{"id":82,"date":"2017-11-07T16:09:04","date_gmt":"2017-11-07T21:09:04","guid":{"rendered":"https:\/\/my.dev.vanderbilt.edu\/coverlab\/?page_id=82"},"modified":"2019-08-01T12:20:52","modified_gmt":"2019-08-01T17:20:52","slug":"our-research","status":"publish","type":"page","link":"https:\/\/my.dev.vanderbilt.edu\/coverlab\/our-research\/","title":{"rendered":"Our Research"},"content":{"rendered":"

Helicobacter pylori <\/i><\/b><\/span><\/span>and gastric cancer.<\/b><\/span><\/span>\u00a0<\/span>Gastric cancer is a leading cause of cancer-related death worldwide, and\u00a0<\/span>H. pylori<\/i><\/span>\u00a0infection is the strongest known risk factor for this malignancy.\u00a0<\/span>H.\u00a0pylori<\/i><\/span>\u00a0exhibits a high level of intraspecies genetic diversity, and several strain-specific features of\u00a0<\/span>H.\u00a0pylori<\/i><\/span>\u00a0are linked to development of gastric cancer. These include the presence of a 40-kb chromosomal region known as the\u00a0<\/span>cag<\/i><\/span>\u00a0pathogenicity island (PAI), secretion of active forms of a toxin (VacA), and the production of certain strain-specific outer membrane protein adhesins. We study the activities of these strain-specific factors in cell culture and animal models. We also seek to develop improved methods for identifying\u00a0<\/span>H. pylori<\/i><\/span>-infected individuals who have the highest risk of gastric cancer, so they can be targeted for therapeutic intervention.\u00a0<\/span><\/span><\/p>\n

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\"Elife<\/p>\n<\/div>\n

H. pylori cag<\/i><\/b><\/span><\/span>\u00a0type IV secretion system.<\/b><\/span><\/span>\u00a0A 40-kb chromosomal region known as the\u00a0<\/span><\/span>cag<\/i><\/span><\/span>\u00a0pathogenicity island is present in some\u00a0<\/span><\/span>H. pylori<\/i><\/span><\/span>\u00a0strains but not others. This pathogenicity island encodes an effector protein (CagA) that is delivered into gastric epithelial cells, as well as a type IV secretion system that mediates CagA secretion. CagA causes alterations in host cell signaling and has been designated as a bacterial oncoprotein. We are conducting studies to understand the assembly, molecular architecture, and functional properties of the\u00a0<\/span><\/span>cag<\/i><\/span><\/span>\u00a0type IV secretion system.<\/span><\/span><\/span><\/div>\n
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\"vacA_opt<\/i><\/b><\/span><\/span><\/span><\/div>\n<\/div>\n
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H. pylori<\/em> VacA toxin.<\/strong>\u00a0 VacA is a\u00a0secreted channel-forming toxin unrelated to other known bacterial toxins. Most\u00a0H. pylor i<\/em>strains contain a\u00a0vacA<\/em>\u00a0gene, but there is marked variation among strains in\u00a0VacA\u00a0toxin activity. This variation is attributable to strain-specific variations in\u00a0VacA\u00a0amino acid sequences, as well as variations in the levels of\u00a0VacA\u00a0transcription and secretion. The most extensively studied\u00a0VacA\u00a0activity is its capacity to stimulate intracellular vacuole formation, but the toxin has many additional effects on host cells. Multiple cell types are susceptible to\u00a0VacA, including gastric epithelial cells, parietal cells, and several types of immune cells. We are conducting studies to understand VacA structure-function relationships and develop a better understanding of the mechanisms by which VacA causes alterations in host cells. In addition, we seek to understand how immunomodulatory actions of VacA influence\u00a0H. pylori<\/em>-host interactions in vivo.<\/span><\/span><\/span><\/div>\n<\/div>\n
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\"abx_opt\"<\/p>\n<\/div>\n

H. pylori<\/i><\/b><\/span><\/span>\u00a0outer membrane proteins.<\/b><\/span><\/span>\u00a0<\/span><\/span>H. pylori<\/i><\/span><\/span>\u00a0outer membrane proteins have important roles in bacteria-host cell interactions. We seek to understand the roles of individual outer membrane proteins in bacterial adherence to gastric epithelial cells and colonization of the stomach in animal models.\u00a0<\/span><\/span><\/span><\/div>\n
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\"interplay\"<\/span><\/span><\/span><\/div>\n
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Dietary composition as a determinant of gastric cancer risk.<\/b><\/span><\/span>\u00a0Epidemiologic studies have shown that a high salt diet is a risk factor for gastric cancer. We are conducting studies to understand how\u00a0<\/span><\/span>H. pylori<\/i><\/span><\/span>\u00a0gene expression is regulated in response to high salt environmental conditions. In addition, we are analyzing the effects of a high salt diet in animal models of\u00a0<\/span><\/span>H. pylori<\/i><\/span><\/span>\u00a0infection.\u00a0<\/span><\/span><\/span><\/div>\n
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\"GENERAL_opt\"<\/p>\n<\/div>\n

Geographic variation in gastric cancer risk.<\/b><\/span>\u00a0The incidence of gastric cancer varies markedly throughout the world. Similarly, there is marked geographic variation in genetic features of\u00a0<\/span>H. pylori.<\/i><\/span>\u00a0We hypothesize that the geographic variation in gastric incidence is attributable at least in part to geographic variation in\u00a0<\/span>H. pylori<\/i><\/span>\u00a0virulence. We are conducting comparative genomic studies to analyze\u00a0<\/span>H. pylori<\/i><\/span>\u00a0strains from multiple parts of the world and determine how geographic variation among\u00a0<\/span>H. pylori<\/i><\/span>\u00a0strains may impact gastric cancer risk.\u00a0<\/span><\/span><\/div>\n
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Helicobacter pylori and gastric cancer.\u00a0Gastric cancer is a leading cause of cancer-related death worldwide, and\u00a0H. pylori\u00a0infection is the strongest known risk factor for this malignancy.\u00a0H.\u00a0pylori\u00a0exhibits a high level of intraspecies genetic diversity, and several strain-specific features of\u00a0H.\u00a0pylori\u00a0are linked to development … Continue reading →<\/span><\/a><\/p>\n","protected":false},"author":7191,"featured_media":0,"parent":0,"menu_order":2,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-82","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/my.dev.vanderbilt.edu\/coverlab\/wp-json\/wp\/v2\/pages\/82","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/my.dev.vanderbilt.edu\/coverlab\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/my.dev.vanderbilt.edu\/coverlab\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/my.dev.vanderbilt.edu\/coverlab\/wp-json\/wp\/v2\/users\/7191"}],"replies":[{"embeddable":true,"href":"https:\/\/my.dev.vanderbilt.edu\/coverlab\/wp-json\/wp\/v2\/comments?post=82"}],"version-history":[{"count":48,"href":"https:\/\/my.dev.vanderbilt.edu\/coverlab\/wp-json\/wp\/v2\/pages\/82\/revisions"}],"predecessor-version":[{"id":739,"href":"https:\/\/my.dev.vanderbilt.edu\/coverlab\/wp-json\/wp\/v2\/pages\/82\/revisions\/739"}],"wp:attachment":[{"href":"https:\/\/my.dev.vanderbilt.edu\/coverlab\/wp-json\/wp\/v2\/media?parent=82"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}