Cell and Developmental Biology Commons^™

The Role Of Eor-1/Plzf In Promoting Soma Compartment Specific Death In A Non-Canonical Cell Death Program In C. Elegans, Nathan Rather

2024 Fall Honors Capstone Projects - Archive

Programmed cell death (PCD) is an essential evolutionarily- conserved and genetically encoded program for normal development and homeostasis. A previous study identified a CED-3 dependent but mechanistically non-apoptotic and highly stereotyped elimination program called Compartmentalized Cell Elimination (CCE) in the C. elegans tail-spike epithelial cell (TSC). Here the transcription factor EOR-1/PLZF is found to promote CCE. The loss of which results in a persisting non-engulfed soma with enlarged nuclei in the first larval stage. This study finds that EOR-1 and its established partners function downstream of CED-3 Caspase protease activity, a role distinct from other PCD contexts where EOR-1 has …

Quantitative Analysis Of Protective Effect Of Resveratrol Against Nanoplastic-Induced Oxidative Stress, Bryan Gustafson

All Graduate Reports and Creative Projects, Fall 2023 to Present

Nanoplastics and microplastics are a growing ecological and health concern due to their widespread prevalence. The effects of these microscopic particles in biological systems primarily relate to their potential to produce reactive oxygen species and interactive effects with other cytotoxic agents. Of particular interest in this work is the effect on mammalian intestinal cells, due to the regular unintentional ingestion of micro- and nanoplastics in the normal western diet. In this study, Caco-2 cells were cultured and exposed to polystyrene particles in vitro as a simple model of the human digestive endothelium.

Resveratrol, a naturally occurring polyphenolic compound, has been …

Differential Responses Of Human Neutrophils To Legionella Species., Hannah E. Hanford

Electronic Theses and Dissertations

Legionella species are Gram-negative facultative intracellular bacterial pathogens commonly found in freshwater or soil environments where they survive and replicate within their natural protozoan hosts. Humans serve as an accidental host for Legionella species after inhalation of contaminated aerosolized water droplets or soil particles enabling the bacteria to enter the lungs, infect alveolar macrophages, and result in severe pneumonia. Evasion of degradation and proliferation within alveolar macrophages by Legionella species and manifestation of “Legionnaires’ disease” is dependent on the Dot/Icm type IV secretion system (T4SS). The T4SS apparatus is a needle-like channel for translocation of over ~350 effector proteins, depending …

Apoa2 Increases Cholesterol Efflux Capacity To Plasma Hdl By Displacing The C-Terminus Of Resident Apoa1, Snigdha Sarkar, Jamie Morris, Youngki You, Hannah Sexmith, Scott E. Street, Stephanie M. Thibert, Isaac K. Attah, Chelsea M. Hutchinson Bunch, Irina V. Novikova, James E. Evans, Amy S. Shah, Scott M. Gordon, Jere P. Segrest, Karin E. Bornfeldt, Tomas Vaisar, Jay W. Heinecke, W. Sean Davidson, John T. Melchior

Saha Cardiovascular Research Center Faculty Publications

Abstract The ability of high-density lipoprotein (HDL) to promote cellular cholesterol efflux is a more robust predictor of cardiovascular disease protection than HDL-cholesterol levels in plasma. Previously, we found that lipidated HDL containing both apolipoprotein A-I (APOA1) and A-II (APOA2) promotes cholesterol efflux via the ATP-binding cassette transporter (ABCA1). In the current study, we directly added purified, lipid-free APOA2 to human plasma and found a dose-dependent increase in whole plasma cholesterol efflux capacity. APOA2 likewise increased the cholesterol efflux capacity of isolated HDL with the maximum effect occurring when equal masses of APOA1 and APOA2 coexisted on the particles. Follow-up …

Untargeted Lipidomics Reveals Novel Hdl Metabotypes And Lipid-Clinical Correlates, Peer W. F. Karmaus, Scott M. Gordon, Marcus Y. Chen, Alison A. Motsinger-Reif, Rodney W. Snyder, Timothy R. Fennell, Suramya Waidyanatha, Reshan A. Fernando, Alan T. Remaley, Michael B. Fessler

Saha Cardiovascular Research Center Faculty Publications

Plasma high-density lipoprotein (HDL), originally studied for its role in lipid transport, is now appreciated to have wide-ranging biological functions that become defective during disease. While >200 lipids have collectively been detected in HDL, published HDL lipidomic analyses in different diseases have commonly been targeted to prespecified subsets of lipids. Here, we report the results of untargeted lipidomic analysis of HDL isolated from 101 subjects referred for computed tomographic coronary imaging for whom multiple additional clinical and lipoprotein metadata were measured. Unsupervised clustering of the total HDL lipidome revealed that the subjects fell into one of two discrete groups, herein …

Lack Of Inflammatory Response In Mouse Embryonic Cells To Listeria Infection, Damilola Oyebode

Master's Theses

Approximately 1 in 5 pregnancies in the United States results in miscarriage, with a significant percentage of these losses attributed to failed implantation due to immunological challenges encountered by the early embryo. Recent research has shown that key cell types within mouse blastocysts, including embryonic stem cells (ESCs) and trophoblast stem cells (TSCs), exhibit remarkable resilience against the cytotoxic effects associated with viral infections and embryotoxic cytokines, such as TNFα and IFNγ, both of which are known to hinder blastocyst development. However, the immune properties of the preimplantation stage embryo, specifically the blastocyst, remain poorly understood. Using mouse cell model, …

Timigp: A Computational Framework To Determine The Tumor Immune Microenvironment Associated With Prognosis And Immunotherapy Response, Chenyang Li

Dissertations and Theses (Open Access)

Accumulating evidence has suggested that the tumor immune microenvironment (TIME) drastically impacts cancer patients’ clinical outcomes, including prognosis and immunotherapy response. However, understanding TIME remains challenging due to its complexity and heterogeneity. In this dissertation, we introduce TimiGP (Tumor Immune Microenvironment Illustration based on Gene Pairs), a computational framework designed to address this challenge. Leveraging single-cell RNA-seq (scRNA-seq) and bulk gene expression data alongside clinical information, TimiGP constructs a cell-cell interaction network that elucidates the relationship between immune cell function and relevant clinical outcomes, such as prognosis and treatment response. With immunological insights, these cell-cell interactions also facilitate the development …

The Role Of Wt1 In Müllerian Duct Development, Jace Aloway

Dissertations and Theses (Open Access)

WT1 is a zinc finger transcription factor widely expressed in the urogenital system. Human mutations of WT1 lead to pediatric nephroblastoma as well as frequent differences of sex development (DSDs). Previous studies have suggested that WT1 acts as an activator for Amhr2, a necessary component of typical male differentiation. We used the mouse as a model to investigate the role of WT1 in sex development, where we deleted Wt1 in the Müllerian duct (MD) mesenchyme using a novel conditional null reporter allele, Wt1 flox-RFP. This allele utilizes the Cre-lox system to delete exons 8 and 9 of Wt1 …

Characterizing And Targeting The Genomic Consequences Of Atrx Deficiency In Glioma, Sharvari Dharmaiah

Dissertations and Theses (Open Access)

Mutational inactivation of histone chaperone ATRX (a-thalassaemia/mental retardation X-linked) represents a defining molecular feature in several cancers, including malignant glioma. As standard of care only leads to transient responses and poor outcomes, there is an unmet clinical need for developing new therapies that target ATRX-deficient glioma. Loss of ATRX gives rise to abnormal G-quadruplex DNA secondary structures at GC-rich sites of the genome, such as telomeric and pericentromeric regions, enhancing replication stress and genomic instability. These mutations are mutually exclusive with TERT promoter mutations, promoting the alternative lengthening of telomeres (ALT) pathway as a telomere maintenance mechanism in ATRX-deficient glioma. …

Neuronal And Glial Cell Alterations Involved In The Retinal Degeneration Of The Familial Dysautonomia Optic Neuropathy, Anastasia Schultz, Henar Albertos-Arranz, Xavier Sánchez Sáez, Jamie Morgan, Diane Darland, Alejandra Gonzalez-Duarte, Horacio Kaufmann, Carlos E. Mendoza-Santiesteban, Nicolás Cuenca, Frances Lefcort

Biology Faculty Publications

Familial dysautonomia (FD) is a rare genetic neurodevelopmental and neurodegenerative disorder. In addition to the autonomic and peripheral sensory neuropathies that challenge patient survival, one of the most debilitating symptoms affecting patients' quality of life is progressive blindness resulting from the steady loss of retinal ganglion cells (RGCs).Within the FD community, there is a concerted effort to develop treatments to prevent the loss of RGCs. However, the mechanisms underlying the death of RGCs are not well understood. To study the mechanisms underlying RGC death, Pax6-cre;Elp1loxp/loxp male and female mice and postmortem retinal tissue from an FD patient were used to …

Development Of An In Vitro Squamous Metaplasia Model Using Airway Basal Stem Cells, Arash Tahmasbi

Electronic Theses, Projects, and Dissertations

Squamous metaplasia (SM) of the airway epithelium is an abnormal condition that is caused by exposure to airborne toxicants, cigarette smoke, pollutants, and pathogens. Since SM of the airway was first documented in the 1970s, data on this epithelial disease remain limited. More research is needed to fully understand this epithelial disorder and to prevent its progression into severe illnesses such as chronic bronchitis (CB), COPD, and squamous cell carcinoma. We developed 3D models of SM using airway basal stem cells (ABSCs) isolated from lung obtained from postmortem human donors. The ABSCs were cultured at the air-liquid interface (ALI) for …

A Pan-Cancer Single-Cell Analysis Of Intratumoral Copy Number Diversity And Evolution, Hanghui Ye

Dissertations and Theses (Open Access)

Aneuploidy is a hallmark of human cancers, with many copy number aberrations (CNAs) being associated with disease progression. Previous studies have revealed extensive inter-patient heterogeneity (IPH) in copy number profiles. However, the extent of intratumoral heterogeneity (ITH) and its evolutionary dynamics remain poorly understood.

To address these gaps, we developed Acoustic Cell Tagmentation (ACT), an advanced single-cell single-molecule DNA sequencing (scDNA-seq) technology, to resolve the copy number substructure of human tumors and investigate the evolution of aneuploidy. Applying ACT to eight triple-negative breast cancer (TNBC) patients to profile 9,765 aneuploid tumor cells, we discovered that following initial punctuated copy number …

The Role Of Ganglioside Gd2 And Gd3 Synthase (St8sia1) In The Regulation Of Immune Suppression In Breast Cancer, Bolutyfe Oderinde

Dissertations and Theses (Open Access)

Gangliosides are acidic glycosphingolipids involved in cell adhesion, proliferation, and modulation of signal transduction pathways. It has been reported that tumor-shed gangliosides influence the activity of immune cells including macrophages, NK cells, and T cells. GD3 synthase (GD3S) is the key enzyme that regulates the biosynthesis of the b and c series gangliosides, particularly GD3 and GD2, and studies have shown that GD3S is upregulated in most tumors and plays a role in tumor progression. Similarly, we have previously found GD3S to be significantly upregulated in GD2+ breast cancer stem cells (BCSC) compared to GD2- cells, and the knockdown of …

Assessing The Temporal Role Of Mir-200 Loss In Murine Models Of Nsclc, Jared Fradette

Dissertations and Theses (Open Access)

Lung cancer is the leading cause of cancer related deaths in the United States, with non-small cell lung cancer (NSCLC) making up a majority of new diagnoses. Metastasis is the big killer in NSCLC and is driven by epithelial-mesenchymal transition (EMT) and immune evasion. The microRNA 200 family is a master regulator of EMT and is implicated in immune regulation. In this study we have developed a novel genetically engineered mouse model (GEMM) and derived primary cell lines from them to explore the role of microRNA-200 in early EMT and immune changes. Our model combines conditional activation of Kras^{G12D …}

Functional Analysis Of The Zebrafish Orthologs Of Host Cell Factor 1 Gene, David Paz

Open Access Theses & Dissertations

Host Cell Factor C1 (HCFC1) is a transcriptional co-activator factor that regulates the expression of over 5000 different downstream target genes in human cells. Missense mutations in the HCFC1 gene cause methylmalonic acidemia homocysteinemia cblX type (cblX). cblX, a multiple congenital anomaly syndrome (MCA) characterized by abnormal brain development, craniofacial abnormalities, metabolic deficits, and intractable epilepsy. Published studies suggest that HCFC1 regulates neural precursor proliferation, number, and differentiation. However, these results were derived from studies that were performed with nonsense alleles or transient knockdown approaches. Although these results demonstrate the importance of HCFC1 in brain development, they do not replicate …

Investigation Of Chondrogenesis, Myogenesis, And Osteogenesis After 2,4-Dtbp, 2-Bp, 4-Bp, 3,5-Dtbc Exposure In Zebrafish, Haley Brashears

All Theses

Synthetic phenolic antioxidants (SPAs) are used in personal care products, food packaging, and water pipes, common SPAs include 2,4-di-tert-butylphenol (2,4-DTBP), 2-tert-butyl phenol (2-BP), and 4-tert-butyl phenol (4-BP). These compounds are detected in the environment and in human biological samples. 2,4-DTBP has been detected in cord plasma, placenta, and breast milk samples. This drives the concern regarding developmental toxicity. In human iPS cells 2,4-DTBP impairs differentiation into somites and osteoblasts. Other SPAs, like 2,6-di-tert-butyl-hydroxytoluene caused increased rates of malformations including yolk and pericardial edema, and spinal curvature in 5-day post fertilization (dpf) zebrafish. …

Integrated Transcriptomics And Proteomics Study Of Starvation Selected Drosophila Melanogaster, Aavash Adhikari

UNLV Theses, Dissertations, Professional Papers, and Capstones

Drosophila melanogaster, selected for starvation resistance exhibits phenotypic traits such as increased body size, slower development, reduced fecundity and obesity like characteristics including higher lipid reserves and cardiac dysfunction. While prior studies have explored the metabolic and biochemical changes in these flies, the underlying genetic and molecular mechanisms remain unclear. This study aims to investigate the gene expression and protein abundance in starvation-selected Drosophila through RNAseq, proteomics, and integrating both datasets using the MixOmics package in R. I found differential gene expression in the fat body at the third instar larval stage, particularly in pathways related to lipid metabolism, calcium …

Ecological And Pathological Applications Of The Heat Shock Response, Taylor Rae Stanley

Theses and Dissertations

The heat shock response (HSR) is a cytoprotective stress response pathway that regulates cellular proteostasis. The HSR is an evolutionarily conserved pathway that is essential for normal cellular functioning. Here, we explore the broad ecological and pathological impacts of the HSR. In an ecological context, we perform gene level analysis of the transcriptomes of two closely related sunfish. We found that the more invasive bluegill sunfish has gene expansions in two HSR gene families, the HSP70 family and the HSP90 family compared to the redear sunfish. These gene expansions were also observed in several other teleost fish species and were …

Investigation Of Reproductive Inhibition During Chronic Heat Stress In C. Elegans, Macy Makenna Nielander

Theses and Dissertations

Nearly all organisms experience heterogeneity in environmental conditions that can negatively impact fitness. A common adaptive strategy to reduce the impact of this stress is called facultative diapause, where development and reproduction are temporarily arrested to promote survival. Facultative diapause is characterized by three major criteria, the arrest must be (i) induced by an unfavorable environmental condition, (ii) reversible, and (iii) driven by genetically regulated mechanisms. The aim of this thesis was to determine whether chronic heat-induced inhibition of egg laying in Caenorhabditis elegans represents a novel form of facultative diapause. It was found that the inhibition of egg-laying is …

Size Matters: The Characterization Of Telomere Function In Germ Cell Development In Danio Rerio, Jessica Macneil

Graduate Doctoral Dissertations

Infertility is a growing problem worldwide. According to the WHO, 48 million couples across the globe suffer from infertility and many couples turn to Assisted Reproductive Technology (ART) to become pregnant. One readout of gamete quality and successful ART is telomere integrity because telomeres are necessary for chromosome movements during meiosis so that the segregation of chromosomes happens correctly. Telomeres are well known for their role in aging; however, they play an important and understudied role during meiosis. In meiosis, telomeres attach to the nuclear envelope (NE) via a protein chain spanning the NE that interacts with cytoplasmic motor proteins, …