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Theses/Dissertations

2014

Cell and Developmental Biology

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Full-Text Articles in Life Sciences

Epigenetic Regulation Of Nuclear Hormone Receptor Dax-1, Michael B. Heskett Dec 2014

Epigenetic Regulation Of Nuclear Hormone Receptor Dax-1, Michael B. Heskett

Master's Theses

DAX-1 (NR0B1) is an orphan nuclear receptor that plays a key role in the development and maintenance of steroidogenic tissue in mammals. Dax-1 is also expressed in mouse embryonic stem (ES) cells and is required to maintain pluripotency. Duplication of the X-chromosome in the region containing the NR0B1 gene results in sex reversal, and mutations in NR0B1 cause adrenal hypoplasia congenita. DAX-1 has been observed to act as a corepressor of other nuclear receptors including androgen receptor (AR), estrogen receptor (ER), and steroidogenic factor 1 (SF-1). In addition to pluripotent ES cells, DAX-1 is primarily expressed in select tissues of ...


Alternative Extraction Method Of Guanidine Metabolites From Marine Sponge, Ptilocaulis Spiculifer, Savannah Barnett, Andrew A. Yeagley, Amorette Barber Dec 2014

Alternative Extraction Method Of Guanidine Metabolites From Marine Sponge, Ptilocaulis Spiculifer, Savannah Barnett, Andrew A. Yeagley, Amorette Barber

Theses, Dissertations & Honors Papers

Marine sponges are known for their use of biologically active allelopathic compounds. With almost every species of sponge having been shown to produce some chemical with medicinal properties, their survival is becoming increasingly important. Current extraction methods used by research teams require a large sample relative to the size of the sponge, which threatens the survival of the organism. 1 Ptilocaulis sp., or the orange tree sponge, is known to produce guanidine metabolites. This derivative has demonstrated biological activity against cell lines of leukemia, uterine, and cervical cancer.2 3 In this study we have developed a method for the ...


Higher-Order Unfolding Of Peri/Centric Satellite Heterochromatin Is An Early And Consistent Event In Cell Senescence: A Dissertation, Eric C. Swanson Dec 2014

Higher-Order Unfolding Of Peri/Centric Satellite Heterochromatin Is An Early And Consistent Event In Cell Senescence: A Dissertation, Eric C. Swanson

GSBS Dissertations and Theses

Cellular senescence is thought to play an essential role in many biological functions including tumor suppression and organismal aging. Senescent cells, which are permanently removed from the cell cycle, can be found both in vivo in many different tissue types and in vitro within cultures of non-immortalized cells. Despite their inability to proliferate, these cells persist and remain metabolically active for indefinite periods of time. This physiologic process occurs in response to a variety of cellular insults including oxidative stress, shortened telomeres, constitutive oncogene expression, and DNA damage, and can be initiated by upregulation of one of the two known ...


Role Of Integrin-Linked Kinase In Epidermal Integrity And Barrier Function, Samar Sayedyahossein Dec 2014

Role Of Integrin-Linked Kinase In Epidermal Integrity And Barrier Function, Samar Sayedyahossein

Electronic Thesis and Dissertation Repository

Integrin-linked kinase (ILK) is a β integrin adaptor protein that translates extracellular stimuli to intracellular signaling events. ILK plays a role in actin cytoskeleton dynamics and cell adhesion. The structure and function of the epidermis is highly dependent on cell-cell adhesion and cell-basement membrane interactions. The mechanisms whereby ILK contributes to epidermal integrity are poorly understood. Using a mouse model of epidermis-restricted Ilk gene inactivation, I observed that ILK loss causes abnormal morphology and presence of intra-epidermal and epidermal-dermal microblisters in embryos as early as E17.5. ILK-deficient epidermis is also characterized by abnormal localization or/and absence of adherens ...


Arabidopsis Chromatin Remodeler Brahma: Its Functional Interplay With Polycomb Proteins And The Ref6 Histone Demethylase, Chenlong Li Dec 2014

Arabidopsis Chromatin Remodeler Brahma: Its Functional Interplay With Polycomb Proteins And The Ref6 Histone Demethylase, Chenlong Li

Electronic Thesis and Dissertation Repository

BRAHMA (BRM) is a SWI/SNF-type chromatin remodeling ATPase that plays an important role in regulation of gene expression. Tri-methylation of lysine 27 on histone H3 (H3K27me3) is a histone modification that is associated with transcriptionally repressed genes and catalyzed by Polycomb Group (PcG) proteins. BRM has been proposed to antagonize the function of PcG proteins but the underlying molecular mechanism is unclear. To understand how BRM regulates the function of PcG proteins during plant development, a genome-wide analysis of H3K27me3 in brm mutant was performed using chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq). Loss of BRM leads to ...


Understanding The Meiotic Roles Of Sisters Unbound In Drosophila Melanogaster, Badri Krishnan Dec 2014

Understanding The Meiotic Roles Of Sisters Unbound In Drosophila Melanogaster, Badri Krishnan

Doctoral Dissertations

During meiosis, cohesin is required for sister chromatid cohesion and for formation of chromosome cores. Multiple processes including chromosome segregation, recombination and synaptonemal complex (SC) are dependent on cohesin. Cohesin complex consists of two SMC subunits- SMC1, SMC3 and two non-SMC subunits RAD21/REC8 in meiosis and SA. But in Drosophila, non-SMC subunits have not been shown to be required for cohesion. We have identified a gene sisters unbound, which along with previously identified ord and solo, form a group of three genes (sos) which do not have any sequence similarity to cohesins but performs functions demonstrated by cohesins.

Proper ...


The Role Of Nag-1 In Tumorigenesis, Kyung-Won Min Dec 2014

The Role Of Nag-1 In Tumorigenesis, Kyung-Won Min

Doctoral Dissertations

This dissertation explores the nature of a divergent member of the Transforming Growth Factor-β [beta] superfamily, the non-steroidal anti-inflammatory drugs activated gene (NAG-1), as it relates to its regulation and biological activity in cancer context. Our lab has extensively studied on the molecular mechanism by which phytochemicals and NSAIDs induce apoptosis correlation with NAG-1 expression in human colorectal cancer (CRC) cells. Significant data from in vitro studies suggest that NAG-1 has an anti-tumorigenic activity which elicits apoptosis in a cyclooxygenase (COX)-independent manner in CRC cells. Indeed, NAG-1 transgenic mice developed less aberrant polyp foci (APC) compared to those of ...


Reverse Genetics Approach To Examine Myosin Xi Functions In Pollen Tube Growth, Stephanie Lin Madison Dec 2014

Reverse Genetics Approach To Examine Myosin Xi Functions In Pollen Tube Growth, Stephanie Lin Madison

Doctoral Dissertations

Pollen tube growth is an essential aspect of plant reproduction because it is the mechanism through which non-motile sperm cells are delivered to ovules thus allowing fertilization to occur. A pollen tube is a single cell that only grows at the tip, and this tip growth depends on actin filaments. Plants encode class VIII and class XI myosins as actin-based motor proteins, of which class XI myosins are required for cell expansion in vegetative tissues.

In Arabidopsis thaliana, 6 of 13 myosin XI genes are expressed in pollen: XIA, XIB, XIC, XID, XIE, and XIJ. Initially, two artificial microRNA constructs ...


Investigation Of Nuclear And Cytoplasmic Functions Of The Dlipin Protein Of Drosophila Melanogaster, Qiuyu Chen Dec 2014

Investigation Of Nuclear And Cytoplasmic Functions Of The Dlipin Protein Of Drosophila Melanogaster, Qiuyu Chen

Theses and Dissertations

Lipin family proteins are highly conserved proteins present in species ranging from mammals to yeast. Lipin 1, the first Lipin gene identified in fatty liver dystrophy (fld) mutant mice, encodes the bifunctional protein Lipin 1, which can serve as an Mg2+-dependent phosphatidic acid phosphatase (PAP) and transcriptional co-regulator. dLipin, the single Lipin ortholog of Drosophila melanogaster, is required in triglyceride synthesis and fat body development. To study the transcriptional co-regulator activity of dLipin, nuclear receptors were screened to find receptors that interact with dLipin. The genetic interaction data indicated that Drosophila hepatic nuclear receptor 4 (HNF4) was a promising ...


Characterization Of Histidine Decarboxylase In Drosophila Using An Internal Flag Epitope, Maxwell Mianecki Dec 2014

Characterization Of Histidine Decarboxylase In Drosophila Using An Internal Flag Epitope, Maxwell Mianecki

Masters Theses

Histamine is a neurotransmitter in arthropods and is responsible for synaptic transmission in vision, mechanosensation, temperature sensing and sleep cycle in Drosophila. Histamine is synthesized by the enzyme histidine decarboxylase (HDC). While histamine is detectable within tissues using current immunofluorescent labeling techniques, immunological approaches have not been successful for HDC itself, with both direct antibodies and terminal epitope tags determined to be ineffective. In order to avoid loss of the epitope tag through putative N-­‐ and C-­‐terminal proteolytic cleavage, known to occur for HDC in other organisms, an internal epitope tag that does not disrupt enzyme function was utilized ...


The Drosophila T-Box Transcription Factor Midline Functions Within The Insulin/Akt And C-Jun-N-Terminal Kinase Signaling Pathways To Regulate Interomatidial Bristle Formation And Cell Survival, Qichuan Chen Dec 2014

The Drosophila T-Box Transcription Factor Midline Functions Within The Insulin/Akt And C-Jun-N-Terminal Kinase Signaling Pathways To Regulate Interomatidial Bristle Formation And Cell Survival, Qichuan Chen

Master's Theses

From a genetic and allelic modifier screen, we report that the Drosophila melanogaster T-box transcription factor midline (mid), a homolog to the human TBX20 gene, interacts with dFOXO within the insulin receptor (InR) and the c-Jun-N-terminal kinase (JNK) signaling pathways to regulate interommatidial bristle (IOB) formation. Previous studies have identified mid’s role in cell fate specification of sensory organ precursor cells in conjunction with the Notch-Delta signaling pathway (Das et al., 2013). The Notch, InR, and JNK signaling pathways regulate dFOXO activity under conditions of stress. Thus, we determined the effects of oxidative stress and metabolic stress by exposing ...


Evaluating The Effects Of Aroclor 1260 In Non-Alcoholic Fatty Liver Disease : The Role Of Xenobiotic Receptors., Banrida Wahlang Dec 2014

Evaluating The Effects Of Aroclor 1260 In Non-Alcoholic Fatty Liver Disease : The Role Of Xenobiotic Receptors., Banrida Wahlang

Electronic Theses and Dissertations

Polychlorinated biphenyls (PCBs) are persistent environmental toxicants, present in 100% of US adults and dose-dependently associated with nonalcoholic fatty liver disease (NAFLD) in epidemiologic studies. PCBs are predicted to interact with receptors previously implicated in xenobiotic/energy metabolism and NAFLD. These receptors include the aryl hydrocarbon receptor (AhR), pregnane xenobiotic receptor (PXR), constitutive androstane receptor (CAR), peroxisome proliferator-activated receptors (PPARs), liver-X-receptor and farnesoid-X-receptor. This study evaluated the hepatic effects of the PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity. Male C57Bl/6J mice were fed a control or 42% high fat ...


Induction Of Differentiation Of Dental Pulp-Derived Mesenchymal Stem Cells (Dpsc), Aubrey Young Dec 2014

Induction Of Differentiation Of Dental Pulp-Derived Mesenchymal Stem Cells (Dpsc), Aubrey Young

UNLV Theses, Dissertations, Professional Papers, and Capstones

Mesenchymal stem cells are derived from a variety of human tissues and are being bioengineered and studied for possible uses in the advancement of medicine. Recent efforts are being focused on Dental Pulp Stem Cells (DPSC's) due to the accessibility of this tissue. Many factors influence DPSC quality and quantity, including the specific methods used to isolate, collect, concentrate, and store these isolates once they are removed. Ancillary factors, such as the choice of media, the selection of early versus late passage cells, and cryopreservation techniques may also influence the differentiation potential and proliferative capacity of DPSC isolates.

The ...


The Role Of Stem Cells In Adipose Tissue Remodeling., Candice Reshay Holden 1988- Dec 2014

The Role Of Stem Cells In Adipose Tissue Remodeling., Candice Reshay Holden 1988-

Electronic Theses and Dissertations

The work presented in this dissertation outlines the role of stem cells in the remodeling of adipose tissue under conditions of nutrient excess. Obesity-induced variations in adipose tissue stem cell distribution were uncovered by analysis of the stromal vascular fraction isolated from mice fed a high fat diet for several weeks. Bone marrow cell transplantation was used to determine the derivation of progenitor cells found in adipose tissue; and supplementation of depleted progenitor cell populations achieved via direct cell transplantation, helped to determine the contribution of these progenitor cells to the remodeling process. The dissertation is presented in five chapters ...


Lkb1 Deficient Non-Small Cell Lung Cancer Cells Are Vulnerable To Energy Stress Induced By Atp Depletion, Chao Yang Dec 2014

Lkb1 Deficient Non-Small Cell Lung Cancer Cells Are Vulnerable To Energy Stress Induced By Atp Depletion, Chao Yang

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Lung cancer is the second most frequent cancer in United States, which represents about 13.5% of new cancer cases every year. It accounts for about 27.2% of all cancer related deaths, which is more than the sum of deaths caused by prancretic, breast and colorectal. On average, only about 16% of lung cancer patients survive beyond 5 years. LKB1 is the third most mutated gene in lung cancer. It has been shown that LKB1 is mutated in at least 15% to 30% of NSCLC. Tumor with LKB1 mutation is associated with poor differentiation, high metastasis and worse response ...


Sox2-Dependent Transcriptional Control Of Airway Differentiation In The Mouse Lung, Belinda J. Hernandez Dec 2014

Sox2-Dependent Transcriptional Control Of Airway Differentiation In The Mouse Lung, Belinda J. Hernandez

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

The lung is a highly branched tree-like tubular system that results from more than 20 generations of the conducting airways and consists of 300 million alveoli for gas exchange. Airway branches form via branching morphogenesis and then mature into conducting airways, in which the number and distribution of different cell types need to be precisely controlled. The conducting airways contain four lung cell types: club cells, ciliated cells, basal cells, and neuroendocrine cells.SOX2 is a well-known conducting airway marker. SOX2 is a transcription factor that is known to be important in embryonic development and induction of pluripotent stem cells ...


P120-Catenin Regulates Rest And Corest, And Modulates Mouse Embryonic Stem Cell Differentiation, Moonsup Lee Dec 2014

P120-Catenin Regulates Rest And Corest, And Modulates Mouse Embryonic Stem Cell Differentiation, Moonsup Lee

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

The canonical-Wnt pathway and beta-catenin have been extensively studied to determine their contributions to stem cell biology, but less is known about p120-catenin in the nuclear compartment. P120 is developmentally required as a consequence of its biochemical and functional interactions with cadherins, small-GTPases and transcriptional regulators. We report here that p120-catenin binds to and negatively regulates REST and CoREST, that others have indicated form a repressive complex having diverse key roles in developmental and pathologic gene regulation. We thus provide the first evidence for a direct upstream modulator of REST/CoREST function. Using mouse embryonic stem cells (mESCs), mammalian cell ...


Novel Posttranslational Modification In Lkb1 Activation And Function, Szu-Wei Lee Dec 2014

Novel Posttranslational Modification In Lkb1 Activation And Function, Szu-Wei Lee

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Cancer cells display dramatic alterations in cellular metabolism to meet their needs of increased growth and proliferation. In the last decade, cancer research has brought these pathways into focus, and one emerging issue that has come to attention is that many oncogenes and tumor-suppressors are intimately linked to metabolic regulation (Jones and Thompson, 2009). One of the key tumor-suppressors involved in metabolism is Liver Kinase B1 (LKB1). LKB1 is the major upstream kinase of the evolutionarily conserved metabolic sensor—AMP-activated protein kinase (AMPK). Activation of the LKB1/AMPK pathway provides a survival advantage for cells under energy stress. LKB1 forms ...


Role Of Phosphorylation Of Focal Adhesion Kinase At Tyrosine 861 In Prostate Cancer Metastasis, Tanushree Chatterji Dec 2014

Role Of Phosphorylation Of Focal Adhesion Kinase At Tyrosine 861 In Prostate Cancer Metastasis, Tanushree Chatterji

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that mediates interactions between the extracellular matrix and intracellular signaling pathways critical in promoting numerous cellular functions including adhesion, proliferation, survival and migration. Most FAK functions result from phosphorylation by Src family kinases, which trigger numerous signaling cascades. Overexpression of FAK is associated with metastasis in many solid tumors, including prostate cancer. Hence, understanding the mechanisms by which FAK is regulated in prostate cancer will better elucidate its role in prostate cancer metastasis. Work in this dissertation tested the hypothesis that altered phosphorylation of FAK is critical for cell migration and ...


Sustained Adrenergic Signaling Promotes Cervical Cancer Progression, Nouara C. Sadaoui Dec 2014

Sustained Adrenergic Signaling Promotes Cervical Cancer Progression, Nouara C. Sadaoui

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Background: Chronic stress and sustained adrenergic signaling are known to promote tumor progression. The underlying mechanisms behind this process are not well understood. We examined the effects of sustained adrenergic signaling on cervical cancer progression through increased expression of HPV oncogenes, E6 and E7.

Materials and Methods: ADRβ expression levels were examined in patient-derived cervical cancer samples. We used an orthotopic model of cervical cancer to investigate the effects of restraint stress on tumor growth and metastasis. We evaluated the in vivo effects of a β-blocker, propranolol, and HPV E6/E7 siRNA. In vitro, ADRβ positive cervical cancer cells were ...


Mdm2-Mediated Degradation Of Sirt6 Phosphorylated By Akt1 Promotes Tumorigenesis And Trastuzumab Resistance In Breast Cancer, Umadevi Thirumurthi Dec 2014

Mdm2-Mediated Degradation Of Sirt6 Phosphorylated By Akt1 Promotes Tumorigenesis And Trastuzumab Resistance In Breast Cancer, Umadevi Thirumurthi

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Sirtuin6 (SIRT6) is one of the members of the Sirtuin family and functions as a longevity assurance gene by promoting genomic stability. It also regulates various cancer-associated pathways and was recently established as a bonafide tumor suppressor in colon cancer. This suggests that SIRT6 is an attractive target for pharmacological activation in cancer treatment, and hence, identification of potential regulators of SIRT6 would be an important and critical contribution towards cancer treatment. Here, we show that AKT1 phosphorylates SIRT6 at Ser338 and induces MDM2-SIRT6 interaction, priming SIRT6 for degradation via the MDM2-dependent ubiquitin-proteasome pathway. Blocking SIRT6 Ser338 phosphorylation ...


Epidermal Growth Factor Receptor Induces Fyn Expression Via Up-Regulation Of P47phox In Glioblastoma Multiforme, Blake P. Johnson Dec 2014

Epidermal Growth Factor Receptor Induces Fyn Expression Via Up-Regulation Of P47phox In Glioblastoma Multiforme, Blake P. Johnson

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Src family kinases (SFKs) are commonly over-expressed and/or activated in glioblastoma multiforme (GBM), where they serve as key mediators of GBM cell proliferation, survival, invasion and angiogenesis. Mechanisms of allosteric SFK activation are well described; however, the SFK Fyn is commonly up-regulated at the mRNA level in multiple human cancers, including GBM, where the mode of increased expression is poorly understood. Since activating mutations in the epidermal growth factor receptor (EGFR) are commonly occurring in GBM, we examined whether EGFR could induce Fyn expression. Here, we found that wild-type EGFR, and to a greater extent hyper-activating EGFR mutants, EGFRΔIII ...


Jab1 Negatively Regulates Pten And Promotes Resistance To Trastuzumab In Her2-Positive Breast Cancer, Thuy T. Vu Dec 2014

Jab1 Negatively Regulates Pten And Promotes Resistance To Trastuzumab In Her2-Positive Breast Cancer, Thuy T. Vu

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

HER2-positive breast cancer, which is characterized by the over-expression of the HER2 onco-protein, accounts for approximately 20% of all breast cancer cases. Trastuzumab (Herceptin), the first targeted therapy approved for HER2-positive disease, potently prevents the activation of signaling pathways downstream of HER2 and significantly improves patients’ outcomes. However, resistance to trastuzumab is inevitable; such resistance can occur through reduced expression of PTEN protein.

Jab1 is over-expressed in 50% of primary cancers and 90% of metastatic tumors. Our lab previously showed that depletion of Jab1 in combination with trastuzumab treatment up-regulated PTEN in mouse xenografts refractory to trastuzumab. PTEN was not ...


Targeting Cox-2 And Rank In Aggressive Breast Cancers: Inflammatory Breast Cancer And Triple-Negative Breast Cancer, Monica Elizabeth Reyes Dec 2014

Targeting Cox-2 And Rank In Aggressive Breast Cancers: Inflammatory Breast Cancer And Triple-Negative Breast Cancer, Monica Elizabeth Reyes

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Inflammatory breast cancer (IBC) and triple-negative breast cancer (TNBC) are two highly aggressive breast cancer subtypes associated with a poor outcome. Despite sensitivity to current treatment, these breast cancers subtypes have a high recurrence rate and proclivity to metastasize early. The aggressiveness of IBC and TNBC have been linked to CSCs and epithelial to mesenchymal transition (EMT), which are critical features of breast cancer progression and metastasis. The clinical challenge faced in the treatment of IBC and TNBC is finding a treatment strategy to target the cancer stem-like (CSC) population to block metastasis. Cyclooxygenase-2 (COX-2) and receptor activator of nuclear ...


Extent Of Cysteine Modification Of Snap-25 In Vitro, Alex Mcgregor Dabell Dec 2014

Extent Of Cysteine Modification Of Snap-25 In Vitro, Alex Mcgregor Dabell

Theses and Dissertations

Exocytosis, the fusion of a vesicle to a cellular membrane, involves a protein named SNAP-25. This protein, containing two alpha helices connected with a linker region, is localized to the cell membrane via palmitic acids attached to the cysteine residues of its linker region in a process called palmitoylation. Are cysteine residues of the SNAP-25 linker region palmitoylated in an ordered manner and to a particular extent? The answer to this question may give insight into the regulated nature of exocytosis. While it is generally accepted that SNAP-25 must be palmitoylated in order to perform its exocytotic functions, the details ...


Alcohol Modulation Of Dopamine Release, Nathan Dan Schilaty Dec 2014

Alcohol Modulation Of Dopamine Release, Nathan Dan Schilaty

Theses and Dissertations

The mesolimbic dopamine (DA) system projects from the ventral tegmental area (VTA) to structures associated with the limbic system, primarily the nucleus accumbens (NAc). This system has been implicated in the rewarding effects of drugs of abuse. Many drugs of abuse act in the VTA, the NAc, or both. Dopamine neurons in the VTA that project to the NAc, and the GABA neurons that inhibit DA neurons locally in the VTA or project to the NAc, play an important role in mediating addiction to various drugs of abuse, in particular alcohol. There is a growing body of evidence of co-dependence ...


The Use Of Surface Cytokines As Biomarkers In B Cell Mediated Autoimmune Diseases, Abby Jones Weldon Dec 2014

The Use Of Surface Cytokines As Biomarkers In B Cell Mediated Autoimmune Diseases, Abby Jones Weldon

Loma Linda University Electronic Theses, Dissertations & Projects

RA and SLE are B cell-mediated autoimmune diseases dominated by autoantibodies that affect over 1.5 million Americans. Together RA and SLE contribute to over 29 billion in healthcare costs, therefore due to the high financial burden and physical toll of these diseases on the population, there is a critical need to effectively and efficiently diagnose and treat RA and SLE patients. The aim of our studies was to identify biomarkers and drug targets to improve the identification and treatment of RA and SLE patients. As discussed above, APRIL, BAFF and TSLP have been implicated in the pathogenesis of RA ...


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 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 ...