Cell Biology Commons^™

Investigating The Potential Ability Of The Tlr4-Nf-Κb Axis To Reduce Aryl Hydrocarbon Receptor Expression In Intestinal Epithelial Cells, Gabriella Longoria

Student Scholar Symposium

Necrotizing enterocolitis (NEC) primarily affects premature infants and is characterized by intestinal necrosis, inflammation, and high mortality. Toll-like receptor 4 (TLR4)-induced apoptosis of intestinal epithelial cells is thought to drive NEC development. Upon binding bacterial lipopolysaccharide (LPS), TLR4 signaling activates NF-κB, leading to inflammatory gene expression. Indole-3-carbinol (I3C), a pro-ligand of the aryl hydrocarbon receptor (AhR), prevents NEC in a mouse model by downregulating TLR4, despite reduced AhR expression in NEC-affected intestines. However, the molecular mechanism behind the reduced expression of AhR in NEC is unclear. To model NEC in vitro, we treated IEC-6 enterocytes with LPS, which reduces AhR …

Functionality Of The Ryanodine Receptor Type 1 (Ryr1) In The Development Of Malignant Hyperthermia (Mh), Cesar Medina, Joshua Owens

Student Scholar Symposium

Malignant Hyperthermia (MH) is a rare but potentially lethal pharmacogenetic disorder, affecting roughly 1 in 30,000 children and 1 in 100,000 adults undergoing surgery. MH can be triggered by agents used for general anesthesia. These may include volatile anesthetics such as sevoflurane, isoflurane, desflurane, halothane or depolarizing neuromuscular blockers such as succinylcholine. Upon administration of a trigger, an MH susceptible (MHS) patient can develop a hypermetabolic state during the intraoperative or postoperative periods. If not treated quickly, an MH episode could result in organ dysfunction or death. The primary mechanisms involved in the development of an MH crisis include the …

Microrna-Mediated Regulation Of The Parkinson's Disease-Associated Gene, Lrrk2, Peyton B. Hanser, Pavithra Madamarandawala, Wendy Olivas

Undergraduate Research Symposium

Parkinson’s Disease (PD) is an age-related neurodegenerative disease. LRRK2 is one of the main PD-associated genes, as both familial mutations and its abnormal overexpression are associated with PD progression. However, underlying molecular mechanisms leading to LRRK2 abnormal overexpression are not well understood. MicroRNAs (miRNAs) are a group of small non-coding RNAs that regulate target messenger RNAs (mRNAs) by binding to a specific sequence in their 3’ UTRs (untranslated regions at the ends of mRNAs) and blocking translation of the mRNA. Previous studies have identified miR-205 as one regulator of LRRK2. However, the LRRK2 3’ UTR has many other computationally-predicted miRNA …

The Cytotoxicity And Anti-Inflammatory Properties Of 1’S-1’-Acetoxychavicol Acetate (Aca) On Oral Cells, Nur Umairah Atiqah Sabri, Nor Syazwani Muhammad Zahidan, Zulfahmi Said, Siti Noor Adnalizawati Adnan, Normaliza Ab Malik

Journal of Dentistry Indonesia

Objective: Mouthwash is widely used to maintain oral health by reducing the prevalence of pathogenic microbiomes. Nonetheless, chlorhexidine, a common active ingredient, is associated with side effects including teeth staining, mucosal peeling, mouth and tongue numbness. This has prompted interest in natural alternatives. This study aimed to identify the cytotoxicity and anti-inflammatory properties of 1’S-1’-acetoxychavicol acetate (ACA) isolated from Alpinia conchigera rhizome against human primary gingival fibroblast and keratinocyte (HPGF and HPGK). Methods: Cytotoxicity of ACA (1.57 mg/mL) against HPGF and HPGK was assessed using the MTT assay. Meanwhile, the anti-inflammatory property of ACA was analyzed based on …

Role Of Cellular Stress Responses In Innate Immune Defense Against Acute Respiratory Infections, Amit Sharma

LSU Doctoral Dissertations

The endoplasmic reticulum (ER) stress sensor inositol-requiring enzyme 1α (IRE1α) is an important regulator of innate immune cells. However, its role in pulmonary innate host defenses remains poorly understood. This dissertation elucidates the dual, context-dependent role of IRE1α in host defense against methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. We demonstrate IRE1α’s function as both a detrimental mediator of acute pathology and an essential facilitator of innate immune memory. Our work revealed that acute IRE1α activation during primary MRSA infection is detrimental. In lungs and alveolar macrophages (AMs), IRE1α is activated in response to MRSA infection. Consequently, IRE1α activation triggers a hyperinflammatory …

Evaluating The Sna1 Gene Using Crispr Mediated Knockdown In Ewing Sarcoma Cells, Rosanna Jees, Sonia Cerrillo, Terry Jo Shackleford

Mechanisms of Disease

Ewing sarcoma is a pediatric cancer with limited therapeutic options and poor long-term survival. CRISPR–Cas9–mediated gene editing provides a powerful tool for investigating tumor molecular behavior and identifying potential therapeutic targets. In this study, we worked with CRISPR–Cas9 in Ewing sarcoma ES8 cells to evaluate the roles of the transcription factors SNAI1 and SNAI2, both implicated in epithelial–mesenchymal transition and cancer progression. Using guide RNAs targeting each gene, we assessed proliferation, apoptosis, migration, and long-term survival through Incucyte live-cell imaging and colony-formation assays. Knockout of SNAI1 resulted in decreased cell proliferation and reduced migratory capacity compared with controls, suggesting a …

Δ-Valerobetaine As A Novel Inhibitor Of Breast Cancer Cell Migration: Hinders Cellular Migration Of Mcf-7 Cells Through Reducing Atp Concentrations And Fak Activation, Braxton Ivie, Lincoln Brown, Bryson Lovorn

Student Scholar Symposium

δ-valerobetaine as a Novel Inhibitor of Breast Cancer Cell Migration: Hinders Cellular Migration of MCF-7 Cells Through Reducing ATP Concentrations and FAK Activation

Lincoln Brown, Braxton Ivie, Bryson Lovorn, Joshua Owens

Based on female breast cancer diagnoses from 2014-2020, the CDC reports that the 5-year relative survival rate for local and regional breast cancers was 98.9% and 86.3%, respectively, while the survival rate for metastasized cancers was reportedly 32.4%. These discrepancies in survival highlight an increased mortality rate when cancer metastasizes. Interestingly, aggressive tumors have been shown to metabolize fats at higher rates than low-metastatic tumors. Recently, our group has …

Increased Intermembrane Space [Ca2+] Drives Mitochondrial Structural Damage In Cpvt, Shanna Hamilton, Radmila Terentyeva, Roland Veress, Fruzsina Perger, Zuzana Nichtova, Mark Bannister, Jinxi Wang, Sage Quiggle, Rachel Battershell, Matthew Gorr, Sandor Györke, Bum-Rak Choi, Christopher George, Andriy Belevych, György Csordás, Dmitry Terentyev

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Mitochondrial dysfunction caused by abnormally high RyR2 (ryanodine receptor) activity is a common finding in cardiovascular diseases. Mechanisms linking RyR2 gain of function with mitochondrial remodeling remain elusive. We hypothesized that RyR2 hyperactivity in cardiac disease increases [Ca 2+ ] in the mitochondrial intermembrane space (IMS) and activates the Ca 2+ -sensitive protease calpain, driving remodeling of mitochondrial cristae architecture through cleavage of structural protein OPA1 (optic atrophy protein 1).

METHODS: We generated a highly arrhythmogenic rat model of catecholaminergic polymorphic ventricular tachycardia, induced by RyR2 gain-of-function mutation S2236L(Ser2336Leu)(+/-) . We created a new biosensor to measure IMS-[Ca2+ ] …

Protein-Protein Interaction–Interfering Peptide Rescues Dysregulated Nmda Receptor Signaling, Robert E. Featherstone, Hongbin Li, Ameet S. Sengar, Karin E. Borgmann-Winter, Olya Melnychenko, Lindsey M. Crown, Ray L. Gifford, Felix Amirfathi, Anamika Banerjee, Aivi Tran, Krishna Parekh, Margaret Heller, Wenyu Zhang, Robert J. Gallop, Adam D. Marc, Pragya Komal, Michael W. Salter, Steven J. Siegel, Chang-Gyu Hahn

Farber Institute for Neuroscience Faculty Papers

The complex and heterogeneous genetic architecture of neuropsychiatric illnesses compels us to look beyond individual risk genes for therapeutic strategies and target the interactive dynamics and convergence of their protein products. A mechanistic substrate for convergence of synaptic neuropsychiatric risk genes are protein-protein interactions (PPIs) in the N-methyl-D-aspartate receptor (NMDAR) complex. NMDAR hypofunction in schizophrenia is associated with hypoactivity of Src kinase, resulting from convergent alterations in PPIs of Src with its partners. Of these, the association of Src with PSD-95, which inhibits the activity of this kinase in the NMDAR complex, is known to be increased in schizophrenia. Here, …

A Molecular Mechanism Of Epithelial To Mesenchymal Transition (Emt): An Evidence Based Lesson Applying Molecular Biology Through The Lens Of Cancer, Sophie Hasson, Melissa Rowland-Goldsmith

Open Educational Resources

This lesson aims to strengthen students’ critical thinking and molecular biology data analysis skills as well as their understanding of concepts related to the hallmark of cancer: tissue invasion and metastasis. Students begin by learning about the invasion of cancer cells, Epithelial-Mesenchymal Transition (EMT), and an important protein involved in EMT: E-cadherin. They then apply molecular biology knowledge to analyze data from multiple papers to infer the relationship between Snail and E-cadherin in different types of cancers. Next, they continue to interpret data from many papers to determine that a repressor transcription factor is present during EMT in cancer cells …

Modeling And Analysis Of Electric Signal In Neurons, Kevin J. Roberts

All Graduate Reports and Creative Projects, Fall 2023 to Present

Neurons in humans and other species transmit information by sending electric signals via axons. This process relies on the generation and propagation of action potentials—rapid changes in the membrane potential of the axon. Understanding the mechanisms of action potentials, including how they are generated and influenced by the axon geometry and material parameters, is crucial for gaining insight into neurological diseases such as Alzheimer’s and Multiple Sclerosis (diseases highly correlated to demyelination). In this work, we review and summarize mathematical models for signal transmission–including the classical Hodgkin-Huxley model, the Single Cable (SC) model, and the Double Cable (DC) model. We …

The Genetic And Environmental Determinants Of Stress Resilience Across Model Systems, Carson Len Stacy

Graduate Theses and Dissertations

Survival in fluctuating environments demands that organisms effectively anticipate and respond to future challenges. This capacity is shaped by both genetic background and environmental context. In this dissertation, I apply a population aware lens to explore how genetic diversity and environmental conditions intersect to shape stress survival. Integrating functional genomics and transcriptomics in Saccharomyces cerevisiae (brewer’s yeast) and a vertebrate (common canary) system, I dissect gene-by-environment (GE) interactions that underpin resilience. First, I move beyond a single reference genome by using a pan-genomic CRISPR knockout screen to assess osmotic stress survival across diverse S. cerevisiae isolates. This analysis reveals a …

Mitochondria-Mediated Epigenetic Transfer Between Chondrosarcoma And Wild-Type Cells, Caleb C. J. Wyckoff

Biomedical Sciences Theses & Dissertations

Glioblastoma (GB), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), cholangiocarcinoma, and chondrosarcoma (CS) cancers all contain mutations in the gene isocitrate dehydrogenase 2 (IDH2). The mutant IDH2 enzyme exhibits transformation of alpha-ketoglutarate (αKG) into the oncometabolite D-2-hydroxyglutarate (D2HG) in the mitochondria of these cancers. Mitochondrial-mediated transfer between cancer cells and recipient cells is a significant event that impacts the physiology of the receiving cell, specifically the epigenetic landscape. Previous experiments indicating increased DNA methylation in mesenchymal stem cells exposed to IDH1 or IDH2 conditioned medium underscore the potential role of D2HG to alter methylation states. Additionally, the presence of …

Characterization Of A New Domestic Feline Macrophage Cell Line To Study Molecular Mechanisms Of Feline Coronavirus, Adam Espinoza

Electronic Theses, Projects, and Dissertations

Feline Coronavirus (FCoV) is a veterinary pathogen common in domestic cats. FCoV is transmitted via the fecal-oral route, results in mild enteric symptoms, and is considered feline enteric coronavirus (FECV). During infection the virus may transition from infecting host enteric epithelial cells to infecting host macrophages, resulting in a lethal systemic disease, and the virus is now considered feline infectious peritonitis virus (FIPV). FIPV arises in an infected individual, is not shed in the feces, and is not transmitted from cat to cat. There is limited research defining the host molecular mechanisms driving FCoV lethal outcomes, with few feline cell …

Mathematical Model Of Ovarian Cancer Tumor Growth In Mice, Jessica A. Hoffman

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Micronuclei As A Marker Of Genotoxicity In An Urban Songbird., Elise Mittlestat

College of Arts & Sciences Senior Theses

A rise in industry and vehicle emissions in the last 20 years has led to an increase in exposure to air pollution. Air pollution has been identified as a major threat to both human and animal health and it has been linked to elevated oxidative stress. One of the most severe consequences of oxidative stress is genotoxic damage. Birds have been identified as promising sentinels for human health, but the effects of air pollution on genotoxicity in birds is understudied. In this study, I evaluated the association between air pollution and markers of genotoxicity in American Robins (Turdus migratorius) to …

Analysis Of Mct-1 Expression In Mouse Neural Retina In Response To Chronic Inflammation, Ian W. Ronson

PANDION: The Osprey Journal of Research and Ideas

Chronic inflammation is a current public health concern as it is linked to the etiology and symptoms of numerous diseases, for example diabetic retinopathy (DR). In the case of DR, inflammation leads to dysregulation of the blood retina barrier causing retinal hemorrhage and macular edema leading ultimately to irreversible vision loss. MCT-1 is critical for the survival of photoreceptor cells because MCT-1 forms protein complexes with Basigin, a cell-cell adhesion protein, that enables Müller glial cells to efficiently provide lactate as a high energy fuel source. Previous studies have shown chronic inflammation reduces Basigin expression in the retina and that …

Alphasperm Data, Seth J. Parks, Timothy G. Jenkins

ScholarsArchive Data

Data from a prospective cohort study of sperm DNA methylation, semen analysis, and DNA fragmentation in fertile and infertile men before and after treatment with a male fertility antioxidant supplement.

K847a Mutation And Anionic Lipid-Presence Modify Opa1 Enzyme Kinetics And Function, J. Rafael Tolentino, Kate Walsh, Andrew D. Kehr

Annual Student Research Poster Session

Opa1 is a dynamin superfamily protein that is responsible for the fusion of the mitochondrial membrane. However, nobody knows the specific chemical mechanisms of how it interacts with lipids. Our research focuses on investigating how Opa1 interacts with lipids. In other words, we want to figure out which amino acids are crucial for Opa1's ability to bind with lipids. In hopes of understanding how Opa1 mutations affect neurodegenerative diseases, such as dominant optic atrophy.

Er Stress Tolerance Is Regulated By Copper-Dependent Perk Kinase Activity., Sarah E. Bond Newton, Xinglong Shi, Noah R. Beratan, Julia Perhacs, Jitendra K. Arya, Margaret K. Bond, Tali Gidalevitz, Cagla Akay-Espinoza, Donita C. Brady, Kelly L. Jordan-Sciutto

Farber Institute for Neuroscience Faculty Papers

Pancreatic/PKR-like endoplasmic reticulum (ER) kinase (PERK) is a kinase that, in response to ER stress, mediates dual homeostatic and pro-apoptotic signaling. Thus, intricate regulation is required for physiological function. Attempts to modulate PERK activity have shown that the determinants of adaptive vs. maladaptive signaling remain ambiguous. Here, with purified protein, we provide evidence that PERK binds copper, identifies residues required for interaction, and demonstrates that copper is necessary for kinase activity. Furthermore, cellular PERK activity can be modulated via copper availability, and this regulatory relationship can be manipulated to dictate ER stress tolerance. Critically, these phenomena translate to phenotypes in …