Cell and Developmental Biology Commons^™

Thymidine Phosphorylase Is A Promising Target In Sars-Cov-2 Spike Protein-Enhanced Thrombosis, Renat Roytenberg

Theses, Dissertations and Capstones

Thrombosis, as an underlying mechanism in cardiovascular diseases, is the leading global cause of death in the 21st century. Infection is a risk factor for thrombosis, and the coronavirus disease 2019 (COVID-19) pandemic has led to a rise in the incidence of thrombosis, thereby increasing mortality. In comparison to previous severe coronavirus outbreaks, rates of thrombosis in COVID-19 have been unprecedented. COVID-19 is caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 spike protein (SP), the key used to enter host cells, is implicated in thrombosis pathology, though mechanisms are not fully understood. The SARS-CoV-2 …

The Effects Of Bisphenol S On Glial Cells Of The Peripheral Nervous System, Madeline Solomon, Rachael Sennett, Angela Asirvatham

Student Research Poster Presentations 2024

Schwann cells are glial cells in the peripheral nervous system that maintain nerve function and myelination. Peripheral nerve myelination is dependent on intact Schwann cell proliferation. Schwann cell proliferation can be adversely affected by environmental pollutants such as Bisphenol A (BPA). BPA is an endocrine-disrupting chemical found in plastic water bottles, receipt paper, containers, and many everyday products. Studies on BPA exposure showed that it stimulated cellular proliferation in neural stem cells. A commonly used manufactured derivative of BPA, Bisphenol S (BPS), has posed similar concerns. Previous research has found that BPS promotes the proliferation of MCF-7 breast cancer cells …

The Effects Of Bpf On Rt4 Schwannoma Cancer Cells, Rachael Sennett, Madeline Solomon, Angela Asirvatham

Student Research Poster Presentations 2024

Bisphenol A is a harmful compound common in plastics that causes negative health and environmental effects. Due to these effects, new guidelines have been made to limit exposure to BPA. However, modified versions of these compounds, including Bisphenol-F, are being used as a replacement. Exposure to BPF, which is comparable in structure to BPA, has similar effects as BPA on many organ systems with some being unknown. As there is not much known about BPF, especially in the peripheral nervous system, the aim of this research is to analyze proliferation rates in BPF-treated Schwann cells. It was hypothesized that with …

Assessing The Role Of Kmt2b Knockdown In Rhabdoid Tumorigenesis Utilizing Crispri, Karah Edmonds, Andrea Florian Phd

Science University Research Symposium (SURS)

An aggressive blood cancer commonly observed in pediatric patients, Mixed Lineage Leukemia (MLL), has a regulatory MLL complex that promotes histone methyltransferation. Modifying histones utilizing histone methyltransferases like KMT2B (MLL2), is essential for gene expression by regulating transcription. Loss of function and inhibition of KMT2B leads to dysregulation of transcription and therefore promotes MLL tumorigenesis. To improve cancer-targeted therapies, we will use CRISPR interference (CRISPRi) to knock down the expression of KMT2B and measure levels of Rhabdoid tumor cell proliferation and apoptosis. Previous research surrounding the MLL complex suggests that decreased expression of KMT2B will lead to increased levels of …

Role Of Insulin-Like Growth Factor-1 Signaling In Diet-Enhanced Bone Elongation, Cassaundra A. White

Theses, Dissertations and Capstones

Childhood obesity has increased precipitously to the point that almost 20% of children between the ages of 2 and 19 have been diagnosed with obesity. While obesity is a complex metabolic disorder, one contributing factor is diet, particularly a diet high in fat. Among many problems associated with diet-induced obesity, the impact on skeletal health is often overlooked. In addition to increased stress on the skeleton due to excess weight, obesity also disrupts the endocrine and immune systems that, in turn, can secondarily alter skeletal growth. Obesity during the early years of childhood is particularly detrimental because the skeleton is …

A New Model For Polar Growth In Mycobacteria: The Role Of Wag31 And Mmpl3 In Cell Wall Synthesis, Neda Habibi Arejan

Biology Dissertations - Archive

The disease Tuberculosis (TB) is caused by the pathogen Mycobacterium tuberculosis and was the cause of over one million deaths worldwide in 2023 (World Health Organization, 2023). TB treatment is difficult due to antibiotic tolerance and emerging resistance in Mtb strains. Mycobacterial cells have different regulatory mechanisms that allow them to adjust to myriad environmental stressors: these responses often lead to antibiotic tolerance. Therefore, studying responses to stress will lead to insights about antibiotic tolerance and treatment failure. Here, we specifically study two essential mycobacterial proteins, Wag31 and MmpL3, involved in cell wall metabolism. We show that Wag31 has distinct …

Osteohistological Assessment Of Edmontosaurus Radii From The Liscomb Bonebed, Prince Creek Formation, North Slope, Alaska, Emma Griffin

Student Research Poster Presentations 2024

Hadrosaurs were one of the most diverse dinosaur groups in the Late Cretaceous period and are known for their numerous articulated skeletons and monodominant bonebeds (Wosik et al., 2020). They are more commonly known as duck-billed dinosaurs and are found globally including latitudinal extremes such as the artic and Antarctica. Edmontosaurus, a genus of hadrosaur, are herbivores and are very large growing up to 8,000 pounds. Edmontosaurus were known to travel in herds as a defense mechanism and were one of the last non-avian dinosaurs living during the late Campanian stage through the end of the Maastrichtian stage, right up …

Why Should Early-Career Scientists Publish In Society Journals, Stephen K. Dolan, Lori D. Banks, Wenqi Yu

Molecular Biosciences Faculty Publications

In this editorial, written by early-career scientists, we advocate for the invaluable role of society journals in our scientific community. By choosing to support these journals as authors, peer reviewers, and as editors, we can reinforce our academic growth and benefit from their re-investment back into the scientific ecosystem. Considering the numerous clear merits of this system for future generations of microbiologists and more broadly, society, we argue that early-career researchers should publish our high-quality research in society journals to shape the future of science and scientific publishing landscape.

The Inaugural Mbio Junior Editorial Board—Lessons Learned And The Path Forward Toward Improving The Peer Review Process, Cynthia Ayefoumi Adinortey, Stephen K. Dolan, Sarah Doore, Rebeccah Lijek, Diana Priscila Pires, Wenqi Yu, Elizabeth B. Draganova, Lennart Schada Von Borzyskowski

Molecular Biosciences Faculty Publications

The inaugural Junior Editorial Board (JEB) of mBio consisted of 64 early-career researchers active from 2022 to 2023. The goal of the JEB was to train early-career researchers in the art of peer review under the guidance of experienced editors. JEB members gained hands-on experience in peer review by participating in modules detailing the publishing process through the lenses of the journal, editor, and reviewer. Ultimately, JEB members applied this new knowledge by reviewing mBio manuscripts. Here, we summarize the background, the mission, and the achievements of the first mBio JEB. We also include possible trajectories for the future editions …

The Effects Of Secretion Regulators, Α-Synuclein And Cysteine String Protein-Α, In Thrombosis And Hemostasis, Alexis N. Smith

Theses and Dissertations--Molecular and Cellular Biochemistry

Platelets play many critical roles in the vasculature ensuring proper hemostasis and maintaining vascular integrity. They can mediate these different processes via the release of different cargo molecules from granules. Cargo release from the granules is mediated by a family of proteins called Soluble NSF Attachment Protein Receptors (SNAREs). This process is complex and is regulated by several protein-protein interactions that are not completely characterized. SNARE chaperones have been identified for the t-SNAREs such as Munc18b/STXBP2 for Syntaxin-11, but none have been identified for the VAMPs and SNAP proteins. Proteins of interest as potential chaperones for VAMPs and SNAP proteins …

Revolutionizing Our Understanding Of Specific Platelet-Pathogen Interactions, Hammodah Rawhi Hammodah Alfar

Theses and Dissertations--Molecular and Cellular Biochemistry

Aside from their classical role in maintaining hemostasis, platelets are considered first-line vascular guardians that influence both the innate and adaptive immune systems. This is mediated by either direct interactions with immune cells or through the release of pre-stored cytokines and chemokines upon interacting with pathogens such as viruses. While this establishes platelets as potential players in the response to pathogens, it remains unclear what platelets can do with pathogens and how important that is to immune responses, especially against viruses. Most systemic viremias, such as HIV-1, present with mild thrombocytopenia, which is mediated through several mechanisms such as a …

Calcium And Proteasomal Regulation Of Er-To-Golgi Protein Transport In Neurons, Samuel A. Galindo

Undergraduate Theses, Professional Papers, and Capstone Artifacts

Regulatory mechanisms of protein trafficking from the endoplasmic reticulum (ER) are critical to understand since neurodegenerative diseases involve defects in this process leading to chronic ER stress and cell death. This study aimed to better understand the calcium regulatory mechanisms of ER-to-Golgi trafficking in hybrid neuroglioblastoma cells (NG108). Specifically, we asked whether proteasomal degradation of transport machinery was involved in the previously demonstrated upregulation of ER-to-Golgi transport evoked by calcium signaling. Based upon previous literature, we believe that the calcium induced increase in transport is due to the activation of the calcium sensitive regulatory protein apoptosis linked gene 2 (ALG-2) …

Corals In Crisis: A Transcriptomic Investigation Of Stony Coral Tissue Loss Disease, Kelsey M. Beavers

Biology Dissertations - Archive

Coral reefs face existential threats due to climate change and human activities. The combined effects of ocean warming, overfishing, pollution, and habitat destruction have fundamentally altered the functionality of coral reefs and are driving a drastic increase in the prevalence and severity of coral disease outbreaks. Stony coral tissue loss disease (SCTLD) has emerged one of the most devastating disturbances to Caribbean reef ecosystems on record. Despite notable progress, the cellular mechanisms driving SCTLD pathogenesis remain poorly understood. To address this issue, my dissertation investigates the gene expression, histopathology, immune protein activity, and symbiont community dynamics involved in SCTLD progression …

Studying The Role Of Novel Carbon Nano Tubes As A Therapeutic Agent To Treat Triple Negative Breast Cancer (Tnbc) - An In Vitro And In Vivo Study, Kamal Asadipour, Narendra Banerjee, Jazmine Cuffee, Karrington Perry, Shennel Brown, Anasua Banerjee, Erik Armstrong, Stephen Beebe, Hirendra Banerjee

Bioelectrics Publications

Triple Negative Breast Cancer (TNBC) is a malignant cancer with a very high mortality rate around the world. African American(AA) women are 28% more likely to die from triple-negative breast cancer (TNBC) than white women with the same diagnosis. AA patients are also more likely to be diagnosed at a later stage of the disease and have the lowest survival rates for any stage of diagnosis; There are very few existing anti TNBC drugs with therapeutic efficacy hence newer anti TNBC drug design and investigation is needed. Carbon Nano Tubes(CNT) in recent years have shown effective anti-cancer properties in various …

Synergistic Effects Of Nanosecond Pulsed Plasma And Electric Field On Inactivation Of Pancreatic Cancer Cells In Vitro, Edwin A. Oshin, Zobia Minhas, Ruben M. L. Colunga Biancatelli, John D. Catravas, Richard Heller, Siqi Guo, Chunqi Jiang

Bioelectrics Publications

Nanosecond pulsed atmospheric pressure plasma jets (ns-APPJs) produce reactive plasma species, including charged particles and reactive oxygen and nitrogen species (RONS), which can induce oxidative stress in biological cells. Nanosecond pulsed electric field (nsPEF) has also been found to cause permeabilization of cell membranes and induce apoptosis or cell death. Combining the treatment of ns-APPJ and nsPEF may enhance the effectiveness of cancer cell inactivation with only moderate doses of both treatments. Employing ns-APPJ powered by 9 kV, 200 ns pulses at 2 kHz and 60-nsPEF of 50 kV/cm at 1 Hz, the synergistic effects on pancreatic cancer cells (Pan02) …

Multiple Variables Influence The Finely Calibrated Antioxidant Defenses Of Clostridioides Difficile, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The obligate anaerobe Clostridioides difficile encodes multiple reductases to detoxify molecular oxygen and reactive oxygen species. Caulat and colleagues have characterized the activity and regulation of four such reductases (L. C. Caulat, A. Lotoux, M. C. Martins, N. Kint, et al., mBio 15:e01591-24, 2024, https://doi.org/10.1128/mbio.01591-24). Each proved critical for clostridial survival in a different range of oxygen concentrations; together, they ameliorate a broad range of oxidative stress levels. Moreover, two previously uncharacterized regulators were found to control reductase gene expression in response to oxidative stress. The genetic repressor Rex and the reductase FdpF are both sensitive to the NAP …

Reprogramming Of Rat And Human Hepatoma Cells With Fibroblast-Specific Transcription Factors Msx1 And Pura, Merve Diler

Masters Theses

Despite all cells within an organism sharing the same genetic information, they develop into different tissues, each with a distinct gene expression profile required for tissue specialization. Understanding gene expression and the processes that regulate the expression, is crucial for understanding cell differentiation and tissue specialization, as these procedures are governed by unique gene expression and regulation patterns.

Whole genome microarray analyses identified several candidate genes that may be coding important transcription factors that play role in fibroblast identity such as Prrx1, Snai2, Shox2, Twist1, c-Fos, Msx1, Pdx1 (Idx1) and Pura (Pur1). The goal of this project is to determine …

Sphingosine Kinase 2 Depletion Dysregulates Hepatic Redox Metabolism And Enhances Inflammation In Early Metabolic Dysfunction-Associated Steatohepatitis (Mash), Kaitlyn Georgene Jackson

Theses and Dissertations

Metabolic dysfunction-associated steatotic liver disease (MASLD) currently affects one in three people worldwide; its prevalence is growing alongside other cardiometabolic disorders. Aberrations to redox and sphingolipid metabolism contribute to MASLD pathologic progression. Sphingosine-1-phosphate (S1P) is an active lipid, meaning that S1P participates in biochemical processes within the cell. S1P is generated by two distinct isoenzymes, sphingosine kinase (SphK)1 and SphK2. The localization of the SphK enzyme dictates S1P function. While cytosolic SphK1-generated S1P is well-characterized, nuclear and mitochondrial SphK2-generated S1P is less known. Moreover, SphK2 depletion effects on cellular redox processes and inflammation are not well-defined.

This study defines the …

Plk1 Overexpression Drives Tumorigenesis In A Prostate Cancer Mouse Model, Emile Kachouh

Theses and Dissertations

Prostate cancer is the leading cause of cancer-related deaths among men worldwide, and the development of resistance to existing treatments necessitates the exploration of new therapeutic strategies, including combination therapies. This study investigates the role of Polo-like kinase 1 (PLK1), located on chromosome 16p12.2, as an oncogene in prostate cancer. We generated a transgenic mouse model with prostate-specific overexpression of PLK1 to closely mimic human prostate cancer progression. Quantitative PCR (qPCR) analysis was employed to characterize the molecular profile of PLK1, revealing its implication in multiple pathways. To further elucidate the functional consequences of PLK1 overexpression, we confirmed phenotypic progression …

Investigating The Regulation Of Epithelial-Mesenchymal Transition Through Fibronectin-Mediated Tgf-Β1 Mechanotransduction Using In Vitro Models Of Triple-Negative Breast Cancer, Michael M. Sofroniou

Theses and Dissertations

TGF-β1 is a potent regulator of epithelial-mesenchymal transtion (EMT), a cellular
transdifferentation process that promotes cellular motility and matrix remodeling, critical to tumorigenesis and metastasis. TGF-β1-induced EMT promotes the assembly of FN, which synergistically binds latent TGF-β1 to aid in its activation. The purpose of of this work is to further probe the effects of autocrine TGF-β1 signaling during EMT progression by utilizing CRISPR-Cas9 deletion of the TGFB1 gene in in vitro models of triple-negative breast cancer. The studies outlined in this work demonstrate that autocrine TGF-β1 maintains a baseline level of mesenchymal marker expression. It also functions to desensitize …

An Updated Outline For Clearing And Staining Of Preserved Specimens, Sadie E. Smith

Honors Theses and Capstones

This protocol outlines a enhanced clearing and staining procedure for persevered specimens, focusing on the visualization of cartilage and bone in small taxa. With origins from O. Shultze's diaphonization methodology in 1897, the process of clearing and staining improves the clarity and contrast of intricate tissues. It is essential for studies in developmental biology, histology and anatomy. This protocol covers the key steps of the process while detailing the materials, solutions and estimated timeline for each step pertaining to specific taxa. The aim of the protocol is to standardize and provide guidance for procedures in the Biological Sciences department at …

Assessing Lipid Composition Of Cell Membrane In Escherichia Coli Under Aerobic And Anaerobic Conditions, Isabelle Johnson

Undergraduate Theses, Professional Papers, and Capstone Artifacts

Escherichia coli is a highly studied model organism that is tightly tied to the mammalian gastrointestinal system. This microorganism has the capability to be a beneficial gut microbe or a life-threatening pathogen. In this study, the lipid membrane of Escherichia coli was investigated using Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) to observe the change in its composition in aerobic and anaerobic conditions. Evidence of desaturation was discovered in the spectra, though more investigation is needed to understand the metabolic processes and drives that result in this change. Elucidation of these pathways in the future could result in …

The Effects Of The Clinically Relevant Synthetic Progestin, 17-Α-Hydroxyprogesterone Caproate, On Neural Development And Behavior., Paige L. Graney

Legacy Theses & Dissertations (2009 - 2024)

The synthetic progestin, 17-α -hydroxyprogesterone caproate (17-OHPC) has beencommonly prescribed during gestation to reduce preterm delivery in individuals at risk (Meis et al., 2003). In singleton pregnancies, 17-OHPC treatment begins during the second trimester, around gestational weeks 16-20, and continues until the end of the third trimester, around week 37 (Berghella, 2012). Although the fetus is not directly administered 17-OHPC, previous research demonstrated that 17-OHPC was transferred from the maternal unit to the fetal unit of the placenta in situ, was detectable in maternal and fetal blood up to 44 days following the last injection (Caritis et al., 2012; Hemauer …

Elucidation Of Mismatch Repair Regulation By Abl1: Advantages/Disadvantages Of Tyrosine Kinase Inhibitor Treatment, Hannah Daniels

Theses and Dissertations--Toxicology and Cancer Biology

DNA mismatch repair (MMR) is a critical repair process necessary for not only repairing mispairs incorporated into the DNA during replication, but also for inducing apoptosis in response to certain types of DNA damage. MMR is required for maintaining genomic integrity and due to the importance of this pathway, any impairment of its function can lead to increased mutation frequency, which is well known to be a driving force of cancer development, progression, and resistance. Despite extensive studies involving the proteins involved in the MMR pathway, the regulation of those proteins remains relatively unknown. Regulation of MLH1, a protein necessary …

Acquired Treatment Resistance In Prostate Cancer Via The Production Of Radiation Derived Extracellular Vesicles Containing Mitochondrial Proteins, Caitlin Miller

Theses and Dissertations--Toxicology and Cancer Biology

Radiation treatment (RT) is one of the most commonly administered treatments for prostate cancer (PCa) patients, yet the recurrence of tumors after RT remains one of the significant challenges in the eradication of PCa. In addition to induction of DNA damage, ROS production, and cell death, we found that RT promotes Extracellular vesicle (EV) production in PCa cells, at least in part, through H₂O₂ production (Miller CE et al., Antioxidants 2022, PMID 36358489). Since we observed EV production upon RT, EVs and their contents could play a role(s) in cancer survival after RT. By using flow cytometry …

Porcupine’S Role In The Enhancement Of Enzalutamide Efficacy In Drug Resistant Prostate Cancer, Katelyn Jones

Theses and Dissertations--Toxicology and Cancer Biology

Androgen receptor (AR) signaling continues to participate as a vital component of castration-resistant prostate cancer (CRPC). Subsequently, this has led to the development of Androgen Signaling Inhibitors (ASI), specifically Enzalutamide (ENZ), which is a direct inhibitor of AR, to clinically manage CRPC. Inevitably, ENZ treatment only provides improvement for approximately two months before advancing to an incurable form, ENZ-resistant CRPC. With PCa ranking as the second leading cause of cancer-related deaths in USA males, there is an urgency and necessity for the discovery and development of novel therapeutic approaches for CRPC. Wnt signaling has been extensively documented in its involvement …

Therapeutic Approaches And Novel Mechansims In Cancer Progression, Kendall Simpson

Theses and Dissertations--Toxicology and Cancer Biology

Prostate cancer (PCa) remains the most diagnosed cancer among men in the United States. There are various therapeutic routes that are implored to combat this fatal disease, and our work aims to increase the options made available to PCa patients. A combination treatment of Enzalutamide (Enz), an FDA approved drug for castration-resistant PCa patients, and Metformin, an FDA approved drug for type 2 diabetes, was utilized to enhance the efficacy of Enz in Enz-resistant PCa, both in vitro and in vivo. Thymic Lymphoma is one of the most common malignancies that can occur in various tissues and organs. Genomic stability …

Delineating Contributions Of Genotype And Lineage To Lung Cancer Therapy Response, Kassandra Jo Naughton

Theses and Dissertations--Toxicology and Cancer Biology

Non-small cell lung cancer (NSCLC) heterogeneity is a major challenge for determining effective treatment strategies. Adenocarcinomas (ADCs) and squamous cell carcinomas (SCCs) are histologically and epigenetically distinct subtypes of NSCLC. Patients with ADC tumors harboring mutations in both KRAS and LKB1 (aka STK11) have lower survival rates than those with KRAS-only tumors. KRAS/LKB1 tumors are not only aggressive, but also respond poorly to immunotherapy. However, these data are limited to ADCs, and it is unclear if SCCs with this genotype are also resistant to immunotherapy. We developed a mouse model of Kras^mut/Lkb1^mut capable of producing …

Dynamics Of Cell Membrane Lesions And Adaptive Conductance Under The Electrical Stress, Mantas Silkunas, Olga N. Pakhomova, Giedre Silkuniene, Andrei G. Pakhomov

Bioelectrics Publications

Exceeding physiological limits of the cell membrane potential compromises structural integrity, enabling the passage of normally impermeant solutes and disrupting cell function. Electropermeabilization has been studied extensively at the cellular scale, but not at the individual membrane lesion level. We employed fast total internal reflection fluorescence (TIRF) imaging of Ca(2+) entry transients to discern individual lesions in a hyperpolarized cell membrane and characterize their focality, thresholds, electrical conductance, and the lifecycle. A diffuse and momentary membrane permeabilization without a distinct pore formation was observed already at a -100 mV threshold. Polarizing down to -200 mV created focal pores with a …

Zebrafish Drug Screening Identifies Erlotinib As An Inhibitor Of Wnt/ Β-Catenin Signaling And Self-Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd A. Al-Hamaly, Anna H. Cox, Meghan G. Haney, Wen Zhang, Emma C. Arvin, Shilpa Sampathi, Mary Wimsett, Chunming Liu, Jessica S. Blackburn

Markey Cancer Center Faculty Publications

The Wnt/β-catenin pathway’s significance in cancer initiation, progression, and stem cell biology underscores its therapeutic potential. However, the clinical application of Wnt inhibitors remains limited due to challenges posed by off-target effects and complex cross-talk of Wnt signaling with other pathways. In this study, we leveraged a zebrafish model to perform a robust and rapid drug screening of 773 FDA-approved compounds to identify Wnt/β-catenin inhibitors with minimal toxicity. Utilizing zebrafish expressing a Wnt reporter, we identified several drugs that suppressed Wnt signaling without compromising zebrafish development. The effi- cacy of the top hit, Erlotinib, extended to human cells, where it …