective, vaccines are still not available, and diagnosis needs to be improved. Vector control has been responsible for a decrease of diseases in endemic …

Co-Option Of The Yolkless Oocyte Receptor For Crispr/Cas9 May Induce Transient Sterility In Female Drosophila Grimshawi Flies, Bronwyn Miller

LSU New Orleans Theses and Dissertations

Evolutionary developmental biology has historically used generalist model organisms like Drosophila melanogaster. The Hawaiian Drosophilidae radiation, which occurred just 25 million years ago, is an ideal lineage for work in Evo-Devo. Hawaiian flies make up 25% of the world’s Drosophila species and extreme diversity is seen throughout the group. D. grimshawi is a generalist Hawaiian picture-wing fly that has served as a model for the Hawaiian Drosophilidae radiation. However, D. grimshawi’s power and use as a model organism is constrained by our lack of ability to manipulate its genome. In this work, I attempted to edit the genome of …

Engineering Fluorescently Labeled Human Fibroblast Growth Factor One Mutants And Characterizing Their Photophysics Properties Towards Designing Fret Assays, Mamello Mohale

Graduate Theses and Dissertations

Human fibroblast growth factor one (hFGF1) belongs to a family of 22 FGF members produced by fibroblast cells. Cell signaling during physiological processes of angiogenesis and wound healing occurs when hFGF1 binds to its receptor (FGFR). However, when heterogenous homeostasis is not maintained, fibroblast cells exhibit excessive proliferation which can lead to a myriad of cancers. smFRET is an ultrasensitive distant dependent (1-10 nm) technique capable of resolving such heterogeneity in structural dynamics and binding affinities (Kd). Therefore, we successfully designed and characterized fluorescently labeled hFGF1 tracers which span the visible light region of the electromagnetic spectrum for use in …

4d Ex Vivo Crispr/Cas9 Whole-Genome Screen To Identify Genes Regulating Lung Cancer Metastasis, Alexandria Plumer

Dissertations and Theses (Open Access)

Metastatic lung cancer has a 5-year survival rate of 5%. Lung cancers tend to be asymptomatic until late stages, and almost 90% are not diagnosed until they are advanced. Metastases are very rare events, often initiated by a single cell from a primary tumor into a new niche at a distant location. Investigation of the early metastatic process is of urgent need for the development of early diagnostics and targeted therapeutics. We performed a proof-of-concept CRISPR/Cas9 whole genome knockout screen in the A549 lung adenocarcinoma cell line and utilized a novel ex vivo 4D lung metastasis model to find gene …