Cell and Developmental Biology Commons^™

Cd277 Is A Negative Co-Stimulatory Molecule Universally Expressed By Ovarian Cancer Microenvironmental Cells, Juan R. Cubillos-Ruiz, Diana Martinez, Uciane K. Scarlett, Melanie R. Rutkowski, Yolanda C. Nesbeth, Ana L. Camposeco-Jacobs, Jose R. Conejo-Garcia

Dartmouth Scholarship

CD277, a member of the butyrophilin subfamily 3 (BTN3), shares significant sequence similarities and predicted common structural features with inhibitory B7-H4 and other members of the B7 superfamily. Here we report that CD277 is consistently expressed in stromal, as well as tumor cells in the microenvironment of human advanced ovarian carcinoma specimens, both of primary and metastatic origin. MHC-II+ myeloid antigenpresenting leukocytes (dendritic cells and macrophages) express significantly higher levels of surface CD277, compared to other tumor-infiltrating leukocyte subsets, and this expression is significantly up-regulated by multiple common tumor microenvironmental signals, including VEGF and CCL3. Most importantly, engagement of CD277 …

Repression Of Wnt Signaling By A Fer-Type Nonreceptor Tyrosine Kinase, Aaron P. Putzke

Biology Faculty Scholarship

The Wnt signaling pathway must be properly modulated to ensure an appropriate output: pathological conditions result from either insufficient or excessive levels of Wnt signal. For example, hyperactivation of the Wnt pathway is associated with various cancers and subnormal Wnt signaling can lead to increased invasiveness of tumor cells. We found that the Caenorhabditis elegans ortholog of the Fer nonreceptor tyrosine kinase, FRK-1, limits Wnt signaling by preventing the adhesion complex-associated β-catenin, HMP-2, from participating in Wnt-dependent specification of the endoderm during embryogenesis. Removal of FRK-1 function results in relocalization of HMP-2 to the nucleus of epidermal cells, and allows …

Distinct Macrophage Subpopulations Regulate Viral Encephalitis But Not Viral Clearance In The Cns, Christina D. Steel, Woong-Ki Kim, Larry Sanford, Laurie Wellman, Sandra Burnett, Nico Van Rooijen, Rochard P. Ciavarra

Biological Sciences Faculty Publications

Intranasal application of vesicular stomatitis virus (VSV) induces acute encephalitis characterized by a pronounced myeloid and T cell infiltrate. The role of distinct phagocytic populations on VSV encephalitis was therefore examined in this study. Ablation of peripheral macrophages did not impair VSV encephalitis or viral clearance from the brain, whereas, depletion of splenic marginal dendritic cells impaired this response and enhanced morbidity/mortality. Selective depletion of brain perivascular macrophages also suppressed this response without altering viral clearance. Thus, two anatomically distinct phagocytic populations regulate VSV encephalitis in a non-redundant fashion although neither population is essential for viral clearance in the CNS. …

Role Of Ampk In The Upregulation Of Steroidogenic Acute Regulatory Protein In The Zona Fasciculata Of The Adrenal Cortex, Adam Wesley Dayton

Theses and Dissertations

Cortisol is a glucocorticoid produced by the zona fasciculata (ZF) of the adrenal cortex. Traditionally, cortisol production and release was seen as being regulated strictly by adrenocorticotropic hormone (ACTH). While this is true of baseline cortisol levels and in response to acute mental stress, the picture is somewhat more complicated in other situations.Interleukin-6 (IL-6) contributes to the maintenance of cortisol levels in situations of prolonged immune or inflammatory stress. AMP activated protein kinase (AMPK) was investigated as a possible mediator of the action of IL-6 or as an independent actor in raising cortisol levels in response to hypoxemic or hypoglycemic …

The Effects Of Growth Hormone In The Inner Ear Of Zebrafish (Danio Rerio) During Hair Cell Regeneration, Chia-Hui Lin

Masters Theses & Specialist Projects

Although deafness is a universal problem, effective treatments have remained elusive. In order to develop potential treatments, an overall understanding of the cellular process of auditory hair cell regeneration, which occurs in fish but not mammals, must be established. A previous microarray analysis and qRT-PCR validation of noise-exposed zebrafish showed that growth hormone (GH) was significantly upregulated during the process of auditory hair cell regeneration. Thus, GH may play an important role during hair cell regeneration. However, cellular effects of exogenous GH in the zebrafish auditory hair cell regeneration have not been examined after noise exposure. To understand the effect …

The Role Of Tyrosine Phosphorylation In The Functions Of The Tumor Suppressor Gprc5a, Xiaofeng Lin

Dissertations and Theses (Open Access)

The retinoic acid inducible G protein coupled receptor family C group 5 type A (GPRC5A) is expressed preferentially in normal lung tissue but its expression is suppressed in the majority of human non-small cell lung cancer cell lines and tissues. This differential expression has led to the idea that GPRC5A is a potential tumor suppressor. This notion was supported by the finding that mice with a deletion of the Gprc5a gene develop spontaneous lung tumors. However, there are various tumor cell lines and tissue samples, including lung, that exhibit higher GPRC5A expression than normal tissues and some reports by other …

Genetic Analysis Of The Function Of The Drosophila Doublesex-Related Factor Dmrt93b, Diana O'Day

Dissertations and Theses (Open Access)

DMRT (Doublesex and Mab-3 related transcription factor) proteins generally associated with sexual differentiation in many organisms share a common DNA binding domain and are often expressed in reproductive tissues. Aside from doublesex, which is a central factor in the regulation of sex determination, Drosophila possesses three different dmrt genes that are of unknown function. Because the association with sexual differentiation and reproduction is not universal and some DMRT proteins have been found to play other developmental roles we chose to further characterize one of these Drosophila genes. We carried out genetic analysis of dmrt93B, which was previously found to be …

Defining The Role Of Il-15 Trans-Presentation By Distinct Cell-Types During The Development And Homeostasis Of Natural Killer And Invariant Natural Killer T Cells, Eliseo F. Castillo

Dissertations and Theses (Open Access)

The immuno-regulatory functions displayed by NK and iNKT cells have highlighted their importance as key lymphocytes involved in innate and adaptive immunity. Therefore, understanding the dynamics influencing the generation of NK and iNKT cells is extremely important. IL-15 has been shown to provide a critical signal throughout the development and homeostasis of NK and iNKT cells; however, the cellular source of IL-15 has remained unclear. In this investigation, I provide evidence that the cell-type providing IL-15 to NK and iNKT cells via trans-presentation is determined by the tissue site and the maturation status of NK and iNKT cells. For NK …

Loss Of Gprc5a Enhances Survival In Normal And Malignant Lung Epithelial Cells By Eliciting Persistent Stat3 Activation Induced By Autocrine Lif, Yulong Chen

Dissertations and Theses (Open Access)

Signal transduction and activator of transcription 3 (Stat3) is activated by cytokines and growth factors in many cancers. Persistent activation of Stat3 plays important role in cell growth, survival, and transformation through regulating its targeted genes.

Previously, we found that mice with a deletion of the G protein-coupled receptor, family C, group 5, member a (Gprc5a) gene develop lung tumors indicating that Gprc5a is a tumor suppressor. In the present study, we examined he mechanism of Gprc5a-mediated tumor suppression. We found that epithelial cells from Gprc5a knockout mouse lung (Gprc5a^-/- cells) survive better in vitro in medium deprived …

Immune Recognition Of Self Nucleic Acids Driven By Endogenous Antimicrobial Peptides: Role In Autoimmunity, Dipyaman Ganguly

Dissertations and Theses (Open Access)

Innate immune recognition of extracellular host-derived self-DNA and self-RNA is prevented by endosomal seclusion of the Toll-like receptors (TLRs) in the dendritic cells (DCs). However, in psoriasis plasmacytoid dendritic cells have been found to be able to sense self-DNA molecules in complex with the endogenous cationic antimicrobial peptide LL37, which are internalized into the endosomal compartments and thus can access TLR9. We investigated whether this endogenous peptide can also interact with extracellular self-RNA and lead to DC activation. We found that LL37 binds self-RNA as well as self-DNA going into an electrostatic interaction; forms micro-aggregates of nano-scale particles protected from …

Artemis Interacts With The Cul4a Ubiquitin E3 Ligase Complex And Regulates The Cell Cycle Progression, Yiyi Yan

Dissertations and Theses (Open Access)

Artemis, a member of the SNM1 gene family, is one of the six known components of the non-homologous end joining pathway. It is a multifunctional phospho-protein that has been shown to be modified by the phosphatidylinositol 3-kinases (PIKs) DNA-PKcs, ATM and ATR in response to a variety of cellular stresses. Artemis has important roles in V(D)J recombination, DNA double strand breaks repair and damage-induced cell-cycle checkpoint regulation. The detailed mechanism by which Artemis mediates its functions in these cellular pathways needs to be further elucidated. My work presented here demonstrates a new function for Artemis in cell cycle regulation as …

Nherf1 – New Modifier Of Colorectal Cancer Progression, Yuho Hayashi

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) develops from multiple progressive modifications of normal intestinal epithelium into adenocarcinoma. Loss of cell polarity has been implicated as an early event in this process, but the molecular players involved are not well known. NHERF1 (Na+/H+ Exchanger Regulatory Factor 1) is an adaptor protein with apical membrane localization in polarized epithelia. In this study, we tested our hypothesis that NHERF1 plays a role in CRC. We examined surgical CRC resection specimens for changes in NHERF1 expression, and modeled these changes in two- and three-dimensional (2D and 3D) Caco-2 CRC cell systems. NHERF1 had significant alterations from normal …

E2f1 And Tumor Suppression: The Role Of P21, Mirnas, And The Dna Damage Response, Regina L. Weaks

Dissertations and Theses (Open Access)

E2F1 is a multi-faceted protein that has roles in a number of important cellular processes including cell cycle regulation, apoptosis, proliferation, and the DNA damage response (DDR). Moreover, E2F1 has opposing roles in tumor development, acting as either a tumor suppressor or an oncogene depending on the context. In human cancer, E2F1 is often deregulated through aberrations in the Rb-p16INK4a-cyclin D1 pathway. In these studies we examined three mechanisms by which E2F1 might mediate its tumor suppressive properties: p21-induced senescence, miRNAs, and the DNA damage response. We found that E2F1 acts as a tumor suppressor in response to ras activation …

Role And Regulation Of Epha2 In Pancreatic Cancer, Pavel A. Levin

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cancer cause of death in the US. Gemcitabine is the first-line therapy for this disease, but unfortunately it shows only very modest benefit. The focus of the current study was to investigate the role and regulation of EphA2, a receptor tyrosine kinase expressed in PDAC, to further understand this disease and identify new therapeutic targets.

The role of EphA2 was determined in PDAC by siRNA mediated silencing. In combination with gemcitabine, silencing of EphA2 caused a dramatic increase in apoptosis even in highly resistant cells in vitro. Furthermore, EphA2 silencing was found …

Regulation Of Morphogenesis In Filamentous Fungi, Haoyu Si

School of Biological Sciences: Dissertations, Theses, and Student Research

One of the distinguishing features of fungal cells is their highly polarized model of growth. Both yeast cells and hyphal cells grow by cell surface expansion at specified cortical sites. Although the same general mechanisms are likely to be involved in controlling the establishment of hyphal polarity in budding yeast and filamentous fungi, it is noticeable that hyphal cells are organized in a fundamentally different manner to yeast dells. For example, hyphal cells organize formins, septins and actins at the division site while simultaneously retain the same machinery at the tip; whereas yeast cells undergo a transient period of isotropic …

Genetic Polymorphisms Of Cyp2e1, Gstp1, Nqo1 And Mpo And The Risk Of Nasopharyngeal Carcinoma In A Han Chinese Population Of Southern China, Xiuchan Guo, Yi Zeng, Hong Deng, Jian Liao, Yuming Zheng, Ji Li, Bailey Kessing, Stephen J. O'Brien

Biology Faculty Articles

Background

Southern China is a major area for endemic nasopharyngeal carcinoma (NPC). Genetic factors as well as environmental factors play a role in development of NPC. To investigate the roles of previously described carcinogen metabolism gene variants for NPC susceptibility in a Han Chinese population, we conducted a case-control study in two independent study population groups afflicted with NPC in Guangdong and Guangxi Provinces of southern China.

Methods

Five single nucleotide polymorphisms (SNPs) of CYP2E1-rs2031920, CYP2E1-rs6413432, GSTP1-rs947894, MPO-rs2333227 and NQO1-rs1800566 were genotyped by PCR-based RFLP, sequencing and TaqMan assay in 358 NPC cases and 629 …

Anti-Depressive And Anti-Obesity Changes Following Either Dietary Isoflavone Treatment Or Injection Treatment With The Isoflavonoid Equol: Positive Response Dependent On Animal Age And Ovarian Status In Female Long Evans Rats, Crystal Blake

Theses and Dissertations

Two conditions associated with ovarian depletion are increased potential for depressive episodes and increased abdominal weight gain. In five different experiments we examined the effect of soy-containing diets or equol injections on depression, serotonin levels, weight gain (BW) and white adipose tissue (WAT) deposition of female Long-Evans rats in various stages of life. Rats were intact, ovariectomized or experienced natural ovarian failure (NOF). While this paper will present each experiment, only experiment 5 is outlined here due to space limitations. From conception the rats were exposed to either a soy-rich (Phyto-600) or low-soy diet (Phyto-low). Animals experienced NOF at approximately …

Chronic Amp-Activated Protein Kinase Activation And A High-Fat Diet Have An Additive Effect On Mitochondria In Rat Skeletal Muscle, Natasha Fillmore

Theses and Dissertations

Factors that stimulate mitochondrial biogenesis in skeletal muscle include AMPK, calcium, and circulating FFAs. Chronic treatment with either AICAR, a chemical activator of AMPK, or increasing circulating FFAs with a high fat diet increases mitochondria in rat skeletal muscle. The purpose of this study was to determine whether the combination of chronic chemical activation of AMPK and high fat feeding would have an additive effect on skeletal muscle mitochondria levels. We treated Wistar male rats with a high fat diet (HF), AICAR injections (AICAR), or a high fat diet and AICAR injections (HF+AICAR) for six weeks. At the end of …

Role Of Dpy-30 Proteins In Flagella, Radhika Gopal

Dissertations (1934 -)

Cilia and flagella are similar organelles found in eukaryotic cells. A microtubule-based axonemal cytoskeleton supports these organelles that project into the extracellular environment to detect various stimuli and propel fluid. These functions enable cells to sense and respond to the changing environment. Because of their importance, the fundamental mechanisms have been conserved throughout evolution. However, it remains largely unknown how axonemes are assembled and how the motility is regulated. This thesis investigated two molecules, RSP2 and RSP23, positioned in the axonemes within a T-shaped complex, the Radial Spoke (RS). Among several axonemal complexes, flagella lacking the evolutionarily conserved RS are …

Organization Of Human Sperm Chromosomes During Pronuclei Formation, Estella Jones

Theses and Dissertations in Biomedical Sciences

Chromosome organization is regarded as an important factor in regulating gene expression. In addition to the histone code, it is a part of the epigenetic mechanisms participating in fertilization and early embryonic development. Recent studies have demonstrated that chromosomes of human spermatozoa have well-defined spatial organization that includes preferred intranuclear positioning. The hypothesis of this dissertation is that sperm chromosome architecture participates in controlled transformation and activation of the paternal genome following fertilization.

Adequate model systems are necessary to study early nuclear events characteristic of human fertilization. This research focused on introduction and application of heterologous intracytoplasmic sperm injection (ICSI) …