Cell Biology Commons^™

Simvastatin Induces Autophaghy-Mediated Cell Death In Metastatic Breast Cancer Cells, Jessica Allagoa

Theses (2016-Present)

Breast cancer remains one of the leading causes of cancer deaths among women. Due to the limited effectiveness of current anticancer drugs, ongoing research has extended towards alternative drug categories for potential treatments. Recent findings indicate that statins possess the ability to suppress tumors across various cell types. Traditionally, statins are known as a class of cholesterol-lowering agents and function by inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, a key enzyme in the mevalonate pathway. However, statins can also suppress cell proliferation and ultimately lead to cell death, which includes Type I apoptosis-induced cell death or Type II autophagy-induced cell death. Autophagy is …

Foxo1 Inhibitor, As1842856, Induces Cell Cycle Arrest And Reverses Anticancer Drug-Induced Cytotoxicity In Osteosarcoma Cells, Antanay Hall

Theses (2016-Present)

Forkhead box class O (FOXO)-1 transcription factor controls cell proliferation, apoptosis, oxidative stress, and other cellular activities; FOXO1 has also been implicated in cell cycle regulation. This research project aims to determine the contribution of FOXO1 to cell cycle regulation and response to anticancer drug treatment in osteosarcoma. Osteosarcoma is the most common bone cancer, with most cases occurring in people younger than 30 years old. The study explores the impact of FOXO1 inhibitor AS1842856 on the cytotoxic effects of anticancer drugs in CCHOSD, Hos, and LM7 osteosarcoma (OGS) cell lines. Following chemical inhibition of FOXO1 and anticancer drug treatment, …

Loss Of Tumor Suppressor Tmem127 Drives Ret-Mediated Transformation Through Disrupted Membrane Dynamics, Timothy J Walker, Eduardo Reyes-Alvarez, Brandy D Hyndman, Michael G Sugiyama, Larissa C B Oliveira, Aisha N Rekab, Mathieu J F Crupi, Rebecca Cabral-Dias, Qianjin Guo, Patricia L M Dahia, Douglas S Richardson, Costin N Antonescu, Lois M Mulligan

Faculty, Staff and Student Publications

Internalization from the cell membrane and endosomal trafficking of receptor tyrosine kinases (RTKs) are important regulators of signaling in normal cells that can frequently be disrupted in cancer. The adrenal tumor pheochromocytoma (PCC) can be caused by activating mutations of the rearranged during transfection (RET) receptor tyrosine kinase, or inactivation of TMEM127, a transmembrane tumor suppressor implicated in trafficking of endosomal cargos. However, the role of aberrant receptor trafficking in PCC is not well understood. Here, we show that loss of TMEM127 causes wildtype RET protein accumulation on the cell surface, where increased receptor density facilitates constitutive ligand-independent activity and …

Development Of Vasculature Patterns In A Mouse Model Of Supratentorial Ependymoma, Jackson Ayers

Honors Scholar Theses

Supratentorial Ependymoma (ST-EPN) is a subtype of ependymoma, a primary solid tumor found throughout the nervous system. ST-EPN are most commonly caused by an oncogenic fusion between the zinc finger gene ZFTA and the RELA, and this distinct ependymoma subtype is readily modeled in mice by conditional expression of ZFTA-RELA in radial glial cells. ST-EPN are known to have a distinctive arrangement of tumor cells and vasculature forming pseudo-rosettes in which polarized tumor cells surround blood vessels within the tumors. It is not known how these pseudo-rosettes or the tumor vasculature form and develop in ST-EPN, so in this study …

Ammonium Chemotaxis In Chlamydomonas Reinhardtii, Gabela Nelson

LSU Doctoral Dissertations

Analysis of ammonium chemotaxis in Chlamydomonas reinhardtii is largely hindered, compared to that of phototaxis, despite equal importance on flagellated microalgal physiology. A major contribution of this shortfall is the lack of proper assay method. We developed a simple Petri dish assay method in which light is homogenously exposed while patterns of the cellular migration are tracked with a function of time. Using the method, new findings were revealed. First, this research presented that a strain lacking the eyespot organelle required for light gradient-sensing exhibits similar chemotactic behavior compared to a wild-type strain, suggesting Chlamydomonas sense an ammonium gradient not …

Upregulation Of The Predominant Cystic Fibrosis Causing Mutation Df508-Cftr By Triazole Compounds In Epithelial Cells, Maggie Taylor

Undergraduate Research Conference

Cystic fibrosis is a common genetic disease that is caused by a mutation in the plasma membrane protein CFTR, which stands for Cystic Fibrosis Transmembrane-conductance Regulator. When this membrane protein is mutated, it impairs its chloride ion channel function, blocking the movement of chloride ions that travel in and out of the cell. Previous studies have demonstrated that the most prevalent CFTR mutation, ∆F508-CFTR, can be partially reversed using small molecules (Heda and Marino, BBRC, 271:659-664, 2000). In this study, I have investigated the effects of several triazole compounds known to bind and transport chloride ions in cultured cells, on …

Hgs-3 The Influence Of A Tandem Cycling Program In The Community On Physical And Functional Health, Therapeutic Bonds, And Quality Of Life For Individuals And Care Partners Coping With Parkinson’S Disease, Leila Djerdjour, Jennifer L. Trilk

SC Upstate Research Symposium

Purpose Statement: Several studies have shown that aerobic exercise can have a positive impact on alleviating symptoms experienced by individuals with Parkinson's disease (PD). Despite this evidence, the potential benefits of exercise for both PD patients and their care partners (PD dyad) remain unexplored. This research project investigates the effectiveness, therapeutic collaborations, and physical outcomes of a virtual reality (VR) tandem cycling program specifically designed for PD dyads.

Methods: Following approval from the Prisma Health Institutional Review Board, individuals with PD were identified and screened by clinical neurologists. The pre-testing measures for PD dyads (N=9) included emotional and cognitive status …

Role Of Centrosomal P4.1 Associated Protein (Cpap) In Tumor Suppression, Heena Dave

MUSC Theses and Dissertations

In eukaryotic cells, centrosomes are membrane-less organelles that function as the primary microtubules organizing center with a crucial role in cell division. For accurate bipolar spindle assembly and genetic transmission between generations, fidelity in centriolar duplication is critical. Disruption in this process can cause genomic instability, which could then lead to conditions like aneuploidy, a common feature of various cancers. Among the numerous proteins associated with mammalian centrioles, the centrosomal P4.1 associated protein (CPAP) stands out for its essential role in regulating centriole duplication. Dysfunctions in CPAP have been linked to abnormalities in centriole length that can contribute to conditions …

Role Of Protein Kinase A And A Kinase Anchoring Proteins In Buffering And Compartmentation Of Camp Signalling In Human Airway Smooth Muscle Cells, Rinzhin T. Sherpa, Karni S. Moshal, Shailesh R. Agarwal, Rennolds S. Ostrom, Robert D. Harvey

Pharmacy Faculty Articles and Research

Background and Purpose

In human airway smooth muscle (hASM) cells, not all receptors stimulating cAMP production elicit the same effects. This can only be explained if cAMP movement throughout the cell is restricted, yet the mechanisms involved are not fully understood. Phosphodiesterases (PDEs) contribute to compartmentation of many cAMP responses, but PDE activity alone is predicted to be insufficient if cAMP is otherwise freely diffusible. We tested the hypothesis that buffering of cAMP by protein kinase A (PKA) associated with A kinase anchoring proteins (AKAPs) slows cAMP diffusion and that this contributes to receptor-mediated, compartmentalized responses.

Experimental Approach

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The Plant Disease Triangle Facing Climate Change: A Molecular Perspective, Charles Roussin-Léveillée, Christina A. M. Rossi, Christian Castroverde, Peter Moffett

Biology Faculty Publications

No abstract provided.

Pulsed Electric Fields Sensitize Methicillin-Resistant Staphylococcus Aureus To Antibacterial Therapies And Stimulate Host Immune Responses, Alexandra E. Chittams-Miles

Biomedical Sciences Theses & Dissertations

This research explores the impact of nanosecond pulsed electric fields (nsPEF) on two fronts: their immune stimulatory effects and their potential as a novel strategy to enhance the sensitivity of Methicillin-resistant Staphylococcus aureus (MRSA) to clinically relevant antibiotics. While pulsed electric fields have been reported to have an immune stimulatory effect, the mechanisms responsible for these effects have yet to be determined.

Our investigation addresses the rising concern of MRSA derived skin and soft tissue infections (SSTIs). Consistent with other publications, we found that nsPEF alone cause modest inactivation of planktonic MRSA. We then investigated the effects of nsPEF in …

Autophagy And Ime2 Kinase In Regulation Of Meiotic Exit In Saccharomyces Cerevisiae, Somdutta Paul

Dartmouth College Master’s Theses

Meiosis or gametogenesis is a specialized cell division that produces gametes in sexually reproducing organisms. The process of meiosis reduces the genetic content into half that of the progenitor cell. This reduction in the genetic content occurs over a set of two divisions: meiosis I and meiosis II. Because gametes are essential for propagation of life, meiosis operates under tight regulation ensuring the full functionality and viability of the gametes produced. The working principle of the regulatory network that restricts meiosis to only two divisions is not clearly understood. Budding yeast undergoes meiosis in response to starvation. Autophagy being a …

Deciphering The Functional Connections Between The Nuclear Paraspeckle And Rad51 Homologous Recombination Proteins Using A Yeast Protein Interaction System, Eric J. Nutz

Senior Theses

Homologous recombination (HR) is a repair pathway for DNA double-stranded breaks. Mutations in HR genes contribute to genomic instability and increase the prevalence of cancer. Exploiting HR deficiency in tumor cells has led to improved synthetic lethality outcomes. RAD51 paralogue protein complexes are known to be involved with HR. Proteomic analysis of RAD51 paralogues reveals a connection to the nuclear paraspeckle. A paraspeckle is a little-known, specialized organelle found in the interchromatin space of the nucleus in mammalian cells. Its three central protein components include SFPQ, NONO, and PSPC1. RAD51D is an HR protein shown previously to interact with SFPQ …

Formation Of New Cohesive Linkages And Regulation Of Cohesion Rejuvenation During Meiotic Prophase In Drosophila Oocytes, Muhammad Abdul Haseeb

Dartmouth College Ph.D Dissertations

During meiosis, faithful segregation of chromosomes requires maintenance of sister chromatid cohesion from premeiotic S phase until its stepwise dissolution at anaphase I and anaphase II. Research in humans and model organisms indicates that premature loss of meiotic cohesion is a major determinant of age-induced aneuploidy in human oocytes, a phenomenon known as the maternal age effect. Because cohesin turnover after S phase has not been detected in mice oocytes, the prevailing model for mammalian oocytes is that cohesion cannot be replenished after its initial establishment in S phase. However, previous research from the Bickel lab suggested that a cohesion …

In Silico Analysis Of C-Type Lectins As Co-Infection Receptors Of Dengue And Chikungunya Viruses In Aedes Aegypti, Munawir Sazali, R. C. Hidayat Soesilohadi, Nastiti Wijayanti, Tri Wibawa, Arif Nur Muhammad Ansori

Makara Journal of Science

Aedes aegypti is a primer vector of dengue virus (DENV) and chikungunya virus (CHIKV). The susceptibility of mosquitoes to DENV and CHIKV depends on their recognition receptor of pathogens. C-type lectins (CTLs) are an important mediator of virus infection in A. aegypti. This study aims to identify potential receptors and determine the binding affinity between ligand–receptor interaction, CTLs and virus envelopes (DENV-1, 2, 3, and 4 and CHIKV) interaction based on in silico analysis. Sample sequences were obtained from GenBank (NCBI), and 10 CTLs were acquired from VectorBase. Homology modeling based on a minimum standard of 20% was processed …

Honey Targets Ribosome Biogenesis Process In Human Pancreatic Cancer Cells To Inhibit Their Growth And Metastatic Phenotypes, Aun A. Bangash, Muhammad Bangash, Haider Ahsan, Shiza Khan, Mudassier Ahmad, Dae Joon Kim, Sahir Alvi, Bilal Hafeez

Research Symposium

Background: Pancreatic cancer (PanCa) is the fourth deadliest cancer worldwide and is expected to become the second deadliest cancer by 2030. In the USA, the National Cancer Institute put forth a grim prediction stating that there will be 64,050 new cases in 2023 alone and about 50,000 of these patients will die. Existing therapeutic regimens against PanCa are not that effective and show unacceptable toxicities. Therefore, developing highly effective new agents with less toxicity is urgently required, which could be used as a monotherapy or as an adjuvant to treat PanCa patients. Honey is known for its tremendous health benefits …

Real-Time Camp Dynamics In Live Cells Using The Fluorescent Camp Difference Detector In Situ, Isabella Cattani-Cavalieri, Jordyn Margolis, Camelia Anicolaesei, Francisco J. Nuñez, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

cAMP Difference Detector In Situ (cADDis) is a novel biosensor that allows for the continuous measurement of cAMP levels in living cells. The biosensor is created from a circularly permuted fluorescent protein linked to the hinge region of Epac2. This creates a single fluorophore biosensor that displays either increased or decreased fluorescence upon binding of cAMP. The biosensor exists in red and green upward versions, as well as green downward versions, and several red and green versions targeted to subcellular locations. To illustrate the effectiveness of the biosensor, the green downward version, which decreases in fluorescence upon cAMP binding, was …

Valproic Acid Alters Larval Behavior And Neuronal Composition Within The Optic Tectum Of Zebrafish, Bailey J. Calder, Jacquelyne C. Howell, Michael J. Zeyer, Annalie Martin, Sierra C. Dixon, Shane M. Lilya, Jason M. Hansen, Arminda Suli

Library/Life Sciences Undergraduate Poster Competition 2024

The mammalian superior colliculus (SC) and its non-mammalian homolog–the optic tectum (OT)–are midbrain structures that integrate multimodal sensory inputs and guide involuntary movements in response to relevant environmental cues. Recent work has drawn strong connections between the functions of the SC/OT and behavioral deficits observed in autism spectrum disorder (ASD), thus implicating this structure as a possible site affected in ASD. Since fetal exposure to valproic acid (VPA) has been associated with increased prevalence of ASD in humans, and ASD-like phenotypes in animal models, we exposed embryonic zebrafish to VPA to investigate the connection between ASD and OT development. In …

Whole Genome Sequencing Of The Whipple Azalea Garden, Afia Asamoah, Elizabeth Toth, Amy Vasudevan, Sarah Justice, Elizabeth D. Hasenmyer

Lux et Fides: A Journal for Undergraduate Christian Scholars

Taylor University houses a large collection of North American azaleas. Deciduous azalea species, like those found on campus, are vastly understudied. This project aims to provide publicly available genomic data which will be used to study the genetic basis behind their physical characteristics and their relatedness to other species.

Mir-200c Reprograms Fibroblasts To Recapitulate The Phenotype Of Cafs In Breast Cancer Progression, Zhao Lin, Megan Roche, Víctor Díaz-Barros, Marina Domingo-Vidal, Diana Menezes, Madalina Tuluc, Guldeep Uppal, Jaime Caro, Joseph Curry, Ubaldo Martinez-Outshoorn

Kimmel Cancer Center Faculty Papers

Mesenchymal-epithelial plasticity driving cancer progression in cancer-associated fibroblasts (CAFs) is undetermined. This work identifies a subgroup of CAFs in human breast cancer exhibiting mesenchymal-to-epithelial transition (MET) or epithelial-like profile with high miR-200c expression. MiR-200c overexpression in fibroblasts is sufficient to drive breast cancer aggressiveness. Oxidative stress in the tumor microenvironment induces miR-200c by DNA demethylation. Proteomics, RNA-seq and functional analyses reveal that miR-200c is a novel positive regulator of NFκB-HIF signaling via COMMD1 downregulation and stimulates pro-tumorigenic inflammation and glycolysis. Reprogramming fibroblasts toward MET via miR-200c reduces stemness and induces a senescent phenotype. This pro-tumorigenic profile in CAFs fosters carcinoma …

A Novel Micropeptide, Slitharin, Exerts Cardioprotective Effects In Myocardial Infarction, Ahmed G. E. Ibrahim, Alessandra Ciullo, Shukuro Yamaguchi, Chang Li, Travis Antes, Xaviar Jones, Liang Li, Ramachandran Murali, Innokentiy Maslennikov, Niveda Sundararaman, Daniel Soetkamp, Eugenio Cingolani, Jennifer Van Eyk, Eduardo Marbán

Pharmacy Faculty Articles and Research

Purpose: Micropeptides are an emerging class of proteins that play critical roles in cell signaling. Here, we describe the discovery of a novel micropeptide, dubbed slitharin (Slt), in conditioned media from Cardiosphere-derived cells (CDCs), a therapeutic cardiac stromal cell type.

Experimental design: We performed mass spectrometry of peptide-enriched fractions from the conditioned media of CDCs and a therapeutically inert cell type (human dermal fibrobasts). We then evaluated the therapeutic capacity of the candidate peptide using an in vitro model of cardiomyocyte injury and a rat model of myocardial infarction.

Results: We identified a novel 24-amino acid micropeptide …

Investigating The Mechanisms Through Which Autophagy Controls Lipid Levels In Cyst Stem Cells., Jared Langdon

College of Arts & Sciences Senior Theses

With an increase in the average age of the American population, incidents of age-related diseases and illnesses are rising across healthcare communities. Addressing these pathologies with a focus towards novel treatments warrants further research into their mechanistic origins. Lipid build up within cells has been correlated with increased risk for certain pathologies, namely Alzheimer's disease and type-2 diabetes (Demarco, 2020). In this study I aimed to investigate the origin of the increase in lipids, specifically we consider the effects of lipid build up on the maintenance of stem cell populations.

Androgen Drives Melanoma Invasiveness And Metastatic Spread By Inducing Tumorigenic Fucosylation, Qian Liu

USF Tampa Graduate Theses and Dissertations

Melanoma incidence and mortality rates are historically higher for men than women, with an estimated ~47% more new cases and twice the lethality in men in the US in 2023. Consistent with these discrepancies, emerging studies have highlighted the tumorigenic role of the male sex hormone androgen and its receptor (AR) in promoting melanoma aggressiveness. However, underlying cellular and molecular mechanisms and their precise pathological contributions are not well-defined. We recently discovered a sex-associated disparity in melanoma fucosylation, the post-translational modification of proteins with the dietary sugar L-fucose. Fucosylation, the conjugation of fucose moieties onto different glycan linkages on target …

Investigating Optimal Laboratory Growth Conditions Of Gracilibacillus Halotolerans In Media Supplemented With Salt, Isaac Young

Annual Research Symposium

As interest continues to grow in the field of persister cells and their morphology, there arises an ever-evolving desire to further understand specific strains of bacteria that exemplify the qualities of seemingly anomalous survival regardless of anti-bacterial treatment. In the case of the Gracilibacillus halotolerans, a halotolerant extremophile extracted from the Great Salt Lake with known persistent characteristics, uncovering its optimal growth conditions was essential for future investigations. Identifying the optimal salinity for the growth of G. halotolerans will allow us to standardize our growth methods, uncover several mechanisms of saline tolerance, and add to future investigations of persistence with …

Ksp1 Is An Autophagic Receptor Protein For The Snx4-Assisted Autophagy Of Ssn2/Med13, Sara E Hanley, Stephen D Willis, Steven J Doyle, Randy Strich, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Ksp1 is a casein II-like kinase whose activity prevents aberrant macroautophagy/autophagy induction in nutrient-rich conditions in yeast. Here, we describe a kinase-independent role of Ksp1 as a novel autophagic receptor protein for Ssn2/Med13, a known cargo of Snx4-assisted autophagy of transcription factors. In this pathway, a subset of conserved transcriptional regulators, Ssn2/Med13, Rim15, and Msn2, are selectively targeted for vacuolar proteolysis following nitrogen starvation, assisted by the sorting nexin heterodimer Snx4-Atg20. Here we show that phagophores also engulf Ksp1 alongside its cargo for vacuolar proteolysis. Ksp1 directly associates with Atg8 following nitrogen starvation at the interface of an Atg8-family interacting …

Ras/Mapk Signaling Mediates Adipose Tissue Control Of Ovarian Germline Survival And Ovulation In Drosophila Melanogaster, Tancia Bradshaw, Chad Simmons, Rachael Ott, Alissa Richmond Armstrong

Faculty Publications

From insects to humans, oogenesis is tightly linked to nutritional input, yet little is known about how whole organism physiology matches dietary changes with oocyte development. Considering that diet-induced adipose tissue dysfunction is associated with an increased risk for fertility problems, and other obesity-associated pathophysiologies, it is critical to decipher the cellular and molecular mechanisms linking adipose nutrient sensing to remote control of the ovary and other tissues. Our previous studies in Drosophila melanogaster have shown that amino acid sensing, via the amino acid response pathway and mTOR-mediated signaling function within adipocytes to control germline stem cell maintenance and ovulation, …

Mitochondrial Quality Control By Tail-Anchored Proteins, Jose M. Delgado

Dartmouth College Ph.D Dissertations

Autophagy is a lysosome-mediated pathway responsible for the degradation of unwanted cytosolic content. During autophagy, cytoplasmic components are enveloped by a newly generated vesicle (the autophagosome), trafficked to the lysosome, and degraded. The power of autophagy lies in its ability to selectively target specific substrates for degradation—a phenomenon known as selective autophagy.

Specialized proteins known as selective autophagy receptors play a crucial role in identifying and targeting autophagy cargo. Although historically overlooked as potential regulators, our understanding of autophagy receptors is evolving beyond the assumption that receptors merely bridge targets to pre-formed autophagosomal membranes. Previous insights were often based on …

Mechanistic And Engineering Studies Of Lov Photoreceptors In Yeast, Matthew M. Cleere

Dissertations, Theses, and Capstone Projects

A variety of cellular biosensors have evolved which can translate electromagnetic radiation from the environment into biological functions. Light-Oxygen-Voltage (LOV) domains in particular, are a group of photoreceptors that respond to blue wavelengths of light and can become a cellular photoswitch by converting this stimulus through their attached effector domains. For instance, the Helix-Turn-Helix (HTH) DNA-binding activity of the bacterial transcription factor EL222 and the Regulator of G-protein Signaling (RGS) in the fungal membrane associating protein BcLOV4 are both induced by blue-light sensing LOV domains. While previous work has provided the field with a structural characterization of LOV proteins in …

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

Protein-Protein Interactions In Cell Cycle Proteins: An In Silico Investigation Of Two Important Players, Andriele Eichner

Dissertations, Theses, and Capstone Projects

The examination of the cell cycle carries significant implications for the biology, health, and overall existence of all living things. These implications span from the development and growth of these organisms to the aging process and cancer, as well as the potential of stem cell therapies to repair diseases and injuries. Numerous proteins of the cell cycle are essential for cellular division and proliferation and are widely conserved over the course of evolution. In this work, we aimed to investigate the molecular processes of protein-protein interactions in cell cycle proteins, centering on two key players: Cdc6 in budding yeast and …