Cell and Developmental Biology Commons^™

Sdf-1Α Mediates Primary Tumor Escape In Glioblastoma Through Activation Of Mesenchymal Transitions., Charles T. Froman-Glover

College of Arts & Sciences Senior Theses

Glioblastoma (GBM), a highly aggressive primary brain tumor originating in glial cells, poses a significant challenge due to its rapid growth and invasive nature within healthy brain tissue.

Current treatments involve surgical resection, chemotherapy, and radiation. These treatments alone are not enough to cure this disease, and a better understanding the mechanics of the tumor micro-environment is imperative to furthering the field of cancer research. This research focuses on understanding the tumor microenvironment's impact, specifically investigating the role of stromal cell-derived factor 1 (SDF-1) mechanics on GBM aggressiveness. SDF-1 is known to facilitate disease progression by facilitating chemotaxis toward the …

The Anti-Diabetic Drug Metformin Disrupts Feeding And Sleeping Behaviors In Drosophila Melanogaster., Lucas Fitzgerald

College of Arts & Sciences Senior Theses

Dimethylbiguanide, also known as metformin, is the single most prescribed oral treatment for non-insulin dependent diabetes mellitus, or type 2 diabetes, in Western countries. The primary mechanism of action that metformin acts through is the activation of AMP kinase, an important regulator of energy homeostasis. While the anti-diabetic effects of metformin are well documented, its effects on feeding and sleeping behaviors are not well characterized. Using the model organism Drosophila melanogaster, the mean daily quantity of food consumed was measured and compared between groups treated with several dosages of metformin. Feeding interactions such as meal frequency and length were …

Understanding The Role Of Minor Intron Splicing In Spermatogenesis, Jade Rosado, Kazumasa Takemoto, Rahul Kanadia

Honors Scholar Theses

The minor spliceosome is composed of the unique small nuclear RNAs (snRNA), U11, U12, U4atac, and U6atac, and is necessary for the splicing of less than 0.5% of introns, termed minor introns. Minor intron containing genes (MIGs) regulate diverse processes, one of which is spermatogenesis. Specifically, 111 testis-specific MIGs have been identified, suggesting that minor splicing is necessary for spermatogenesis. To interrogate the role of minor splicing in spermatogenesis, we conditionally ablated the Rnu11 gene, which encodes for the U11 snRNA, in the developing testes via Stra8-iCre, creating a Rnu11^Flx/Flx::Stra8-Cre⁺ mutant. We found, at postnatal …

Connecting Genotype And Phenotype: Investigating The Functional Morphology And Molecular Architecture That Influences Craniofacial Divergence Using Lake Malawi Cichlid Fishes, Leah Delorenzo

All Dissertations

Connecting genotype and phenotype to better understand how species evolve has been a goal of evolutionary developmental biologists over the last 50 years. This dissertation aims to connect genotype and phenotype of the craniofacial skeleton within the adaptive radiation of Lake Malawi cichlids to fortify our understanding of the functional, genetic, and epigenetic factors that contribute to craniofacial divergence. I start with a functional approach using 2D geometric morphometrics to assess craniofacial shape across the Lake Malawi cichlid radiation to bolster our knowledge of the bone phenotypes that are important to niche specialization and are functionally relevant. Next, I use …

Understanding The Functional Role Of Lone Star Tick (Amblyomma Americanum) Threonyl-Trna Synthetase In Reproductive Fitness, Anza Ali

Honors Theses

Introduction: Transfer RNA synthetases are a family of enzymes that catalyze the addition of amino acids to their corresponding transfer RNAs (tRNAs) and play an essential role in protein synthesis. Ticks are obligate hematophagous ectoparasites that rely on prolonged feeding periods to complete their life cycle on a vertebrate host. Tick tRNA synthetases help the tick in continuous protein synthesis for efficient blood feeding and reproductive fitness, thus presenting a potential target for developing new tick control strategies. Studies have been conducted assessing the functionality of different tRNA synthetases such as Valine-tRNA synthetase, Asparagine-tRNA synthetase, Lysine-tRNA synthetase, and Leucine-tRNA synthetase …

College Of Natural Sciences Newsletter, Spring 2024, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Page 1 Dean's Message
Page 2 New Faculty and New Club on Campus
Page 3 2024 URSCAD Awards
Page 4 Day of Scholars 2024
Page 5 SDSU's First Representation at the Association for Anatomy's 2024
Annual Conference
Page 6-7 2024 Honor's College Convocation
Page 8 Other Student Activities
Page 9 Faculty Awards
Page 10-11 Other News
Page 12 2024 Drone Day and American Association of Geographers Convention - Hawaii
Page 13 55th Annual Geography Convention
Page 14 2024 Stethoscope Ceremony
Page 15 Open PRAIRIE Data

A Review Of Rheb Activation Of Mtorc1 And The Great Mystery Of One Missing Gef, Jack Gregory

Senior Honors Theses

The mTORC1 pathway is involved in the regulation of cell growth and translation. The pathway has a complex web of activators and inhibitors to activate mTORC1. mTORC1 is regulated via a small GTPase called Rheb, which interacts directly with mTORC1. This GTPase and its GTPase activating protein (GAP), TSC1/2, have been widely studied to understand how the variety of regulators of mTORC1 interact with these proteins. Despite this, the guanine nucleotide exchange factor (GEF) of Rheb has yet to be identified. This review broadly analyzes Rheb and mTORC1, their structures, regulations, and interactions, and explores the mystery of the missing …

The Role Of The Transcription Factor Cebpa In Regulating Lung Alveolar Type 2 Cell Fate In Vivo, Dalia Hassan

Dissertations and Theses (Open Access)

Cell plasticity can extend across all possible cell types, yet it naturally diminishes as cells progress through differentiation. This plasticity can be reactivated during injury repair, engaging developmental flexibility. Our investigations reveal the critical role of the transcription factor (TF) CEBPA, specific to lung alveolar type 2 (AT2) cells, in modulating AT2 cell plasticity within the mouse lung. We demonstrate that CEBPA constrains AT2 cell plasticity by promoting the AT2 differentiation program and recruiting the lineage-specific TF NKX2-1. Without CEBPA, AT2 cells, in both neonatal and mature, show a diminished AT2 program; however, only neonatal cells re-activate the SOX9 progenitor …

Atlas-Based Analysis Of The Neural Projections From The Lateral Hypothalamic Area To The Lower Brainstem In The Adult Male Rat, Jessica Valeria Salcido Padilla

Open Access Theses & Dissertations

Within the last decade, the number of diseases associated with dysregulation of the neural circuits responsible for energy balance, glucosensing, and feeding control has increased. One brain region containing these circuits is the lateral hypothalamic area (LHA), which plays an important role in the sleep/wake cycle, energy balance, and motivated behavior. Although the LHA has been termed a â??feeding centerâ??, other regions within the hindbrain are known for the regulation of similar functions including energy balance, glucosensing, and feeding control. While many studies have explored and reported projections from the LHA to the hindbrain, few have further investigated the interconnections …

Stability Of Dna In Saliva Evidence Collected With Two Different Swabbing Solutions, Kuanwei Lu

Student Theses

As the significance of trace DNA has increased over time, it has become more important to optimize each process to avoid any loss of genetic material. Factors that could negatively affect the quality and quantity of DNA during transport or storage include environmental temperature, the DNA collection devices, the packaging, and possible contamination. This study compared the DNA stability of saliva stain swabs collected by moistening the swab with deionized water or Sample Keeper and stored at room temperature. Sample Keeper (Microread Genetics, Beijing) is a proprietary buffer marketed as a DNA stabilizing agent. We swabbed 110 saliva stains from …

Advancements In Crispr-Cas9 Gene Editing: Applications And Future Implications For Sickle Cell Disease And Β-Thalassemia Treatment, Swetha Battini

Honors Scholar Theses

This literature review explores the utilization of CRISPR-Cas9 gene editing technology in addressing Sickle Cell Disease (SCD) and Beta-Thalassemia. CRISPR, leveraging the Cas-9 enzyme inspired by bacterial defense mechanisms, serves as a precise molecular tool for targeted genetic modifications. The process involves guide RNA directing Cas-9 to specific DNA sites, allowing for meticulous gene editing. Focusing on the specific applications of CRISPR in SCD and Beta-Thalassemia, the review critically analyzes recent methods, including CRISPR-Cas9 editing targeting the BCL11A enhancer for SCD and the HBG1/HBG2 promoters for both SCD and Beta-Thalassemia. The synthesis of findings highlights the potential and challenges of …

The Role Of Mettl21a In Kras-Driven Cancers, Xiaojie Yang

Dissertations and Theses (Open Access)

Abstract

More than 100 lysine methyltransferases (KMTs) were predicted to be present in the human proteome, and many were implicated in cancer etiology. However, the catalytic activity and substrate specificity for many of these enzymes remain unknown. Our work aimed to explore the role of Methyltransferase like 21A (METTL21A), amember of the little-studied seven β- strand family of candidate lysine methyltransferases (KMTs), and its role in regulating pancreatic ductal adenocarcinoma (PDAC) and lung adenocarcinoma (LUAC) tumorigenesis. Through the meta-analysis of publicly available gene expression datasets, I found that METTL21A is significantly downregulated in PDAC and LUAC versus normal tissue, and …

Oxidative Phosphorylation In Melanoma Brain Metastases: A Regulator Of The Tumor Immune Landscape, Renato A. Guerrieri

Dissertations and Theses (Open Access)

Previously, we demonstrated via RNA-sequencing analysis of murine intracranial melanoma tumors that pharmacologic inhibition of oxidative phosphorylation (OXPHOS) results in increased expression of genes consistent with activated anti-tumor immune responses. The central hypothesis of this dissertation is that OXPHOS plays a critical role in the pathogenesis and immune regulation of melanoma brain metastases (MBMs).

The functional significance of OXPHOS was assessed through genetic inhibition, involving knockout (KO) of key regulatory genes such as Ppargc1a (PGC1a) and Ndfus4 (NDUFS4), a component of mitochondrial complex I. PGC1a KO in an RCAS-TVA mouse model of autochthonous lung and brain tumors developing from primary …

Mast Cells In Mammary Carcinoma, Alexandria M. Ashbaugh

Undergraduate Honors Theses

Breast cancer (BC) is an aggressive disease that takes the lives of thousands of women every year. Although knowledge and treatment of this disease have improved over the years, much is still to be discovered about BC. One area of expertise that we are currently trying to learn more information about is the mast cell (MC) and its role in BC growth and development. The MC is an immune system component discovered in tumors' extracellular matrix (ECM). As a tumor grows within body tissues, the tumor recruits the MC from surrounding connective tissues to the tumor, using signaling cytokines such …

The Effect Of Yamanaka Factors On The Metastatic Potential Of Breast Cancer Cells, Riley Mendonca

Undergraduate Honors Theses

The mortality associated with cancer is most commonly a result of it spreading to other tissues and organs in a process known as metastasis. For carcinomas to do this they must first break through the basement membrane containing them to interact with the stroma. This is known as an epithelial-mesenchymal transition and occurs when carcinomas suppress their original epithelial qualities in order to adopt more mesenchymal ones. This involves cancers dedifferentiating from their original cell type to lose the specialized features that distinguished them and where they came from. As cancers become more invasive, this dedifferentiation becomes more pronounced. Recent …

Epigenetic Modification As A Therapeutic Target In Brafv600e-Mutated Metastatic Colorectal Cancer, Hey Min Lee

Dissertations and Theses (Open Access)

Patients with BRAF^V600E-mutated metastatic colorectal cancer (mCRC) experience a worse prognosis and demonstrate only a 5% response rate to BRAF inhibitor treatment. In this study, adaptive resistance, and a potential combination of standard therapies in BRAF^V600E CRC were unveiled. Intriguingly, a robust association of BRAF^V600E mutation and DNA hypermethylation suggests this is a unique subgroup harboring aberrant epigenetic phenotype. Firstly, DNA methyltransferase (DNMT) inhibitor treatment induced profound DNA hypomethylation in vivo, but minimal change in gene expression due to adaptive elevation of the repressive histone methylation, H3K27me3, leading to compensatory suppression of key tumor suppressor genes, …

Loss Of Ptdss1 In Tumor Cells Improves Anti-Pd-1 Therapy, Jielin Liu

Dissertations and Theses (Open Access)

PTDSS1 (Phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of PTDSS1 in tumor cells increased expression of IFNγ-regulated genes, including B2m, Cxcl9, Cxcl10, and Stat1. Loss of PTDSS1 in tumor cells also led to increased expression of MHC-I, which was associated with increased expression of cytolytic function related genes in CD8⁺ T cells and increased frequency of an iNOS⁺ myeloid subset. A gene signature derived from the iNOS⁺ myeloid …

The In4mer Crispr/Cas12a Multiplex Knockout Platform And Its Applications, Nazanin Esmaeili Anvar

Dissertations and Theses (Open Access)

Discovering synthetic lethal interactions between genes holds the key to uncovering cancer vulnerabilities, enabling the development of more effective drugs for patients. However, identifying these vulnerabilities in the complex genome of human, which comprises thousands of genes, poses a significant challenge. One alternative approach to investigate these interactions involves exploring enriched sources of synthetic lethal interactions, such as paralog pairs. In recent years, a couple of studies have conducted dual-gene knockout experiments on paralog pairs using different approaches to identify synthetic lethal interactions. In this study, we conducted a meta-analysis of CRISPR genetic interaction screens. We identified a candidate set …

Exploring The Role Of Il-1Β/Il-1r In The Pathogenesis Of K-Ras Mutant Lung Cancer, Avantika Krishna

Dissertations and Theses (Open Access)

As the leading cause of cancer-related deaths worldwide, the development of targeted therapeutics to treat lung cancer remains crucial. Non-small cell lung cancer (NSCLC), the most common histological subtype predominantly comprises lung adenocarcinoma with driver mutations in the K-ras oncogene (KM-LUAD). KM-LUAD progression partly occurs through activation of the NF-κB pathway initiating an inflammatory response and creating a pro-tumor microenvironment. Notably, the pro-inflammatory cytokine IL-1β a potent activator and product of the NF-κB pathway is elevated in the lungs and sera of KM-LUAD patients. We have shown that IL-1β blockade promotes an anti-tumor immune phenotype in a mouse model of …

Histone Lysine Methyltransferase Nsd3 Governs Transcriptional Programs That Drive Pancreatic Neuroendocrine Tumors (Pannets), Mary Esmeralda Fuentes

Dissertations and Theses (Open Access)

Pancreatic Neuroendocrine Tumors (PanNETs) are the most common and lethal neuroendocrine malignancies where treatments used in advanced patients have limited efficacy, adverse side effects, and acquire resistance. Thus, there is a critical need to uncover novel precision therapeutics for PanNET patients. Additionally, pre-clinical models that more accurately represent disease are an urgent necessity for translational studies.

This dissertation directly addresses these challenges by identifying histone lysine methyltransferase (KMT) NSD3 as a critical oncogenic driver of PanNETs through di-methylation of histone H3K36 (H3K36me2).

The findings shown in this body of work indicate that H3K36 methylation by NSD3 functions as a transcriptional …