The Proteomics Core (Core B) provides state-of-the-art instrumentation, methodology, and expertise in proteomics to investigators in this PPG. A unique feature of the Proteomics Core is the availability of cutting? edge quantitative proteomics analysis technologies that allows high sensitivity measurements of proteome changes in models of gastric cancer. The Proteomics Core provides 1) identification of proteins in complex samples, 2) quantitative analyses of differential protein expression from in vitro and in vivo samples, and 3) global analyses of protein modifications. Proteomics Core staff provides consultation on experimentaldesign as well as hands on sample preparation, mass spectrometry analysis, and primary data analysis. Multiple high performance mass spectrometers for LC-MS/MS experiments and MALDI TOF-TOF instruments are available for proteomic analyses. For protein identification from complex samples, analysis involves multidimensional LC-MS/MS followed by automated database searching with Sequest software running on a multiprocessor Linux cluster in the Advanced Computing Center for Research and Education (ACCRE). Protein identifications are evaluated, filtered, and compared using custom lDPicker or commercial Scaffold software. Additional data analysis by TagRecon enables identification of unanticipated modifications or sequence variants from MS/MS data. The Core also provides relative quantitation using stable isotope differential labeling strategies, iTRAQ and SILAC, for samples derived from animal models or from cell culture, respectively. Validation of protein expression changes is accomplished using multiple reaction monitoring LC-MS/MS methods. Project 1 (Peek) will utilize the iTRAQ method to measure proteomic changes in gastric epithelial cells from gerbils infected with carcinogenic H. pylori or mutants fed iron-replete and iron-deplete diets. Project 2 (Wilson) will utilize the same approach to determine changes in gastric epithelial cell proteomes upon EGFR activation. In addition, this Project will utilize the SILAC method to measure changes in the phosphoproteome upon EGFR activation in conditionally immortalized cells. Project 3 (Cover) will employ the iTRAQ method to measure differences in H. pylori output strains from gerbils fed high salt or regular diets. Targeted MRM validation will be employed in all studies to confirm specific proteomic changes

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA116087-06
Application #
8632358
Study Section
Special Emphasis Panel (ZCA1-RPRB-C (O1))
Project Start
2014-01-01
Project End
2018-12-31
Budget Start
2014-03-12
Budget End
2014-12-31
Support Year
6
Fiscal Year
2014
Total Cost
$173,978
Indirect Cost
$81,541
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Sierra, Johanna C; Asim, Mohammad; Verriere, Thomas G et al. (2017) Epidermal growth factor receptor inhibition downregulates Helicobacter pylori-induced epithelial inflammatory responses, DNA damage and gastric carcinogenesis. Gut :
Hardbower, Dana M; Asim, Mohammad; Luis, Paula B et al. (2017) Ornithine decarboxylase regulates M1 macrophage activation and mucosal inflammation via histone modifications. Proc Natl Acad Sci U S A 114:E751-E760
Gobert, Alain P; Wilson, Keith T (2017) Effect of CO2 on Peroxynitrite-Mediated Bacteria Killing: Response to Tsikas et al. Trends Microbiol 25:602-603
Kyburz, A; Urban, S; Altobelli, A et al. (2017) Helicobacter pylori and its secreted immunomodulator VacA protect against anaphylaxis in experimental models of food allergy. Clin Exp Allergy 47:1331-1341
Varga, Matthew Gordon; Peek, Richard M (2017) DNA Transfer and Toll-like Receptor Modulation by Helicobacter pylori. Curr Top Microbiol Immunol 400:169-193
Feichtinger, René G; Neureiter, Daniel; Skaria, Tom et al. (2017) Oxidative Phosphorylation System in Gastric Carcinomas and Gastritis. Oxid Med Cell Longev 2017:1320241
Loh, John T; Beckett, Amber C; Scholz, Matthew B et al. (2017) High salt conditions alter transcription of Helicobacter pylori genes encoding outer membrane proteins. Infect Immun :
Kim, Aeryun; Servetas, Stephanie L; Kang, Jieun et al. (2017) Correction: Helicobacter pylori bab Paralog Distribution and Association with cagA, vacA, and homA/B Genotypes in American and South Korean Clinical Isolates. PLoS One 12:e0176468
Xiong, Menghua; Bao, Yan; Xu, Xin et al. (2017) Selective killing of Helicobacter pylori with pH-responsive helix-coil conformation transitionable antimicrobial polypeptides. Proc Natl Acad Sci U S A 114:12675-12680
Zhu, Shoumin; Soutto, Mohammed; Chen, Zheng et al. (2017) Helicobacter pylori-induced cell death is counteracted by NF-?B-mediated transcription of DARPP-32. Gut 66:761-762

Showing the most recent 10 out of 189 publications