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Vitamin D Regulates Metabolic Gene Expression, Glutamate And Glutamine Utilization, And Mitochondrial Function In Human Mammary Epithelial Cells, Sarah Beaudin
Legacy Theses & Dissertations (2009 - 2024)
Exposure to 1,25-Dihydroxyvitamin D (1,25D) decreases proliferation and induces differentiation in telomerase-immortalized human mammary epithelial (hTERT-HME1) cells. The studies described here addressed the mechanisms by which these effects are exerted. Microarray experiments were used to identify a subset of metabolic genes and pathways that are altered by 1,25D. In particular, genes involved in glutamate and glutamine utilization, including SLC1A1 and GLUL, were studied. Interestingly, qPCR analysis in a panel of six cell lines, representing either normal epithelial tissue or breast cancer, demonstrated diverse gene expression responses to 1,25D. In an isogenic model of mammary cell transformation, 1,25D altered gene expression …
Francisella Tularensis Catalase Restricts Immune Function By Impairing Trpm2 Channel Activity, Nicole Lynn Flaherty
Francisella Tularensis Catalase Restricts Immune Function By Impairing Trpm2 Channel Activity, Nicole Lynn Flaherty
Legacy Theses & Dissertations (2009 - 2024)
As an innate defense mechanism, macrophages produce reactive species that weaken pathogens and serve as secondary messengers to modify signaling responses involved in immune function. The gram-negative bacterium F. tularensis utilizes its antioxidant armature to limit the host immune response but the mechanism behind this suppression has not been defined. Here we establish that F. tularensis limits Ca2+ entry thereby limiting actin reorganization and IL-6 production in a redox-dependent fashion. Wild-type (LVS) or catalase deficient F. tularensis (∆katG) show distinct profiles in their H2O2 scavenging capacity, 1 pM/sec and 0.015 pM/sec, respectively. Murine alveolar macrophages infected with ∆katG display distinct …
Using A Novel Multiplexing Method To Track Cell Populations And Cytodifferentiation During Development Of The Submandibular Salivary Gland, Charles Thomas Manhardt
Using A Novel Multiplexing Method To Track Cell Populations And Cytodifferentiation During Development Of The Submandibular Salivary Gland, Charles Thomas Manhardt
Legacy Theses & Dissertations (2009 - 2024)
The development of submandibular salivary glands is complex and requires coordination of specific signaling events. Submandibular salivary glands originate as an epithelial invagination into the adjacent mesenchyme that leads to a single stalk and end bud; this end bud will go through a clefting process. Numerous rounds of clefting will lead to a fully developed salivary gland by this process, which is known as branching morphogenesis. As the gland undergoes morphogenesis, specific cues leading to differentiation of multiple cell types and even epithelial sub classes are required. By the later stages of development the glands are fully innervated, have an …
Vitamin D Signaling And The Impact On Mouse Mammary Gland Epithelium, Donald Grant Matthews
Vitamin D Signaling And The Impact On Mouse Mammary Gland Epithelium, Donald Grant Matthews
Legacy Theses & Dissertations (2009 - 2024)
A strong correlation between vitamin D deficiency and increased breast cancer incidence and mortality has been well established, leading researchers to further examine the possibility of using vitamin D in treatment and prevention strategies. Our long term goal is to elucidate the mechanisms by which vitamin D pathway signaling impacts on breast cancer. Generation of the high-affinity vitamin D receptor (VDR) ligand 1,25-dihydroxyvitamin D (1,25-D) from 25-hydroxyvitamin D (25-D) is mediated by CYP27B1 which is present and developmentally regulated in multiple tissues including the mammary gland. We utilized transgenic mouse models combined with diet-induced vitamin D deficiency to determine whether …