Cell Biology Commons^™

Architects Of Mrna Fate: Molecular And Cellular Control Of P-Body Organization In The Drosophilia Melanogaster Female Germline, Samantha Milano

Dissertations, Theses, and Capstone Projects

Processing bodies (P-bodies) are cytoplasmic ribonucleoprotein condensates that regulate mRNA storage, translational repression, and decay. While the biochemical principles governing condensate assembly have been extensively studied in vitro, how P-body organization is established and dynamically regulated in vivo to control specific mRNA populations remains poorly understood. This dissertation investigated the molecular and cellular mechanisms that govern P-body architecture and function in the Drosophila melanogaster female germline. First, I identified the conserved LSm protein Trailer Hitch (Tral) as a central organizer of P-body architecture. Using quantitative confocal and super-resolution microscopy combined with chemical perturbations, I showed that Tral coordinates the …

Effect Of Partial Ablation Of Skeletal Dynamin Related Protein 1 On Mitochondrial Health, Inflammation, And Fibrosis In A Mouse Model Of Duchenne Muscular Dystrophy, Tessa L. Duzz

Graduate Masters Theses

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder characterized by muscle weakness, degeneration, fibrosis, and impaired muscle regeneration. Mitochondrial dysfunction is an early pathological feature of DMD and has been linked to excessive mitochondrial fission. Dynamin-related protein 1 (Drp1) is a central regulator of mitochondrial fission, a key process in regulating mitochondrial quality and function. Inhibition of Drp1-mediated mitochondrial fission has shown promise as a potential therapeutic target for alleviating pathology and dysfunction in dystrophic muscle. The objective of this study was to determine whether partial skeletal muscle-specific ablation of Drp1 could improve muscle pathology and mitochondrial health in …

Crosstalk Between Upr And Mitochondria: The Triad Of Er-Mitochondria Contacts, Ca²⁺, And Ros, Ester Zito, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Endoplasmic reticulum (ER) stress is triggered by several cellular perturbations causing protein misfolding, and activates the unfolded protein response (UPR), an initially adaptive signaling network that aims to restore ER and cellular homeostasis. Growing evidence indicates that UPR signaling extends beyond ER proteostasis, influencing mitochondrial function and bioenergetics through ER-mitochondria contact sites (ERMCs). The CHOP-ERO1A-IP3R axis has a primary role in recruiting mitochondria to adaptive UPR. However, its sustained activation renders UPR signaling maladaptive, leading to mitochondrial dysfunction through both outer mitochondrial membrane permeabilization (OMMP) and mitochondrial permeability transition pore (mPTP) opening, ultimately contributing to irreversible cell injury and disease …

The Role Of Seed Mix Characteristics And Soil Amendments During Post-Agricultural Prairie Restoration, Valerie N. Thurston, Michaela J. Woods, Madelaine Gregory, Mary C. Lloyd, Ryan W. Mcewan

Biology Faculty Publications

Introduction: Prairie restoration on degraded lands may be influenced by seed mix characteristics, including species richness and legume establishment. Soil amendments may facilitate restoration; however, the practical usefulness of techniques such as applications of whole soil and leaf mulch remains relatively unclear.

Objectives: We assessed whether increasing species richness and legume content in seed mixes enhances prairie restoration success and examined how soil amendments interact with seed mix composition to influence cover, species richness, diversity, and legume establishment.

Methods: We conducted a field experiment on a 12-ha post-agricultural site in Ohio, U.S.A. Twenty 50 × 50 m plots received one …

Three-Dimensional Cell And Nuclear Geometries Inform Tissue Level Fluid Mechanics During Epithelial Remodeling, Liam Joseph Russell

Electronic Theses and Dissertations

During epithelial remodeling, mechanical and molecular programs must coordinate to drive the cell shape changes that enable new tissue topologies. Dynamic morphogenesis requires epithelia to preferentially exhibit solid- or fluidlike properties depending on developmental and biophysical constraints. Convergent extension in the Drosophila germband epithelium is one such remodeling event, during which the lateral ectoderm lengthens by two-fold along the primary body axis while concomitantly shortening orthogonally. This process is an incredibly dynamic and attractable system for studying tissue morphogenesis mechanics in vivo.

Germband extension is driven by oriented cell intercalation through T1 transitions, where cells directionally interdigitate with one another …

Investigating Caveolar Systems: Spatiotemporal Quantification Of Caveolin-1 And The Mechanotransducive Function Of Ehd2, Jasper Stanae Farrington

Electronic Theses and Dissertations

Caveolae are 50-100nm cholesterol rich flask shaped invaginations found in many differentiated cells. Namely, these structures have been seen to be abundant in endothelial cells where they are involved in many signaling contexts. However, under mechanical stress, the characteristics of caveolae alter, flattening to increase membrane compliance, while displaced proteins can shift from structural roles to mechanosensitive signaling functions. Caveolin-1 (Cav1) is the principal protein required for Caveolar formation while Eps15 Homology Domain Containing Protein 2 (EHD2) is a membrane ATPase that acts to stabilize caveolae at the surface. Despite their emerging importance, understanding the organization and dynamic regulation of …

Exploring Foundations Of Animal Host-Microbe Interactions In A Freshwater Sponge, Jacob S. Pawley

Electronic Theses and Dissertations

The most ancient eukaryotic immune defense mechanisms evolved in unicellular species. Multicellular eukaryotes, however, expanded these mechanisms to meet challenges unique to multicellular life, including barrier formation, long-distance cell signaling, and coordinated responses that eliminate microbial threats while minimizing damage to the host. As such, animal immune signaling pathways are exceptionally intricate and diverse. Though, most of what is understood about animal host–microbe interactions stems from a small handful of model systems. Here, I evaluate host–microbe interactions and innate immunity in sponges using the highly tractable freshwater sponge, Ephydatia muelleri. I report the discovery of an external host-derived matrix …

Antimicrobial Responses Of Staphylococcus Aureus In Simulated Spaceflight Conditions, Mikayla Dutkiewicz, Yegor Bushnev

Discovery Day - Daytona Beach

Microbial persistence in confined environments, such as spacecraft, can pose challenges to astronaut health and habitat maintenance. This project investigates Staphylococcus aureus, a Gram-positive bacterium commonly associated with human microbiota and opportunistic infections, in spaceflight-relevant environmental conditions. Further, this project will assess the influence of the antimicrobial/antioxidant compound quercetin to assess its effects on bacterial growth and virulence under standard Earth gravity and simulated International Space Station (ISS) conditions. This approach will assess whether spaceflight-relevant stressors, including microgravity and radiation, alter treatment efficacy by influencing microbial physiology and antimicrobial susceptibility. Data collection and analysis are ongoing, and results are expected …

Assessing Non-Thermal Plasma In Cutaneous Regeneration, Arden Rodriguez, Meliah Martin, Graeme Grainger, Arineh Shahbazi

Discovery Day - Daytona Beach

Chronic and acute wounds remain a significant clinical challenge, particularly in austere and resource-limited environments where access to advanced care is restricted. Non-Thermal Plasma (NTP) has emerged as a promising, non-invasive modality with reported antimicrobial and regenerative properties; however, its mechanisms of action and effects on human skin tissue require further characterization. The scope of this project is to engineer and utilize a 3D human skin epithelial model to evaluate the effects of NTP on wound healing. We will first build a 3D epithelial tissue model that will simulate human skin, followed by modeling and evaluation of wound pathology and …

The Osteocyte-Osteoblast Network Requires Dynamic Mechanical Loading For Key Functions, Kevin Kowalski

Discovery Day - Daytona Beach

Spaceflight investigations have demonstrated that reduction in gravity-induced loading regimes is detrimental to maintenance Earth-normal bone and marrow. Mechanistically, however, there are still gaps in knowledge about how the reduction in gravity influences the different niches within the tissue. For example, cortical bone is a stable semi-solid structure that allows for only minor deformations before failure, while marrow is a viscous hydrogel-like material that can resist significant fluidic and compressive forces. We hypothesize that maintenance of different niches within the bone microenvironment are dependent on different loading regimes, and that the collective impact if gravity-induced loading needs to be considered …

Modulation Of Electrophysiology And Plaque Aggregation In Huntington’S Disease Patient-Derived Cells By Picosecond Pulsed Electric Fields, Mackenzie A. Tardif-Kunk

Biomedical Sciences Theses & Dissertations

Huntington’s Disease (HD) is a fatal, autosomal dominant neurodegenerative disorder characterized by progressive motor and cognitive decline. Unstable expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats in the huntingtin gene, often exceeding 35–40 repeats, results in an extended polyglutamine (PolyQ) tract in the translated protein. Abnormal folding of the mutant huntingtin (mHTT) protein leads to accumulation and aggregation within the cell, dysregulating various cellular processes through molecular sequestration. While several therapeutic strategies have been proposed, this disease remains incurable with treatments limited to symptom management.

Pulsed electric fields (PEF), primarily in the microsecond and nanosecond ranges, have been studied extensively for the …

The Rpm-1/Phr Signaling Hub Modulates Tau-Induced Neurodegeneration Through Regulation Of Microtubule Stability And Mapk Pathways In C. Elegans, Xinxing Ding

Theses and Dissertations

Neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia, are characterized by the accumulation of pathological tau proteins and progressive neuronal loss. Although research regarding tau-mediated toxicity is extensive, the specific pathology that determine whether neurons maintain homeostasis or succumb to collapse under tau-induced stress remain incompletely elucidated. A central, yet still insufficiently understood, feature of these diseases is the disruption of the microtubule (MT) cytoskeleton . The PHR protein family is evolutionarily highly conserved; within this family, RPM-1 in C. elegans functions as an intracellular signaling hub that regulates axon development, synapse formation, axon termination, and various microtubule-associated processes. This …

Oxidative Stress Mediated Glutamate Release And Nmda Receptor-Dependent Synaptic Remodeling In Radiation-Induced Cognitive Dysfunction, Thanh Lam

Dissertations and Theses (Open Access)

In children younger than 14 years old, the brain and other parts of the central nervous system are the most common sites for solid tumors. Radiotherapy is an effective treatment for central nervous system (CNS) tumors. However, it often causes a progressive decline in cognitive functions, which is especially devastating for pediatric patients. Although post-mitotic neurons are generally considered resistant to radiation-induced immediate cell death, ionizing radiation causes complex neurochemical and structural changes that damage synaptic integrity. In this study, we examined the molecular cascades following a 10 Gy radiation dose applied to mouse cortical neurons. We found that radiation-induced …

The Impact Of Hypoxia And Androgen Inhibition On Prostate Cancer Cell Dedifferentiation And The Dna Damage Repair Response At Telomeres, Arooba Ayaz

Biomedical Sciences Theses & Dissertations

Long-term Androgen deprivation therapy (ADT) is used to treat Prostate cancer (PCa) but is often met with resistance & the development of Neuroendocrine (NE) PCa which is rarer but more aggressive. Antiandrogens are a part of ADT that work to inhibit androgen receptor in PCa cells. In vitro, PCa cells under long-term antiandrogen treatment become NE-like and adopt stem-like characteristics. The disruption of androgen signaling though the use of antiandrogens impacts many cellular processes that play a major role in cancer cell proliferation such as the DNA damage repair response (DDR) and telomere dysfunction. In vivo, PCa tumors have disorganized …

Homocysteine Thiolactone From Translation Proofreading Is An Endogenous Ligand For Cell-Cell Signaling By The Receptor Sdia, Lorenzo Eugenio Leiva, Roberto A. Zúñiga, Gregory J. Phillips, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Several widespread mechanisms enable cellular communication and coordinate the behavior of bacterial populations. The modules responsible for cellular communication are often found in matching pairs: an enzyme that synthesizes a signal molecule and a specific receptor that decodes it. A notable exception is Escherichia coli SdiA, a homolog of known N-acyl-homoserine lactone (AHL) receptors, for which no corresponding AHL synthase exists. SdiA is an orphan receptor that enables cross-talk by sensing AHLs from other bacterial species. In this work, we investigated whether homocysteine thiolactone (HTL), an AHL-like molecule arising from a proofreading reaction of methionyl tRNA synthetase (MetRS) to correct …

Exploring Staphylococcus Aureus Host-Pathogen Interaction Using Proteomic Technologies, Emilee Marlene Elizabeth Mustor

USF Tampa Graduate Theses and Dissertations

Staphylococcus aureus deploys an arsenal of virulence effectors to remodel the host environment during infection, while simultaneously the host mounts an immune response to contain and eliminate this bacterium. This dynamic interplay defines the host-pathogen interface and shapes infection outcome. In this context, the secreted proteases represent a major arm of S. aureus pathogenesis, promoting bacterial persistence in the host by dismantling immune defenses, cleaving host signaling molecules and reshaping the host proteome. However, traditional substrate-by-substrate characterization cannot reveal the full scope of proteolytic activity occurring during infection. To address this, we developed Terminal Amine-Guanidination of Substrates-Charge Reversal (TAGS-CR), a …

Antioxidant Potential Of A Non-Heme Iron Complex: Mitigating H2O2-Induced Cellular Damage, Magy A. Mekhail, David M. Freire, Cameron Bowers, Grant Elam, Nora Del Bosque, Hannah K. Pyle, Sarah K. Dunn, Spencer Lanyon, Timothy J. Hubin, Giridhar Akkaraju, Kayla N. Green

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Iron complexes with antioxidant activity have garnered significant interest for both general and medical applications, yet few studies have yielded functional nonheme iron-based mimics for H₂O₂ mitigation in aqueous environments. Here, we investigate water-soluble nonheme iron complexes derived from 12-membered pyridinophanes (^CF₃PyN₃, PyN₃, ^NMe₂PyN₃, and Py₂N₂) to evaluate the impact of ligand scaffolds on H₂O₂ decomposition activity both in vitro and in a cellular model. Speciation and kinetic analyses reveal that both electronic and geometric modulation of the macrocyclic …

A Computational Micropatterning Approach To Study Caveolae And Protein Localization In Vascular Biology, Andrew B. Grespin

Electronic Theses and Dissertations

Caveolae are specialized, flask-shaped membrane invaginations highly expressed in endothelium and dysregulated in atherosclerosis. Caveolae play a central role in buffering membrane tension, yet the principles governing their spatial organization remain elusive. Thus, we sought to generate the most comprehensive and systematic analysis of blood vessel caveolar spatial organization. However, cell culturing, the backbone of human-focused biological research, does not standardly do well to model physiologically relevant cell behaviors such as migration or polarity-based tissue formation, particularly for punctate proteins and structures like caveolae. Micropatterns are cell-adhesive shapes that biophysically confine cell(s) to a user defined geometry which stereotype organelle …

Structure-Based Discovery Of Malate Dehydrogenase Inhibitors With Efficacy Against C. Parvum Oocysts, Ankita Bharatbhai Kheni

Biochemistry and Molecular Biology

Cryptosporidium parvum, the etiological agent of Cryptosporidiosis (diarrheal illness) represents a significant global health burden, particularly affecting immunodeficient and pediatric populations. Since the parasite has a highly reduced mitochondrion and relies on glycolysis, enzymes such as C. parvum malate dehydrogenase (CpMDH), which are believed to be indispensable for parasite viability due to their pivotal roles in NAD⁺ regeneration and redox balance, remain largely unexplored as therapeutic targets. The present study employed a multifaceted experimental and computational strategy to evaluate the inhibitory activity of two lead-like and drug-like small molecules, referred to as compound 1.8 and compound 1.5, against the cofactor …

Sleep-Circadian Modulation Of Autophagy And Glymphatic Function: Failure Of Coordinated Brain Clearance In Parkinson's Disease, Shamaila Zafar, Jay S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Parkinson's disease (PD) involves α-synuclein accumulation and progressive neurodegeneration. This review proposes that PD reflects failure of sleep-circadian regulated brain clearance network integrating intracellular autophagy and extracellular glymphatic transport across neurons, glia, and blood-brain-barrier. Disruption of sleep-architecture and circadian-timing desynchronizes these processes, impairing protein clearance and promoting pathology. This framework positions sleep-circadian dysfunction as an upstream mechanism, suggesting that restoring sleep-circadian regulation may improve protein clearance and support disease-modifying strategies.

Loss Of Mct1 Mediated Lactate Uptake Causes Delayed Endplate Maturation And Intervertebral Disc Degeneration, Maria Tsingas, Konstantinos Tsingas, Mei Smyers, Wujuan Zhang, Aaron R. Goldman, Eulisa Lawrence, John A. Collins, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

During skeletal growth, it is thought that the lactate secreted by the glycolytic nucleus pulposus (NP) cells exits the intervertebral disc into circulation via endplates. Our current studies challenge this long-held notion. Mice with early postnatal, endplate, and annulus fibrosus-specific deletion of lactate importer, MCT1, exhibited disc degeneration characterized by NP cell loss and pronounced endplate structural changes. Using metabolic and transcriptomic approaches, we demonstrate that MCT1 loss inhibits endplate chondrocyte differentiation and that lactate serves both as a crucial TCA metabolite and promotes protein and histone lactylation and gene expression. These findings suggest that during skeletal growth, NP-derived lactate …

The Impact Of Tgfβ Conditioning And Socs3 Expression On Cytokine Signal Transduction And Inflammatory Gene Expression In Fibroblasts, Morgan Anderson-Crannage

NYMC Student Theses and Dissertations

Inflammation is a major driver in many aspects of recessive dystrophic epidermolysis bullosa (RDEB) pathology, including impaired wound healing, fibrosis, and potentially cutaneous squamous cell carcinoma development. Fibroblasts, as key stromal cells in the dermis, are responsible for orchestrating inflammatory responses through the secretion of cytokines and chemokines upon stimulation with IL-1α or IL-6. Suppressor of Cytokine Signaling 3 (SOCS3) functions as a negative feedback regulator of cytokine signaling and has emerged as a key modulator of inflammatory responses in immune cells and fibroblasts. Transforming Growth Factor Beta (TGFβ), a known driver of fibrosis in RDEB, has been implicated in …

In Vitro Reversal Of Abc Transporter Mediated Multidrug Resistance In Human Ovarian And Non-Small Cell Lung Cancer Models, Alison K. Kellom, Pia D. Vogel

Biological Sciences Theses and Dissertations

One of the major causes of treatment failure in aggressive cancers is multidrug resistance (MDR), which is linked to the overexpression of membrane efflux proteins that export chemotherapeutics from cancer cells. This mechanism prevents chemotherapeutic drugs from reaching cytotoxic concentrations intracellularly, allowing the cancer to survive. Two primary mediators of this mechanism are P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). P-gp and BCRP are transmembrane ATP-binding cassette (ABC) transporters that are frequently overexpressed in MDR cancers. They utilize the binding and hydrolysis of ATP to transport a diverse range of amphipathic molecules of varying size (Schinkel and Jonker, 2003), …

Mllt1 Is Required To Maintain B-Lymphopoiesis, Janani Prakash

Dissertations

MLLT1 (also named ENL) is an epigenetic reader protein that binds to crotonylated or acetylated lysine residues of histone 3 through its N-terminal YEATS domain. Positive and negative regulatory complexes compete for binding to C-terminal MLLT1, and promote transcription elongation (SEC, Super elongation complex; DOT1L) or transcriptional repression (PRC1, Polycomb repressive complex 1). MLLT1 was initially identified as a chromosomal translocation partner to MLL(KMT2A) in a subset of MLL-rearranged leukemias. MLL-ENL fusion protein causes both lymphoid (predominantly B-ALL) and mixed lineage leukemias. MLLT1 has been implicated in leukemic stem cell survival in MLL-rearranged cell lines but its role in normal …

Junctional Actin As A Mechanical Hub For Supracellular Actomyosin Force Transmission During Apical Constriction, Jasneet Brar

UNLV Theses, Dissertations, Professional Papers, and Capstones

Apical constriction is a conserved morphogenetic mechanism that drives epithelial folding during development. During ventral furrow formation in Drosophila melanogaster, contractile actomyosin networks generate forces that reduce apical cell area resulting in tissue invagination. For these cell-scale forces to produce coordinated tissue-scale changes, contractile networks must be mechanically integrated across neighboring cells. Although adherens junctions are known to mediate this coupling, it is unclear how junctions are integrated into cortical actin cytoskeleton, which directly determines cell, and consequently tissue, shape. This thesis tests the hypothesis that supracellular actomyosin organization during apical constriction depends on distinct adherens junction based mechanical couplings: …

Potential Innate And Adaptive Roles Played By Γδ T Cells In A Bacterial Immunization Model, Lee Anne Talbot

Seton Hall University Dissertations and Theses (ETDs)

Francisella tularensis is a highly infectious intracellular bacterium and the causative agent of tularemia, with pulmonary infection resulting in severe disease and high mortality if untreated. While protective immunity to F. tularensis has been largely attributed to CD4⁺ T cell–mediated IFN-γ responses, the contribution of γδ T cells to mucosal immunity and vaccine-induced protection remains poorly defined. The objective of this study was to characterize the role of γδ T cells during primary pulmonary infection with F. tularensis live vaccine strain (LVS) and following intranasal immunization with inactivated F. tularensis (iFt) prior to LVS challenge.

Using a murine intranasal infection …

Thrombin-Induced Myofibroblast Differentiation Is Regulated By Myocardin And Novel Effector Genes In Ipf Fibroblasts, Christiana Okeke

Biotechnology Theses

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by fibroblast activation, excessive extracellular matrix (ECM) deposition, and irreversible respiratory decline. In this study, we investigated the role of myocardin and its downstream effectors, RGS5, DLGAP5, and TAGLN, in thrombin-induced myofibroblast differentiation and ECM remodeling using primary human IPF fibroblasts. Myocardin knockdown significantly attenuated thrombin-induced expression of profibrotic genes, including FN1, COL1A1, PAI-1, ACTA2, and CNN1, as well as the novel effectors RGS5, DLGAP5, and TAGLN, confirming myocardin as a central regulator of fibrotic signaling. Silencing RGS5 produced minimal effects on gene and protein expression despite minor downward …

The Dynamics Of Synchrony On Replicating Biological Populations, Montse Torres Garcia, Kevin Mcgoff, Francis Motta, Breschine Cummins, Steve Haase

Biology and Medicine Through Mathematics Conference

No abstract provided.

Cell Cycle Inhibition: Illudin S And Its Effects On Cdk2 In Ewing Sarcoma, Stephanie Diez, Natalie Flores, Alexandria Hernandez, Viviana Palacios, Terry Jo Shackleford

Cell and Molecular Methods

Ewing Sarcomas are aggressive round cell mesenchymal neoplasmas that have a high occurrence in children and young adults. CDK2 is a protein that is involved in the G1 phase of the cell cycle, which promotes the transition to the S phase. CDK2 kinase activation is mainly observed in the G1/S-phase transition.3 CDK2 binds to Cyclin proteins is responsible for entry and progression, thereby leading to maximal apoptosis activity in the S-phase. Illudin S is a drug that has been known to target cancer-specific cells, such as leukemia. Illudin S, in general are a cytotoxic metabolite that comes from plants, specifically …

Yap1 Knockdown And Panobinostat Treatment Increase Apoptotic Response And Decrease Gene Expression In Ewing Sarcoma Cells, Luna Collazo-Garcia, Alejandra Favela Santos, Madeline Torres-Salazar, Isabella Toscano, Terry Jo Shackleford

Cell and Molecular Methods

Ewing sarcoma (EWS) is considered to be one of the most aggressive pediatric malignancies, often characterized by its dysregulated gene expression driven by oncogenic fusion proteins. The Hippo signaling effector Yes-associated protein 1 (YAP1) has been known in promoting cell proliferation, survival, and therapeutic resistance in multiple cancers. However, its role in Ewing sarcoma response to treatment remains unclear. This study investigated whether YAP1 knockdown enhances the sensitivity of Ewing sarcoma cells to the histone deacetylase inhibitor Panobinostat. Ewing sarcoma, ES8, cells were transfected with a YAP1-targeting siRNA (siYAP1) or a non-targeting control (siControl) and treated with DMSO, 0.1 μM, …