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Articles 1 - 12 of 12

Full-Text Articles in Cell Biology

Traf2 Phosphorylation Regulates Cd40 Signaling To Facilitate B-Cell Lymphoma Progression, Lauren Michelle Workman Dec 2014

Traf2 Phosphorylation Regulates Cd40 Signaling To Facilitate B-Cell Lymphoma Progression, Lauren Michelle Workman

Theses and Dissertations

CD40 is a TNF-Receptor (TNFR) superfamily member that functions to promote several facets of the humoral immune response--including B cell proliferation, differentiation, antibody isotype switching, and cytokine expression. TNFR superfamily members lack intrinsic kinase activity and must recruit members of the TNFR-associated factor (TRAF) family of adaptor proteins to connect the receptor to intracellular signaling pathways. CD40-mediated JNK and NF-κB activation is critical for an intact humoral immune response; however, the precise mechanisms governing the spatiotemporal activation of these pathways are not completely understood.

In this study we report that CD40 ligation results in the dual phosphorylation of TRAF2 on ...


The Role Of Neuronal Mtorc1 Signaling In The Regulation Of Physiological Processes, Kenjiro Muta Dec 2014

The Role Of Neuronal Mtorc1 Signaling In The Regulation Of Physiological Processes, Kenjiro Muta

Theses and Dissertations

The mammalian target of rapamycin complex 1 (mTORC1) is an evolutionary conserved serine/threonine kinase regulating diverse cellular functions, including cell growth, protein synthesis and sensing nutrients and energy status. Prior studies have identified the involvement of hypothalamic mTORC1 in the control of energy balance, renal sympathetic activation and blood pressure regulation.

Hypothalamic insulin receptor signaling through the phosphatidylinositol 3-kinase (PI3K) is known to regulate energy homeostasis and sympathetic nerve activity (SNA). We examined the role of hypothalamic mTORC1 in the anorectic and sympathetic effects of central insulin. mTORC1 inhibition by rapamycin or PI3K mutation resulted in blunted regional SNA ...


Molecular And Cellular Basis Of Hematopoietic Stem Cells Maintenance And Differentiation, Khanh Linh Duong Dec 2014

Molecular And Cellular Basis Of Hematopoietic Stem Cells Maintenance And Differentiation, Khanh Linh Duong

Theses and Dissertations

The blood system consists of two main lineages: myeloid and lymphoid. The myeloid system consists of cells that are part of the innate immune response while the lymphoid system consist of cells that are part of humoral response. These responses protect our bodies from foreign pathogens. Thus, malignancies in these systems often cause complications and mortality. Scientists world wide have been researching alternatives to treat hematologic disorders and have explored induced pluripotent stem cells (iPSCs) and the conversion of one cell type to another.

First, iPS cells were generated by overexpression of four transcription factors: Oct4, Sox2, Klf4 an cMyc ...


Manipulation Of The Innate Immune Response And Evasion Of Macrophage Host Defense Mechanisms By Francisella Tularensis, Matthew Eugene Long Dec 2014

Manipulation Of The Innate Immune Response And Evasion Of Macrophage Host Defense Mechanisms By Francisella Tularensis, Matthew Eugene Long

Theses and Dissertations

Tularemia is a potentially fatally illness caused by the facultative intracellular Gram-negative bacterium Francisella tularensis. Virulent strains of F. tularensis can cause a fatal disease after inhalation of a few as ten organisms. Due to the highly pathogenic features of Francisella, it has been designated as a Tier 1 select agent, meaning that its possession and handling is highly restricted. Macrophages are phagocytes that play a central role in the innate immune response to infection that can be used by certain pathogens, including Francisella, as a niche for bacterial replication and dissemination during infection. After infection of macrophages Francisella escapes ...


The Role Of Aim2 And Nlrp12 In The Innate Immune Response To Francisella Tularensis, Tyler Kent Ulland Dec 2014

The Role Of Aim2 And Nlrp12 In The Innate Immune Response To Francisella Tularensis, Tyler Kent Ulland

Theses and Dissertations

The innate immune response to pathogens by the host is dependent upon the interplay of both pathogen and host intrinsic factors. Nucleotide-binding domain leucine-rich repeat containing (NLR) and pyrin and HIN200 domain containing (PYHIN) proteins are intracellular sensors of damage-associated and pathogen-associated molecular patterns. The studies presented here focus on the PYHIN molecule, AIM2, and the NLR, NLRP12, and the importance of bacteria- and host-associated proteins in the coordination of the innate immune response to the Gram-negative pathogen Fracisella tularensis. We have found that several genes expressed by F. tularensis encode for proteins that, when disrupted, cause the bacteria to ...


Regulation Of Protein Trafficking By Ral Gtpases And Exocyst In Epithelial Cells, Yu-Tsan Liu Jul 2014

Regulation Of Protein Trafficking By Ral Gtpases And Exocyst In Epithelial Cells, Yu-Tsan Liu

Theses and Dissertations

In polarized epithelial cells, vectorial protein trafficking is important for transporting specific membrane proteins to generate distinct apical and basolateral membrane protein compositions. The Exocyst is a conserved hetero-octameric protein complex, which regulates different aspects of protein trafficking, including tethering of the Golgi-derived vesicles to target membranes. Two of the Exocyst subunits, Sec5 and Exo84, competitively bind to the small GTPases, RalA and RalB, in a GTP-dependent manner. Although Ral GTPases have been proposed to mediate assembly of Exocyst holocomplexes, we hypothesize that they actually serve to allosterically regulate Exocyst functions by promoting association or disassociation of additional factors. Previous ...


Prostaglandin Signaling Temporally Regulates Actin Cytoskeletal Remodeling During Drosophila Oogenesis, Andrew James Spracklen Jul 2014

Prostaglandin Signaling Temporally Regulates Actin Cytoskeletal Remodeling During Drosophila Oogenesis, Andrew James Spracklen

Theses and Dissertations

Prostaglandins (PGs) are small, lipid signaling molecules produced downstream of cyclooxygenase (COX) enzymes. PG signaling regulates many processes including pain, inflammation, fertility, cardiovascular function and disease, and cancer. One mechanism by which PG signaling exerts its function is by regulating the dynamics of the actin cytoskeleton; however, the exact mechanisms remain largely undefined.

Drosophila oogenesis provides an ideal system to determine how PG signaling regulates the actin cytoskeleton. Drosophila follicles, or eggs, pass through 14 well- characterized, morphologically defined stages of development. Each developing follicle is comprised of 16 interconnected germline-derived cells (15 nurse cells and 1 oocyte) that are ...


Intrinsic And Extrinsic Regulation Of Dna Methylation During Malignant Transformation, Bo-Kuan Wu Jul 2014

Intrinsic And Extrinsic Regulation Of Dna Methylation During Malignant Transformation, Bo-Kuan Wu

Theses and Dissertations

Cytosine methylation of CpG dinucleotides is an epigenetic modification that cells use to regulate gene expression, largely to promote transcriptional silencing. Focal hypermethylation of tumor suppressor genes (TSGs) accompanied by genomic hypomethylation are epigenetic hallmarks of malignancy. DNA methyltransferase 1 (DNMT1) is the principle vertebrate enzyme responsible for maintenance of DNA methylation and its dysregulation has been found to lead to aberrant methylation in cancer. In addition, recent findings demonstrated that the ten-eleven translocation 1 (TET1) protein functions as a 5-methylcytosine dioxygenase that converts 5-methylcytosine (5mC) bases to 5-hydroxymethylcytosine (5hmC) to mediate active DNA demethylation. Emerging evidence suggests that TET1 ...


Oncomorphic Tp53 Mutations In Advanced Serous Ovarian Carcinomas, Pavla Brachova May 2014

Oncomorphic Tp53 Mutations In Advanced Serous Ovarian Carcinomas, Pavla Brachova

Theses and Dissertations

The tumor suppressor gene TP53 sits at the crux of response to cellular stresses. This is the most frequently inactivated gene in human tumors, being the target of somatic mutations. The protein product of TP53 is p53, and plays a crucial role in anti-proliferative signals through the induction of apoptosis, senescence, and cell-cycle arrest when activated by stresses such as genotoxic chemotherapeutic drugs. Therefore, the status of TP53 mutation in a tumor has profound implications for the tumorigenic potential as well as the response to anti-cancer therapies. Indeed, numerous studies have shown a predictive and prognostic value of TP53 mutations ...


Use Of Zebrafish To Test Candidate Genes And Mutations Associated With Structural Birth Defects, Primarily In Cleft Lip And Palate, Tiffany Lynn Smith May 2014

Use Of Zebrafish To Test Candidate Genes And Mutations Associated With Structural Birth Defects, Primarily In Cleft Lip And Palate, Tiffany Lynn Smith

Theses and Dissertations

Cleft lip and/or palate (CL/P) is a group of congenital birth defect caused by the failure of the lip and/or palate to properly fuse during facial development. This defect occurs in approximately 1:700 live births and is the most second most common developmental defect. Twin studies and evaluation of family history reveals that risk for CL/P is influenced by genetics. However, to date less than half of the heritable risk for CL/P has been ascribed to specific genes.

To identify new genes involved in CL/P, our colleagues, Dr. Manak and Dr. Murray, screened ...


Neutrophil Priming And Host Inflammation: The Roles Of Nox2 And Toll-Like Receptors, Laura Christine Whitmore May 2014

Neutrophil Priming And Host Inflammation: The Roles Of Nox2 And Toll-Like Receptors, Laura Christine Whitmore

Theses and Dissertations

Neutrophils, essential innate immune cells, recognize danger signals through receptors on their surface. Upon receptor ligation, neutrophils may undergo priming, a process involving limited reactive oxygen species (ROS) generation and partial degranulation. Priming facilitates neutrophil migration and prepares the cell for an enhanced response to a secondary stimulus, including a spike in ROS generation by NADPH oxidase 2 (NOX2). It is well established that NOX2-derived oxidants are involved in pathogen killing and that off-target effects can cause host tissue damage; however, several lines of recent evidence also support an anti-inflammatory function for NOX2 oxidants. First, patients with chronic granulomatous disease ...


Characterization Of Mir-888 Expression And Regulation In Endometrial Cancer, Adriann Marie Hovey May 2014

Characterization Of Mir-888 Expression And Regulation In Endometrial Cancer, Adriann Marie Hovey

Theses and Dissertations

Endometrial cancer is the fourth most common cancer in women and the most common gynecological malignancy. While patient outcome has improved for the majority of cancers, the outlook for endometrial cancer has steadily decreased. In order to address this problem, we must better understand the different mechanisms involved in endometrial cancer development and progression. To this end, we quantified expression of 667 miRNAs in four endometrioid adenocarcinoma and four serous adenocarcinoma using Taqman Low Density Arrays (TLDAs). miR-888 was one of the most highly overexpressed miRNAs in both endometrial cancer subtypes. Analysis of miR-888 expression across multiple cancer types using ...