Cell and Developmental Biology Commons^™

Importance Of Specific Nk Cell Subsets For Antitumor Immunity In Hpv+ Cancers, Madison O'Hara

Dissertations and Theses (Open Access)

High-risk type human papillomaviruses (HPV) are associated with genital and oral cancers, and the incidence of HPV+ head and neck squamous cell cancers is fast increasing worldwide. Survival rates for patients with locally advanced disease are poor and variable after standard of care (SOC) treatment. Identifying the antitumor host immune mediators important for treatment response and designing strategies to promote them are essential for improving clinical outcome. The natural killer (NK) cells are a critical component for antitumor innate effector immunity. Among the multitude of activation and inhibitory receptors on immune cells, HLA-DR is recognized as an important activation marker …

Biophysical Model Of Retraction Motor Neurons And Their Modification By Operant Conditioning, Maria Rasheed

Dissertations and Theses (Open Access)

Operant conditioning (OC) is a form of associative learning in which an animal modifies its behavior based on the consequences that follow that behavior. Despite its ubiquity, the underlying mechanisms of OC are poorly understood. Insights into the mechanisms of OC can be obtained by studying Aplysia feeding behavior as it can be modified by OC. This behavior is mediated by a central pattern generator (CPG) network in the buccal ganglia that contains a relatively small number of neurons. This CPG generates rhythmic motor patterns (BMPs) that move food into the gut by closing a tongue-like structure (i.e., radula) during …

Syntaxin-3 Mediates Baseline And Stimulated Mucin Secretion, Brianne Wharton

Dissertations and Theses (Open Access)

There are two rates at which airway epithelial cells secrete mucin. The low baseline rate accounts for ciliary clearance, and the high stimulated rate obstructs airways in protection from helminths or in obstructive pulmonary diseases. The exocytosis of mucins occurs via the four-helix SNARE complex. The SNARE proteins contributing helices are the vesicle-SNARE VAMP, and the target-SNAREs SNAP and Syntaxin. Coiling of the complex fuses the granule and plasma membranes to release mucins into the extracellular space. The VAMP and SNAP isoforms mediating baseline and stimulated secretion are known, but the Syntaxin (Stx) isoform remains unknown.

Three candidate exocytic Stx, …

Mesenchymal Stromal Cell Response To Degenerated Intervertebral Disc-Like Ph, Kyle Cannon

All Dissertations

Intervertebral disc degeneration (IVDD) has become increasingly prevalent and is a common contributing factor to low back pain. There are currently no clinical treatment options for IVDD that alleviate the symptoms of IVDD while simultaneously promoting repair of IVD tissue. One treatment option being explored is intradiscal administration of mesenchymal stromal cells (MSCs). However, the microenvironment of the degenerating IVD places significant stress on both native IVD cells and implanted cells. There are several questions that need to be addressed which may help further inform the development of efficacious intradiscal MSC therapies for IVDD. These questions include: 1) Do MSCs …

Single Cell Pharmacodynamic Modeling Of Cancer Cell Lines, Arnab Mutsuddy

All Dissertations

Cancer is one of the leading causes of disease related death worldwide. Since the discovery of the genomic origins of cancer, targeted therapy has been developed towards specific mutations implicated for oncogenic transformation. However, current standard-of-care for mapping cancer patients to efficacious drug combination is often inadequate. The pathophysiology of tumor progression relies on the dysregulation of biomolecular pathways of which the topology and the dynamics challenge prognosis. Moreover, the overall genomic instability involved in disease states and the resulting inter-patient as well as intra-tumoral heterogeneity challenge rationalization of therapy and clinical decision-making. It highlights the need for the use …

Exploring Novel Nutrient Acquisition Mechanisms For Maintaining Energy Metabolism In Toxoplasma Gondii, Melanie Key

All Dissertations

Toxoplasma gondii is an infectious intracellular parasite that establishes infection within various mammalian hosts, including humans. Toxoplasma infects approximately one-third of the global population, making it an impactful pathogen of study. T. gondii is the causative agent of toxoplasmosis, an opportunistic infection that causes severe illness or fatality in immunocompromised individuals or pregnant women. The parasite possesses a very effective invasion strategy, allowing it to cross different tissue types to disseminate infection across the placental and blood-brain barrier. Although there are a few treatments for acute toxoplasmosis, these drugs can produce adverse side effects. These options are not effective against …

The Expression Of Recombinant Cas9 Proteins In E. Coli Bl21(De3) Strains, Morgan Reese

Graduate Theses and Dissertations

Abstract Extensively used for genome editing, CRISPR-Cas9 is a relatively new tool that has made a major impact in the genomic engineering landscape. Due to this, the production of CRISPR proteins that are not commercially available can limit research applications. Here, we present methods for optimizing laboratory scale production of CRISPR proteins including Cas9. The method uses IPTG to induce gene expression of the specified Cas9 and nickel column purification to isolate proteins. CRISPR proteins are validated for purity by SDS-PAGE gel, western blot, and for activity by in vitro digestion. We thoroughly validate and compare the effectiveness of BL21(DE3) …

Qualitative Assessment Of Human Embryonic- And Induced Pluripotent Stem Cell Derived Neural Stem Cells Under Cgmp Methods, Michelle Hernandez

Electronic Theses, Projects, and Dissertations

Neural stem cell therapies represent a promising tool for the development of regenerative medicine and are being tested in clinical trials for several neurological disorders. However, the clinical applicability of stem cell therapies is dependent on the implementation of current good manufacturing practices (cGMPs) to ensure the quality, safety, and consistency that stem cell products need to meet FDA regulatory requirements. As such, there is a need for a shift to xeno-free methodologies so experimental conditions are cGMP compliant. The purpose of this study is to test a GMP compatible production method to generate multipotent neural stem cells (NSCs) from …

Differential Expression Of Microrna Mir-145 And Mir-155 Downstream Targets In Oral Cancers Exhibiting Limited Chemotherapy Resistance, Conner Belnap

UNLV Theses, Dissertations, Professional Papers, and Capstones

Background: New evidence has suggested that non-coding microRNAs play a significant role in mediating and modulating chemotherapy resistance, particularly among oral cancers. One recent study found that the expression of miR-145 and lack of miR-155 expression strongly correlated with a limited chemotherapy resistance to Cisplatin, 5-Fluorouracil and Paclitaxel , although the mechanism(s) responsible for these observations remain unidentified.

Methods: Using commercially available cell lines of oral squamous cell carcinoma (OSCC), RNA was isolated using phenol:chloroform extraction. The isolated RNA was converted into cDNA by reverse transcription and subsequently screened for the presence or absence of downstream targets of miR-145 and …

Regulation Of Embryonic Eye Regrowth In Xenopus Laevis, Dylan Guerin

UNLV Theses, Dissertations, Professional Papers, and Capstones

Regrowth of lost organs and tissues is an amazing ability that some animals possess. For regrowth to be considered full, the organism must regrow the organ or tissue to a state that is structurally and functionally similar to that which was lost. The ability of an organism to regrow lost or damaged tissue varies among animals, both in the mechanisms utilized to achieve regrowth, and in what body parts can be regrown. Potentially even closely related species can vary wildly in regenerative ability. Therefore, regenerative research can look to other tissues and organisms for direction in elucidating the mechanisms through …

Cellular Mechanisms Of Embryonic Eye Regrowth In Xenopus Laevis, Randolph L. Grell

UNLV Theses, Dissertations, Professional Papers, and Capstones

The African Clawed Frog, Xenopus laevis, has been an indispensable model organism for over 100 years in the study of embryogenesis and development. In recent years, this vertebrate model has emerged as a robust tool for deciphering the cellular and molecular mechanisms underlying various modes of tissue, limb, and organ regeneration. In the context of eye repair, Xenopus offers a unique model, where the adult frog eye has limited regenerative capacity compared to its pre-metamorphic embryonic and tadpole forms, which exhibit a robust capacity for regrowth. Understanding the intricate molecular mechanisms that underlie this developmental shift in regrowth ability …

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, …

Decorin Suppresses Tumor Lymphangiogenesis: A Mechanism To Curtail Cancer Progression, Dipon K. Mondal, Christopher Xie, Gabriel J. Pascal, Simone Buraschi, Renato V. Iozzo

Kimmel Cancer Center Faculty Papers

The complex interplay between malignant cells and the cellular and molecular components of the tumor stroma is a key aspect of cancer growth and development. These tumor-host interactions are often affected by soluble bioactive molecules such as proteoglycans. Decorin, an archetypical small leucine-rich proteoglycan primarily expressed by stromal cells, affects cancer growth in its soluble form by interacting with several receptor tyrosine kinases (RTK). Overall, decorin leads to a context-dependent and protracted cessation of oncogenic RTK activity by attenuating their ability to drive a prosurvival program and to sustain a proangiogenic network. Through an unbiased transcriptomic analysis using deep RNAseq, …

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 …

Investigating Vital Neutrophil Extracellular Trap Pathogen Response In Neutropenic Individuals, Ryan Illig

Thinking Matters Symposium

Neutrophils, also called polymorphonuclear leukocytes (PMNs), constitute the majority of innate immune cells. These cells possess a complex arsenal of functions that allow them to detect and eliminate a broad spectrum of pathogens. Neutropenia is characterized by decreased levels of neutrophils in the bloodstream, typically falling below the normal range. Moderate to severe neutropenia can increase the risk of pathogenic infections and without treatment can be life-threatening. Although the concentration of neutrophils in neutropenic individuals is decreased, upon activation, neutrophils still release neutrophil extracellular traps (NETs). NETs are pivotal in combating a spectrum of pathogens through their non-selective nature. Overreactive …

Treatment Of Warthin’S Tumors Of The Parotid Gland With Radiofrequency Ablation: A Systematic Review Of The Current Literature, Kenny Do, Eric Kawana, Sisi Tian, Jo-Lawrence Bigcas

School of Medicine Faculty Research

Objective: Warthin’s tumors of the parotid gland can be safely observed. Definitive treatment usually requires parotidectomy under general anesthesia. The decision to operate on Warthin’s tumors of the parotid gland can be complicated in patients who wish to avoid risks of surgery and general anesthesia. This systematic review explores the potential of radiofrequency ablation (RFA) as a minimally invasive alternative. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model was used to collect 3 relevant studies that focused on RFA treatment for Warthin’s tumors. The cumulative averages for tumor size and cosmetic scores were then quantified for …

The Anatomical Embodiment Of Morning Routines In The Reduction Of Anxiety: An Intervention, Natalie Wright

Expressive Therapies Capstone Theses

The topic under investigation is whether physically embodying a morning routine that was designed through the lens of Laban Bartenieff Movement Analysis (LBMA) will reduce daily symptoms of individuals diagnosed with Generalized Anxiety Disorder.

Since morning routines play a significant part in one’s preparation for the day, I created an individualized LBMA morning routine for a specific client to embody. In addition to the routine, the client documented the process of their anxiety levels on a weekly basis. This client was a white, female, 19-year-old, lesbian college student who was previously diagnosed with Generalized Anxiety Disorder (GAD). The movement analysis …

Annotation Of Hypothetical Genes In Lactococcus Lactis Ssp. Il403, Jennifer A. Tangires

Student Scholar Showcase

The human gastrointestinal tract (GIT) harnesses various microbial organisms involved in almost all processes of physiological homeostasis, among these are lactic acid bacteria (LAB). These bacteria, almost all of which belong to the order Lactobacillales, are able to produce lactic acid, and play an important role in food preservation because they produce bacteriocins. Bacteriocins are antimicrobial proteins that are used to fight off related bacteria in their environment that are competing for the same resources. This study focuses on a specific LAB strain, Lactococcus lactis ssp. IL1403 where 21.9% of its predicted genes have not yet been assigned a function. …