Cell and Developmental Biology Commons^™

Pharmacological Inhibition Of Histone Methyltransferase G9a Affects Expression Of Citron Kinase Target Genes In Neural Stem Cells, Nicholas Heliotis

Honors Scholar Theses

Regulated repression of gene expression by post-translational modification of histones is required for normal development. The histone methyltransferase G9a is essential for embryonic development, and we have shown that phosphorylation of G9a by the CitK, a gene required for normal CNS development, gates gene repression and dimethylation of histone H3 at lysine 9 (H3K9me2) in neural progenitors. CitK and G9a co-localize to promoter regions of genes up-regulated in CitK null cells. CitK mutant progenitors lack H3K9me2 at promoter regions of up-regulated genes, and re-expression of CitK restores both repression of gene expression and H3K9me2 occupancy. In this thesis we examine …

A Search For Light-Detecting Proteins In The Free-Living Protist, Tetrahymena Thermophila: Does Tetrahymena Have Opsin-Like Or Bacteriorhodopsin-Like Proteins?, Jillian Marie Rainville

Senior Honors Projects

Tetrahymena is a genus of ciliated protozoans, a diversified lineage of unicellular eukaryotes. They are freshwater organisms, and generally inhabit streams, lakes, and ponds. Tetrahymena thermophila is commonly studied as a model cell because of its unique variety of complex and specialized cell structures and processes, which are similar to those of higher animals.

G-protein-coupled receptors (GPCRs) are transmembrane proteins that transduce stimuli from outside of the cell into intracellular signals, through the interaction of their intracellular domains with heterotrimeric G proteins. GPCRs make up a vast protein family that includes a variety of subfamilies with distinct functions. They are …

Analysis Of The Chondroitinase Operon Of Flavobacterium Columnare, Erin L. Sorlien

Senior Honors Projects

Analysis of the chondroitinase operon of Flavobacterium columnare

Erin Sorlien

Major

Cell and Molecular Biology, Chemistry

Advisor

Dr. David R. Nelson

Date

May 2, 2013

Keywords

Flavobacterium columnare, columnaris disease, chondroitin AC lyase, complementation, csl operon

Abstract
Flavobacterium columnare, an opportunistic bacterial pathogen of fish, is the causative agent of columnaris disease (CD). The bacterium is a Gram-negative rod that exhibits gliding motility and avidly forms biofilms. CD affects both wild and cultured freshwater fish, and continues to cause large economic losses to the fish farming industry. According to an investigation conducted by the National Animal Health Monitoring System, CD …

Oxidative Stress For An Acute Bout Of Bikram Yoga In Healthy, Trained Adults, Kimberly Anne Trocio

UNLV Theses, Dissertations, Professional Papers, and Capstones

BACKGROUND:Generation of free radicals resulting in oxidative damage has been linked to cellular damage, aging, and human disease. Many studies have reported that physical exercise can contribute to oxidative stress. Further, exercise in a hyperthermic environment can promote additional oxidative stress. It is important to consider that practices in yoga may be beneficial in reducing oxidative stress according to some studies. The compound effects of exercise and hyperthermic exposure are experienced in the practice of Bikram yoga, the original "hot" yoga. Because Bikram yoga and other hot exercise classes are an increasingly growing fitness trend, it is necessary to investigate …

A Novel Therapeutic Approach In Breast And Hematopoietic Cancers: Inhibition Of Sh2-Domain Containing Inositol 5' Phosphatase (Ship), Amamda Balch

Renée Crown University Honors Thesis Projects - All

Aberrant hyperactivation of the phosphatidylinositol 3-kinase (PI3K) cell-signaling pathway, one of the most prominent cell growth, proliferation and survival pathways in the human body, has been observed in many forms of cancer. Upon deregulation, this pathway can facilitate the evasion of programmed cell death, the stimulation of autonomous growth, and the evasion of regular growth-inhibitory signals. While it was initially believed that the dephosphorylation activity of lipid phosphatases served to counteract the pathway by hydrolyzing phosphatidylinositol(3,4,5)trisphosphate (PtdIns(3,4,5)P₃) to phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P₂), emerging evidence suggests that SH2-domain containing inositol 5’ phosphatase 1 and 2 (SHIP1/2) may in fact …

Mechanisms Underlying The Heterogeneous Sensitivities Of Cancer Cells To Proteasome Inhibitors, Matthew C. White

Dissertations and Theses (Open Access)

The mechanisms underlying cellular response to proteasome inhibitors have not been clearly elucidated in solid tumor models. Evidence suggests that the ability of a cell to manage the amount of proteotoxic stress following proteasome inhibition dictates survival. In this study using the FDA-approved proteasome inhibitor bortezomib (Velcade®) in solid tumor cells, we demonstrated that perhaps the most critical response to proteasome inhibition is repression of global protein synthesis by phosphorylation of the eukaryotic initiation factor 2-α subunit (eIF2α). In a panel of 10 distinct human pancreatic cancer cells, we showed marked heterogeneity in the ability of cancer cells to induce …

Targeting Histone Deacetylases (Hdac) For The Treatment Of Soft Tissue Sarcoma, Gonzalo Lopez

Dissertations and Theses (Open Access)

Targeting Histone deacetylases (HDAC) for the treatment of genetically complex soft tissue sarcoma

Histone deactylase inhibitors (HDACi) are a new class of anticancer therapeutics; however, little is known about HDACi or the individual contribution of HDAC isoform activity in soft tissue sarcoma (STS). We investigated the potential efficacy of HDACi as monotherapy and in combination with chemotherapy in a panel of genetically complex STS. We found that HDACi combined with chemotherapy significantly induced anti-STS effects in vitro and in vivo. We then focused our study of HDACi in malignant peripheral nerve sheath tumor (MPNST), a subtype of highly aggressive, …

Characterizing The Role Of Cortactin In Actin Pedestal Assembly By Enterohemorrhagic Escherichia Coli (Ehec), Sarah E. Grout

Honors Scholar Theses

Enterohemorrhagic Escherichia coli (EHEC) is a major foodborne cause of bloody diarrhea and renal failure. During colonization of the intestine, EHEC injects the transmembrane receptor protein Tir and the cytoplasmic effector protein EspFU into host cells to reorganize the actin cytoskeleton into adhesion “pedestals.” EspFU has been shown to bind and activate the actin nucleation factor N-WASP to drive actin polymerization into pedestals. However, EspFU can still assemble pedestals in cells lacking N-WASP, suggesting that this effector protein is able to also trigger N-WASP-independent pathways of actin polymerization during infection. Cortactin is an atypical nucleation factor that localizes to pedestals, …

In Vitro Characterization Of Avian Influenza Virus Isolates With A Truncated Ns1 Gene Segment, Aaron Dick

Honors Scholar Theses

Avian Influenza Virus represents a significant threat to the world poultry population, and is a potential threat to humans due to the possibility of cross-species AIV infection. Our approach is to characterize a number of avian virus populations with respect to their content of biologically active particles that include hemagglutinating particles (HAP), plaque forming particles (PFP), interferon inducing particles (IFP), interferon induction-suppressing particles (ISP), defective-interfering particles (DIP), cell-killing particles (CKP) and non-infectious cell killing particles (niCKP) using unique in vitro assays developed for avian influenza virus in the Marcus-Sekellick Laboratory. Specifically, we will use a strain of Avian influenza virus, …

Characterization Of Aebp2 Mutant Mice, Arundhati Bakshi

Honors Capstones

No abstract provided.

Unexpected Phylogenetic Positions Of The Genera Rupirana And Crossodactylodes Reveal Insights Into The Biogeography And Reproductive Evolution Of Leptodactylid Frogs, Antoine Foquet, Boris Leonardo Blotto, Maximiliano Manuel Maronna, Vanessa Kruth Verdade, Flora Acuña Juncá, Rafael O. De Sá, Miguel Trefaut Rodrigues

Biology Faculty Publications

Despite major progress in deciphering the amphibian tree of life by molecular phylogenetics, we identified two questions remaining to be answered regarding relationships within Hyloidea, the clade of South American origin that comprises most extant anuran diversity. A few genera like Rupirana and Crossodactylodes have enigmatic phylogenetic positions, and relationships among major lineages within some families like Leptodactylidae remain ambiguous. To resolve these specific questions we used two approaches (1) a complete matrix approach representing >6.6 kb, including most major Hyloidea lineages (61 terminals) combining different methods of phylogenetic reconstruction and measures of node support; and (2) a supermatrix approach …

Molecular Mechanisms Of Vascular Disease In Patients With Rare Variants In Myh11, Callie Kwartler

Dissertations and Theses (Open Access)

Thoracic aortic aneurysms and dissections (TAAD) are the primary disease affecting the thoracic ascending aorta, with an incidence rate of 10.4/100,000. Although about 20% of patients carry a mutation in a single gene that causes their disease, the remaining 80% of patients may also have genetic factors that increase their risk for developing TAAD. Many of the genes that predispose to TAAD encode proteins involved in smooth muscle cell (SMC) contraction and the disease-causing mutations are predicted to disrupt contractile function. SMCs are the predominant cell type in the ascending aortic wall. Mutations in MYH11, encoding the smooth muscle …

Oxidative Stress Based Strategies For Enhancing The Efficacy Of Histone Deacetylase Inhibitors (Hdaci), Nilsa Rivera-Del Valle

Dissertations and Theses (Open Access)

Histone deacetylase inhibitors (HDACi) are anti-cancer drugs that primarily act upon acetylation of histones, however they also increase levels of intracellular reactive oxygen species (ROS). We hypothesized that agents that cause oxidative stress might enhance the efficacy of HDACi. To test this hypothesis, we treated acute lymphocytic leukemia cells (ALL) with HDACi and adaphostin (ROS generating agent). The combination of two different HDACi (vorinostat or entinostat) with adaphostin synergistically induced apoptosis in ALL. This synergistic effect was blocked when cells were pre-treated with the caspase-9 inhibitor, LEHD. In addition, we showed that loss of the mitochondrial membrane potential is the …

The P63 Isoform ∆Np63Α Inhibits Epithelial – Mesenchymal Transition By Promoting The Expression Of Mir-205 In Human Bladder Cancer Cells, Mai Tran

Dissertations and Theses (Open Access)

p63, a p53 family member, is a transcription factor that has complex roles in cancer. This study focuses on the role of the ∆Np63α isoform in bladder cancer (BC). Epithelial – mesenchymal transition (EMT) is a physiological process that plays an important part in metastasis and drug resistance. At the molecular level, EMT is characterized by the loss of the epithelial marker E-cadherin, and the acquisition of the transcriptional repressors of E-cadherin (ZEB1, ZEB2, TWIST, SNAI1 and SNAI2). Recent publications highlight the role of microRNAs belonging to the miR-200 family and miR-205 in preventing EMT through suppression of ZEB1 and …

The Role Of Nucleolin In B-Cell Lymphomas And Fas-Mediated Apoptotic Signaling, Jillian F. Wise

Dissertations and Theses (Open Access)

The death receptor Fas has a key role in mediating homeostasis, elimination of defective cells and more recently implicated in cancer promotion. Many effective anti-cancer therapies depend on Fas-mediated apoptosis to eradicate tumor cells and ineffective Fas-apoptotic signaling is a basis for primary as well as acquired resistance to chemotherapy. We hypothesized that Fas is subjected to direct regulation by inhibitory proteins attained by cancer cells. To screen for potential binding modulators of Fas, we analyzed lymphoma cells for Fas binding proteins. This purification scheme identified high scoring peptides derived from nucleolin, a nuclear protein known to be overexpressed in …

Galectin-3 Enhances The Malignant Melanoma Phenotype By Regulating Autotaxin, Russell R. Braeuer

Dissertations and Theses (Open Access)

In melanoma patient specimens and cell lines, the over expression of galectin-3 is associated with disease progression and metastatic potential. Herein, we have sought out to determine whether galectin-3 affects the malignant melanoma phenotype by regulating downstream target genes. To that end, galectin-3 was stably silenced by utilizing the lentivirus-incorporated small hairpin RNA in two metastatic melanoma cell lines, WM2664 and A375SM, and subjected to gene expression microarray analysis. We identified and validated the lysophospholipase D enzyme, autotaxin, a promoter of migration, invasion, and tumorigenesis, to be down regulated after silencing galectin-3. Silencing galectin-3 significantly reduced the promoter activity of …

Acceleration Of The Panin Development In Mice Expressing Oncogenic K-Ras Due To A High Fat Diet, Bincy Philip

Dissertations and Theses (Open Access)

Obesity is postulated to be one of the major risk factors for pancreatic cancer, and recently it was indicated that an elevated body mass index (BMI correlates strongly with a decrease in patient survival. Despite the evident relationship, the molecular mechanisms involved are unclear. Oncogenic mutation of K-Ras is found early and is universal in pancreatic cancer. Extensive evidence indicates oncogenic K-Ras is not entirely active and it requires a triggering event to surpass the activity of Ras beyond the threshold necessary for a Ras-inflammation feed-forward loop. We hypothesize that high fat intake induces a persistent low level inflammatory response …

Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu

Dissertations and Theses (Open Access)

CD8⁺ cytotoxic T lymphocytes (CTL) frequently infiltrate tumors, yet most melanoma patients fail to undergo tumor regression. We studied the differentiation of the CD8⁺ tumor-infiltrating lymphocytes (TIL) from 44 metastatic melanoma patients using known T-cell differentiation markers. We also compared CD8⁺ TIL against the T cells from matched melanoma patients’ peripheral blood. We discovered a novel subset of CD8⁺ TIL co-expressing early-differentiation markers, CD27, CD28, and a late/senescent CTL differentiation marker, CD57. This CD8⁺CD57⁺ TIL expressed a cytolytic enzyme, granzyme B (GB), yet did not express another cytolytic pore-forming molecule, perforin (Perf). In …

Investigating The Roles Of The P63 Isoforms In The Microrna Biogenesis Pathway, Deepavali Chakravarti

Dissertations and Theses (Open Access)

MicroRNAs play roles in various biological processes like development, tumorigenesis, metastasis and pluripotency. My thesis work has demonstrated roles for p63, a p53 family member, in the upstream regulation of microRNA biogenesis. The p63 gene has a complex gene structure and has multiple isoforms. The TAp63 isoforms contain an acidic transcription activation domain. The ΔNp63 isoforms, lack the TA domain, but have a proline rich region critical for gene transactivation. To understand the functions of these isoforms, the Flores lab generated TAp63 and ΔNp63 conditional knock out mice. Using these mice and tissues and cells from these mice we have …

The Role Of Type I Insulin-Like Growth Factor Receptor Signaling In Breast Cancer Brain Metastasis, Sandra M. Saldana

Dissertations and Theses (Open Access)

Brain metastasis is a common cause of mortality in cancer patients. Approximately 20-30% of breast cancer patients acquire brain metastasis, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF- IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that the IGF-IR signaling axis is constitutively active in brain-seeking sublines of breast cancer cells, driving an increase in in vitro metastatic properties. We demonstrate that IGF-IR signaling is activated in an autocrine manner …