Richard M Peek
Vanderbilt University
Project start date: 2009-01-01
Project end date: 2013-12-31
Sponsored Links Excellgen http://Excellgen.com
Richard M Peek, Professor
Vanderbilt University, Medical Center, Nashville, Tn 37203-6869
Abstract: to all Program Project participants by Dr. Yu Shyr and Greg Ayers, the Administrative Core´s Biostatisticians. In addition, all Program-related meetings will be scheduled through this Core. These include monthly meetings of Project and Core leaders to evaluate productivity, allocate core usage and Program resources, and discuss future directions. A monthly scientific meeting will also allow investigators to present current data, identify problems, and discuss solutions. Arrangements for the Scientific Advisory Board meetings, planned for each year of the Project period, as well as generation of materials to be reviewed will be handled through the Administrative Core. The Administrative Core will organize and coordinate 1 retreat each year for Program Project participants and the Internal and External advisors. Finally, this Core will prepare, generate, and assemble materials required for the annual progress reports and will ensure that all additional NIH and institutional reporting requirements concerning the Program Project´s activities are completed in a timely manner. RELEVANCE (See instructions) This Core will facilitate activities required to identify factors that influence gastric carcinogenesis. PROJECT7PERFORMANCE SITE(S) (if additional space is needed, use Project/
Keywords: Administrative Coordination; Biostatistics Core; C. pylori; Campylobacter pylori; Cancer Induction; Cancer of the Fundus of the Stomach; Cancer of the Gastric Body; Cancer of the Gastric Cardia; Cancer of the Gastric Fundus; Cancer of the Gastric Pylorus; Cancer of the Pylorus of the Stomach; Communication; Core Facility; Data; Drug Formulations; E-Mail; Electronic Mail; Email; Ensure; Fees; Formulation; Formulations, Drug; Funding; Future; Gastric Cancer; Generations; Grant; H. pylori; H. pylory; H.pylori; Helicobacter pylori; Histopathology; Human Resources; INFLM; Individual; Inflammation; Instruction; Investigators; Malignant Gastric Neoplasm; Malignant Gastric Tumor; Malignant Tumor of the Stomach; Malignant neoplasm of stomach; Manpower; NIH; National Institutes of Health; National Institutes of Health (U.S.); Newsletter; P01 Mechanism; P01 Program; Participant; Preparation; Procedures; Productivity; Program Project Grant; Program Research Project Grants; Programs (PT); Programs [Publication Type]; Progress Reports; Proteomics; Reagent; Reporting; Reports, Progress; Research; Research Personnel; Research Program Projects; Research Resources; Researchers; Resource Development; Resources; SCHED; Schedule; Site; Solutions; Stomach; Stomach Cancer; Time; United States National Institutes of Health; Update; base; carcinogenesis; falls; gastric; malignant stomach neoplasm; meetings; member; new technology; personnel; programs; protocol development
Budget start date: 1-JAN-2010
Budget end date: 31-DEC-2010
5P01CA116087-02_8258 (2010): $149319
MECHANISMS THAT REGULATE HELICOBACTER PYLORI-INDUCED BETA-CATENIN ACTIVATION
Richard M Peek, Professor
Vanderbilt University, Medical Center, Nashville, Tn 37203-6869
Abstract: is needed, use Project/
Keywords: 3-10C; AMCF-I; Actins; Adenoma of the Stomach; Adenomatous Polyp of the Stomach; Adherence; Adherence (attribute); Attenuated; Binding; Binding (Molecular Function); Biological; C. pylori; CTNNB1; CUL-2; CXCL8; Cadherin-Associated Protein, Beta; Cadherin-Associated Protein, Beta 1 (88kD); Cadherins; Campylobacter pylori; Cancer Cause; Cancer Etiology; Cancer Induction; Cancer of the Fundus of the Stomach; Cancer of the Gastric Body; Cancer of the Gastric Cardia; Cancer of the Gastric Fundus; Cancer of the Gastric Pylorus; Cancer of the Pylorus of the Stomach; Cancers; Catenin, Beta-1; Cell Communication and Signaling; Cell Signaling; Cell-Cell Adhesion; Cellular Matrix; Cessation of life; Cytoskeletal System; Cytoskeleton; Data; Death; Development; Dysplasia; EGF; EGF gene; EGFR; ERBB Protein; ERBB1; Enhancers; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Kinase; Epidermal Growth Factor Receptor Protein-Tyrosine Kinase; Epithelial; Epithelial Cells; Epithelium; Event; GCP-1; GCP1; GFAC; Gastric Adenocarcinoma; Gastric Adenoma; Gastric Adenomatous Polyp; Gastric Cancer; Gastric Inflammation; Gastritis; Genes; Gerbils; Growth Agents; Growth Factor; Growth Factors, Proteins; Growth Substances; H. pylori; H. pylory; H.pylori; HER1; Harvest; Helicobacter pylori; Histologic; Histologically; Human; Human, General; IL-8; IL8; IL8 gene; INFLM; In Vitro; Inflammation; Inflammatory; Injury; Intracellular Communication and Signaling; K60; LECT; LEF Transcription Factor; LUCT; LYNAP; Link; Liver Cell Adhesion Molecules; Lymphocyte; Lymphocytic; Lymphoid Enhancer Factor; MDNCF; MMPs; MONAP; Malignant Gastric Neoplasm; Malignant Gastric Tumor; Malignant Neoplasms; Malignant Tumor; Malignant Tumor of the Stomach; Malignant neoplasm of stomach; Mammals, Mice; Mammals, Rodents; Man (Taxonomy); Man, Modern; Matrix Metalloproteinases; Mediating; Membrane; Mice; Microbe; Modeling; Molecular; Molecular Interaction; Mucosal Inflammation; Mucositis; Murine; Mus; NAF; Nuclear; Nuclear Translocation; PRO2286; Pathogenicity; Pathway interactions; Persons; Phenotype; Phosphorylation; Protein Phosphorylation; Publications; Pylorus; Receptor Protein; Receptor, EGF; Receptor, TGF-alpha; Receptor, Urogastrone; Receptors, Epidermal Growth Factor-Urogastrone; Reporter; Risk; Risk Factors; Rodent; Rodent Model; Rodentia; Rodentias; SCYB8; Scientific Publication; Signal Pathway; Signal Transduction; Signal Transduction Systems; Signaling; Staging; Stomach; Stomach Adenocarcinoma; Stomach Cancer; T Cell Factor; TCF Transcription Factor; TSG-1; Time; Transcription Activation; Transcriptional Activation; Transforming Growth Factor alpha Receptor; Transgenic Organisms; URG; Up-Regulation; b-ENAP; beta catenin; biological signal transduction; c-erbB-1; c-erbB-1 Protein; carcinogenesis; cytokine; dyscrasia; erbB-1; erbB-1 Proto-Oncogene Protein; erbBl; gastric; in vivo; intracellular skeleton; liver cell adhesion molecule; lymph cell; malignancy; malignant stomach neoplasm; membrane structure; mutant; neoplasm/cancer; pathogen; pathway; proto-oncogene protein c-erbB-1; receptor; response; transgenic
Budget start date: 1-JAN-2010
Budget end date: 31-DEC-2010
5P01CA116087-02_8253 (2010): $281794
H. PYLORI-INDUCED INFLAMMATION AND GASTRIC CANCER
Richard M Peek, Professor
Vanderbilt University, Medical Center, Nashville, Tn 37203-6869
Grant 5P01CA116087-02 from National Cancer Institute
Abstract: Gastric adenocarcinoma is the second leading cause of cancer-related death in the world, and Helicobacter pylori is the strongest identified risk factor for this malignancy, yet only a fraction of colonized persons ever develop neoplasia. One H. pylori determinant associated with gastric cancer is the cag pathogenicity island, and several cag genes encode components of a type IV secretion system which exports bacterial proteins such as CagA into host epithelial cells. Our group has now demonstrated that H. pylori cag+ strains selectively activate ?-catenin and the EGF receptor (EGFR), host effectors that influence carcinogenesis, in gastric epithelial cells. We have also demonstrated that an environmental factor associated with gastric cancer, salt, augments the ability of H. pylori cag+ strains to induce aberrant epithelial responses. Therefore, the overarching objective of this Application is delineation of the molecular signaling events initiated by H. pyloriepithelial cell contact that regulate phenotypes related to gastric carcinogenesis. This PPG will integrate studies of host-pathogen interactions initiated by biomedical researchers who have made a strong and clear commitment to research within the fields of gastroenterology, cancer biology, carcinogenesis, and microbiology, and will generate results that would not be attainable through independent investigation. The component Projects are driven by discrete hypotheses, yet are cohesive in that each focuses on H. pyloriepithelial interactions that induce cellular responses with carcinogenic potential. The individual projects include Project 1. Mechanisms that regulate Helicobacter pylori-induced ?-catenin activation (PI-Richard Peek). Project 2. EGFR activation in H. pylori-induced gastric cancer (PI-Brent Polk). Project 3. Helicobacter pylori cag pathogenicity island and gastric carcinogenesis (PI-Timothy Cover). The efforts of each Project will be further unified by dynamic interactions with Specific Core facilities, which include the Gastric Histopathology Core (Core A), the Proteomics Core (Core B), and an Administrative Core (Core C). By maintaining a grounded focus on fundamental interactions that occur at the H. pyloriepithelial interface, results from this proposal will not only improve our understanding of gastric cancer, but will also facilitate identification of potential therapeutic targets for prevention and more effective treatment of this disease
Project start date: 2009-01-01
Project end date: 2013-12-31
Budget start date: 1-JAN-2010
Budget end date: 31-DEC-2010
5P01CA116087-02 (2010): $1450893
Grants awarded to Richard M Peek
Richard M Peek, Professor
Vanderbilt University Medical Center Nashville, Tn 372036869
Grant 5T32DK007673-15 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: ZDK1
Abstract: This application requests continued support for a combined adult-pediatric GI research training program. The objective of the program is to prepare pre-and postdoctoral fellows for investigative careers in digestive diseases by training them in basic research utilizing molecular, genetic and cellular methods or in clinical research through formal studies in clinical science/epidemiology. The training faculty represents 4 major areas of interest 1) growth regulation proliferation and apoptosis, 2) maintenance of epithelial integrity, 3) enteric neuroscience, and 4) clinical epidemiology and outcomes research. Each group is led by an NIH funded senior faculty member. There is extensive collaboration between trainers and all of them have training experience and independent research funding. Basic laboratory research training will be carried out under the direction of a preceptor selected from the trainers included in our application. An advisory committee will oversee the training and assist the preceptor in selecting a project and in experimental design. Didactic courses in basic science departments will be required by the advisory committee for trainees who do not have formal training in basic science. The clinical epidemiology trainees will be supervised by a clinician-scientist preceptor. An advisory committee will oversee their training and assist in designing their research project. Physician trainees wilt be free from all clinical duties except the continuity clinic during their research and course work. Five regular postdoctoral positions are requested. Two positions will be available for pediatric digestive disease trainees, two for adult digestive disease trainees, and one is unspecified. Two predoctoral positions are requested to expand our digestive disease program. In addition, two summer minority positions are requested. This training proposal has been instrumental in the development of digestive disease research at Vanderbilt. During our past funding period we have supported 16 individuals from our GI Training proposal (detailed in our Summary of Research Trainees section). 8 of these individuals are presently still engaged in training. 7 of the 8 individuals who have finished training have taken academic positions and 1 has taken a research position in Industry. Of our 16 trainees from the past period, 4 were women and 1 was a minority (American Indian). We are encouraged by our ability to successfully train academic investigators. 6 of the 8 individuals currently in training are currently planning careers in academic medicine
Project start date: 1992-07-01
Project end date: 2008-06-30
5T32DK007673-15 (2007): $216360
5T32DK007673-14 (2006): $382247
5T32DK007673-13 (2005): $294407
5T32DK007673-12 (2004): $297772
TRAINING GRANT IN GASTROENTEROLOGY
Richard M Peek, Professor
Vanderbilt University, Medical Center, Nashville, Tn 37203-6869
Grant 3T32DK007673-18S1 from National Institute Of Diabetes And Digestive And Kidney Diseases
Abstract: There is a tremendous need to increase the number of academic investigators who perform research that will directly impact the care of patients with digestive diseases. This proposal describes the continuation of the combined adult-pediatric Training in Gastroenterology Program that provides multidisciplinary training for postdoctoral scientists in basic research or in clinical/translational research through formal studies in clinical science or epidemiology. This highly focused training program involves 32 funded preceptors (aggregate funding >$30 million direct costs/year) in 10 different academic departments or research centers at Vanderbilt University who have an extensive history of collaboration. All preceptors (31 tenured full or associate professors) have strong records of accomplishment in basic or clinical research related to digestive diseases and a deep commitment to training postdoctoral fellows. In addition to this composite group of training faculty, we have identified 3 junior investigators previously supported by this grant who are expected to develop into preceptors during the next funding period. Dr. Richard Peek, M.D. will continue to serve as Program Director and is well qualified to provide leadership to this program. Dr. Peek is Director of the Division of Adult Gastroenterology and has 14 years of experience studying gastric carcinogenesis. He will be assisted by the co-PI of this grant, Dr. Brent Polk, Director of the Division of Pediatric Gastroenterology and the Digestive Diseases Research Center at Vanderbilt, as well as an Oversight and Selection Committee composed of senior faculty deeply invested in training fellows in this area. Postdoctoral trainees will be selected primarily from the pool of fellows accepted into the Adult and Pediatric Gl training programs as well as applicants that apply to individual preceptor laboratories. A multi-faceted recruitment strategy will continue to attract highly qualified individuals from underrepresented minority groups. Basic laboratory research training will be carried out under the direction of a preceptor selected from the trainers included in this application. Clinical epidemiology trainees will be supervised by a clinician-scientist preceptor. An advisory committee will oversee training and provide assistance in research project design for all trainees. In addition to intensive research experiences, trainees will have rigorous didactic course requirements as well as formal mentoring and career guidance. Seven postdoctoral positions and two summer minority positions per year are requested. Lay summary The goal of this training program is to develop scientists with strong commitments to academic biomedical research in the area of digestive diseases
Keywords: Gastroenterology; Grant; Training
Project start date: 1992-07-01
Project end date: 2013-06-30
Budget start date: 1-JUL-2010
Budget end date: 30-JUN-2011
PFA/PA: PA-06-468
3T32DK007673-18S1 (2010): $63695
5T32DK007673-18 (2010): $318752
5T32DK007673-17 (2009): $311050
3T32DK007673-17S1 (2009): $65315
2T32DK007673-16 (2008): $277033
3T32DK007673-16S1 (2008): $62710
Sponsored Links Excellgen http://Excellgen.com
H PYLORI RELATIONSHIP TO DIGESTIVE DISEASES AND CANCER
Richard M Peek, Professor
Medicinevanderbilt University
medical Center
nashville, Tn 372036869
Grant 5R29CA077955-05 from National Cancer Institute IRG: ZDK1
Abstract: taken ) Persistent H. pylori infection is an important etiologic factor for the development of atrophic gastritis and gastric adenocarcinoma; however, only a small percentage of infected persons develop neoplasia. Enhanced cancer risk may be related to differences in expression of specific bacterial products, differences in host response to the bacteria, or both. H. pylori strains that possess cagA are associated with increased severity of gastritis and with additional risk for developing atrophic gastritis and cancer. One mechanism contributing to neoplastic transformation may be inhibition of epithelial cell apoptosis, a process regulated by transcription factors such as NF-KappaB and p53. Our hypothesis is that the increased malignant potential of H. pylori cagA+ strains is dependent on the ability to selectively affect eukaryotic proteins that regulate multiple cellular pathways which results in both heightened inflammation and decreased apoptosis. Since the effect of H. pylori on programmed cell death is likely to be complex, this project is being submitted as one component of an interactive proposal with Dr. Duane Smoot of Howard University. Dr. Smoot´s in vitro studies will primarily focus on downstream effectors of NF-KappaB-dependent apoptosis such as nitric oxide, reactive oxygen intermediates, and Bc1-2 related proteins which will complement our experiments on H. pylori and NF-KappaB in gastric epithelial cells and gastric mucosa. This collaborative approach should facilitate elucidation of specific mechanisms by which H. pylori alters apoptosis and predisposes infected individuals to carcinogenesis. The long-term objective of this proposal is to examine the molecular mechanisms by which H. pylori strains selectively affect apoptosis in vitro and in vivo. First, we plan to determine whether wild-type H. pylori strains of varying genotype differentially affect NF-KappaB dependent apoptosis, using an in vitro model of gastric epithelial cell interaction with H. pylori. Using isogenic mutant strains containing inactivation cassettes within cagA, picA, picB, vacA, and iceA, we also will determine the role of specific H. pylori virulence determinants in eukaryotic apoptosis. Second, we will determine the effect of wild-type and isogenic H. pylori mutant strains on gastric epithelial cell apoptosis and NF-KappaB-dependent apoptosis in vivo using a rodent model of infection. Third, we will examine the effect of H. pylori on mediators of gastric epithelial cell apoptosis in vivo in p53-deficient mice. From these studies, as well as from Dr. Smoot´s experiments, we can begin to dissect the pathways that are activated in gastric epithelial cells following interaction with H. pylori that may play a role in the subsequent development of gastric cancer
Keywords: Helicobacter, adenocarcinoma, bacterial disease, gastritis, stomach neoplasm apoptosis, carcinogenesis, disease /disorder etiology, free radical oxygen, gastric mucosa, gastrointestinal epithelium, host organism interaction, neoplasm /cancer genetics, nitric oxide, transcription factor, tumor suppressor protein animal genetic material tag, clinical research, gerbil /jird, human genetic material tag, human subject, laboratory mouse
Project start date: 1997-09-30
Project end date: 2002-09-29
5R29CA077955-05 (2001): $152000
5R29CA077955-04 (2000): $142163
5R29CA077955-03 (1999): $70257
1R29CA077955-01 (1997): $88129
Helicobacter Pylori And Gastrointestinal Biology
Richard M Peek, Professor
Vanderbilt University Medical Center Nashville, Tn 372036869
Grant 5R01DK058587-05 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: GMA
Abstract: Persistent H. pylori infection is a risk factor for atrophic gastritis and distal gastric adenocarcinoma; however, only a small percentage of colonized persons develop neoplasia. Enhanced cancer risk may be related to differences in expression of specific bacterial products, to differences in host response to the bacteria, or to the specific interactions between host and microbe. H. pylori strains that possess the cag pathogenicity island induce more severe gastritis and are associated with an additional risk for developing atrophy and gastric cancer. A specific mechanism by which cagA+ strains may lower the threshold for carcinogenesis is by altering epithelial cell proliferation and apoptosis, processes that can be regulated by host inflammatory mediators such as prostaglandin products of cyclooxygenase-2 (COX-2). Over-expression of COX-2 in vitro inhibits apoptosis, and COX-2 is up-regulated within H. pylori-induced gastritis, atrophic gastritis, and gastric adenocarcinoma specimens. In vitro, H. pylori cagA+ strains stimulate COX-2 expression in gastric epithelial cells. Since we and others have shown that cagA+ strains are associated with increased gastric epithelial cell proliferation but attenuated apoptosis in vivo, induction of COX-2 by strain-specific microbial factors may represent a specific mechanism by which certain H. pylori strains heighten the risk for gastric adenocarcinoma. The long-term objective of this proposal is to examine the molecular mechanisms by which H. pylori strains selectively affect COX-2 regulated epithelial cellular turnover in vitro and in vivo. To address this, we will first determine whether H. pylori or secreted bacterial products alter COX-2-dependent apoptosis in a novel in vitro model of bacterialgastric epithelial cell interaction (conditionally immortalized gastric epithelial cells). COX-2 expression will also be examined in myofibroblasts co-cultured with H. pylori and epithelial cells to more closely approximate events occurring within native gastric mucosa. Second, we will determine whether H. pylori infection affects COX-2-dependent cellular turnover in wild-type and COX-2 deficient mice. Third, we will investigate the role of specific H. pylori determinants on COX-2-regulated cellular responses by inactivating strain-specific genes identified by H. pylori whole genome microarray. H. pylori parental and isogenic mutant strains will then be co-incubated with conditionally immortalized cells and infected into mice. The effects of strain-specific bacterial factors and COX-2 generated products also will be investigated in a murine model of gastric carcinogenesis, INS-GAS hypergastrinemic mice. Systematic studies of each of these variables in vitro and in animal systems that reflect H. pylori pathogenesis in humans should help elucidate their relative importance, direct the course of future intervention and prevention strategies, and potentially provide a model of carcinogenesis arising within the context of chronic mucosal inflammation.
Keywords: Helicobacter, bacterial genetics, carcinogenesis, gastrointestinal epithelium, gastrointestinal infection, genetic strain, host organism interaction, apoptosis, cell transformation, nucleic acid sequence, prostaglandin endoperoxide synthase, virulence, laboratory mouse, microarray technology, mixed tissue /cell culture, tissue /cell culture
Project start date: 2001-08-01
Project end date: 2008-08-31
5R01DK058587-05 (2005): $286900
5R01DK058587-04 (2004): $286900
5R01DK058587-03 (2003): $286900
5R01DK058587-02 (2002): $286900
1R01DK058587-01A1 (2001): $273543
H. PYLORI RELATIONSHIP TO DIGESTIVE DISEASES AND CANCER
Richard M Peek, Professor
Vanderbilt University, Medical Center, Nashville, Tn 37203-6869
Grant 5R01CA077955-13 from National Cancer Institute
Abstract: Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, yet only a fraction of infected persons ever develop cancer. One H. pylori determinant that augments cancer risk is the cag pathogenicity island, which translocates bacterial proteins into host cells following adherence. Since contact between H. pylori and gastric epithelial cells is critical for induction of injury, the long-term objective of R01 grant CA 77955 is to define mechanisms through which H. pylori induce epithelial responses with carcinogenic potential. A host molecule that may influence carcinogenesis in conjunction with H. pylori is matrix metalloproteinase-7 (MMP-7). MMP-7 attenuates apoptosis and we have demonstrated that MMP-7 is expressed exclusively in human mucosa colonized by H. pylori cag+ strains and that these strains selectively induce MMP-7 through cag-mediated activation of ERK1/2. Our studies now show that up-regulation of MMP-7 by H. pylori also requires p120-catenin (p120). p120 functions as a transcription factor by forming complexes with Kaiso, a transcriptional repressor implicated in tumorigenesis. Over-expression of p120 relieves Kaiso-mediated transcriptional repression of MMP-7, and our data show that H. pylori-induced up-regulation of MMP-7 is mediated by p120 and Kaiso in vitro and in an ex vivo gastric gland culture model system. Rodent models provide valuable insights into gastric carcinogenesis, and our studies now demonstrate that a rodent-adapted derivative (7.13) of a human H. pylori cag+ strain induces gastric cancer in Mongolian gerbils by 4 weeks and in hypergastrinemic (INS-GAS) mice by 24 weeks. Using this strain as a prototype, we show that strain 7.13 selectively activates epidermal growth factor receptor (EGFR) and ERK1/2, a downstream mediator of EGFR, in vitro. Activation of EGFR attenuates apoptosis in response to strain 7.13 and is required for up-regulation of MMP-7. Since EGFR transactivation can directly phosphorylate p120, our hypothesis is that selective activation of p120-dependent pathways by H. pylori cag+ strains contributes to the augmentation in carcinogenic risk conferred by these strains by attenuating epithelial apoptosis. Our specific aims are 1. To define the effects of wild-type and isogenic mutant H. pylori strains on p120-dependent cellular responses related to carcinogenesis in vitro. 2. To define the host signaling pathways that regulate H. pylori-induced p120 activation. 3. To define the effects of p120 and EGFR on H. pylori-induced injury in vivo. These studies will define bacterial and host factors that influence gastric cancer. Such findings may help to identify H. pylori-infected persons at high risk for gastric cancer, who thereby warrant therapy
Keywords: Actins; Address; Adherence; Adherence (attribute); Animal Model; Animal Models and Related Studies; Animals; Apoptosis; Apoptosis Pathway; Apoptotic; Attenuated; Bacterial Gene Proteins; Bacterial Proteins; Biological; Biological Models; C. pylori; Campylobacter pylori; Cancer Cause; Cancer Etiology; Cancer Induction; Cancer of the Fundus of the Stomach; Cancer of the Gastric Body; Cancer of the Gastric Cardia; Cancer of the Gastric Fundus; Cancer of the Gastric Pylorus; Cancer of the Pylorus of the Stomach; Cancers; Cell Communication and Signaling; Cell Culture Techniques; Cell Death, Programmed; Cell Nucleus; Cell Signaling; Cell-Cell Adhesion; Cells; Cessation of life; Complex; Data; Death; Development; Digestive Diseases; Digestive System Diseases; Digestive System Disorders; EGFR; ERBB Protein; ERBB1; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Kinase; Epidermal Growth Factor Receptor Protein-Tyrosine Kinase; Epithelial; Epithelial Cells; Fundic Gland; Funding; Gastric Adenocarcinoma; Gastric Cancer; Gastric Glands; Gastric mucosa; Gene Down-Regulation; Gene Products, Bacterial; Gerbils; Glands, Gastric; Grant; H. pylori; H. pylory; H.pylori; HER1; Helicobacter Infections; Helicobacter Pylori Infection; Helicobacter pylori; Host Factor; Host Factor Protein; Human; Human, General; In Vitro; Inflammatory; Injury; Integration Host Factors; Intracellular Communication and Signaling; Island; Lesion; Link; MMP-7; MMPs; Malignant; Malignant - descriptor; Malignant Gastric Neoplasm; Malignant Gastric Tumor; Malignant Neoplasms; Malignant Tumor; Malignant Tumor of the Stomach; Malignant neoplasm of stomach; Mammals, Mice; Mammals, Rodents; Man (Taxonomy); Man, Modern; Matrilysin; Matrin; Matrix Metalloproteinase-7; Matrix Metalloproteinases; Mediating; Mediator; Mediator of Activation; Mediator of activation protein; Membrane; Mice; Model System; Modeling; Models, Biologic; Mucosa; Mucosal Tissue; Mucous Membrane; Murine; Mus; Nuclear Translocation; Nucleus; Oncogenesis; PUMP-1; Pathogenicity Island; Pathway interactions; Persons; Pre-Malignant; Premalignant; Proteins; Publications; Pylorus; Receptor, EGF; Receptor, TGF-alpha; Receptor, Urogastrone; Receptors, Epidermal Growth Factor-Urogastrone; Risk; Risk Factors; Rodent; Rodent Model; Rodentia; Rodentias; Scientific Publication; Signal Pathway; Signal Transduction; Signal Transduction Systems; Signaling; Stomach; Stomach Adenocarcinoma; Stomach Cancer; System; System, LOINC Axis 4; Time; Trans-Activation (Genetics); Transactivation; Transcription Corepressor; Transcription Repression; Transcription Repressor; Transcription Repressor/Corepressor; Transcriptional Corepressor; Transcriptional Repression; Transcriptional Repressor; Transcriptional Repressor/Corepressor; Transforming Growth Factor alpha Receptor; Up-Regulation; Up-Regulation (Physiology); Upregulation; biological signal transduction; c-erbB-1; c-erbB-1 Protein; cancer risk; carcinogenesis; cytokine; digestive disorder; erbB-1; erbB-1 Proto-Oncogene Protein; erbBl; gastric; gene product; gene repression; high risk; in vivo; insight; malignancy; malignant stomach neoplasm; membrane structure; microbial; model organism; mutant; neoplasm/cancer; pathogen; pathway; precancerous; proto-oncogene protein c-erbB-1; prototype; public health relevance; response; transcription factor; tumor; tumorigenesis
Project start date: 1997-09-30
Project end date: 2013-03-31
Budget start date: 1-APR-2010
Budget end date: 31-MAR-2011
PFA/PA: PA-07-070
5R01CA077955-13 (2010): $351737
Sponsored Links Excellgen http://Excellgen.com
PATHOGENESIS OF H PYLORI INDUCED GASTRIC INFLAMMATION
Richard M Peek, Professor
Vanderbilt University Medical Center Nashville, Tn 372036869
Grant 5K08DK002381-05 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: SRC
Abstract: Helicobacter pylori infection results in chronic superficial gastritis and plays an important role in the pathogenesis of duodenal and gastric ulcer disease. The chronic inflammatory process associated with the infection has also been linked to atrophic gastritis, gastric adenocarcinoma and non-Hodgkins lymphoma of the stomach. Infection is clinically silent in many, if not most, persons but its high prevalence worldwide results in substantial morbidity and mortality from peptic ulcer disease and gastric cancer. The factors that lead infected persons to develop clinical disease or remain asymptomatic are poorly understood. H. pylori strain-specific differences or variations in the host response to the infection alone, or in combination, may determine a particular pathologic outcome. The long term goals of this project are to gain an understanding of the inflammatory and immunologic events which develop in response to H. pylori infection, to identify host responses and strain-specific products that lead to distinct pathological outcomes, and to define the mechanisms by which specific bacterial products lead to divergent outcomes. To achieve these goals, the specific aims proposed are 1) to determine whether in vivo expression of the products of H. pylori strain-specific genes such as cagA and particular alleles of vacA, encoding the vacuolating cytotoxin induces characteristic patterns of cytokine production that are associated with peptic ulcer disease; 2) to identify and clone novel H. pylori genes that are induced by adherence to gastric epithelium, correlate gene expression with pathologic outcome, and examine the function of these genes; 3) to examine the effect of isogenic mutations within H. pylori virulence genes on cytokine production in vitro.
Keywords: Helicobacter, duodenal ulcer, gastritis, molecular pathology, pathologic process, allele, bacterial genetics, cytokine, cytotoxicity, gastrointestinal epithelium, gene expression, gene induction /repression, gene mutation, genetic strain, host organism interaction, interferon, interleukin 8, virulence, biopsy, endoscopy, enzyme linked immunosorbent assay, molecular cloning, polymerase chain reaction
Project start date: 1996-07-01
Project end date: 2001-06-30
5K08DK002381-05 (2000): $98202
5K08DK002381-04 (1999): $95971
5K08DK002381-03 (1998): $93804
5K08DK002381-02 (1997): $87426
H.Pylori Relationship To Digestive Diseases And Cancer
Richard M Peek, Professor
Vanderbilt University Medical Center Nashville, Tn 372036869
Grant 5R01CA077955-10 from National Cancer Institute IRG: GMA
Abstract: H. pylori colonization increases the risk for gastric adenocarcinoma yet only a fraction of infected persons ever develop cancer. H. pylori strains that contain the cag pathogenicity island (cag+) augment the risk for severe gastritis and gastric cancer, and we have shown that cag genes are required for the development of inflammation in a rodent model of H. pylori-induced gastric cancer. Our data also demonstrate that cag genes are necessary for induction of proinflammatory cytokine release and apoptosis in gastric epithelial cells in vitro, events mediated by NF-(B and/or mitogen-activated protein kinases (MAPK). In vivo, however, heterogeneity exists among apoptosis scores within infected populations, and one explanation for such variability is H. pylori genetic diversity. Gastric epithelial cell proliferation is higher but apoptotic indices are lower among persons colonized with cag+ compared to cag- strains or uninfected persons, and reduced rates of cell loss, when accompanied by hyperproliferation, may heighten retention of mutagenized cells, which could predispose towards malignancy. One host effector that may influence carcinogenic pathways associated with H. pylori is matrilysin, a matrix metalloproteinase that enhances tumor formation, and is over-expressed in premalignant and malignant lesions within H. pylon-infected human mucosa. Constitutive expression of matrilysin selects for cells with a reduced sensitivity to apoptosis, and we now show that matrilysin is detected exclusively in human mucosa colonized by cag+ strains, and these strains selectively induce matrilysin in vitro through cag-mediated activation of NF-(B and MAPK. Another host pathway through which inflammatory mediators may influence pathogenesis is PPAR(, a nuclear transcription factor. Our data now show that PPAR( activation inhibits H. pylori-induced NF-(B signaling in vitro, and attenuates inflammation and injury in rodent models of H. pylori-induced gastritis. Our hypothesis is that strain-selective activation of NF-(B and/or MAPK by cag+ strains regulates matrilysin expression which may contribute to the augmentation in carcinogenic risk associated with these strains by attenuatinq apoptosis within colonized mucosa, and that PPAR( activation suppresses phenotypes related to carcinogenesis by inhibiting H. pylori-induced NF-(B-mediated responses in gastric epithelial cells. To address this, our specific aims are 1) To determine the effects of H. pylori and mutant strains on matrilysin-dependent cellular responses related to carcinogenesis in vitro and in matrilysin deficient mice; 2) To identify targets of PPAR( that suppress H. pylori-induced epithelial responses associated with oncogenesis; and 3) To determine the role of PPAR( in regulating inflammatory and injury responses to H. pylori using in vivo models of PPAR( pharmacologic activation and genetic deficiency. Studies of these variables in vitro and in animal systems that reflect pathogenesis in humans will not only improve our understanding of H. pylori-induced carcinogenesis and facilitate identification of potential therapeutic targets, but may also provide insights into other malignancies that arise within the context of inflammatory states.
Keywords: Helicobacter, bacterial genetics, cancer risk, carcinogenesis, host organism interaction, stomach neoplasm, virulence, apoptosis, bacterial disease, cytokine, disease /disorder etiology, gastritis, gastrointestinal epithelium, inflammation, metalloendopeptidase, mitogen activated protein kinase, neoplasm /cancer genetics, nitric oxide, peroxisome proliferator activated receptor, biopsy, clinical research, human subject, laboratory mouse, mutant
Project start date: 1997-09-30
Project end date: 2008-03-31
5R01CA077955-10 (2007): $336463
5R01CA077955-09 (2006): $346511
5R01CA077955-08 (2005): $354850
5R01CA077955-07 (2004): $351126
2R01CA077955-06 (2003): $369618
Mechanism That Regulate Helicobacter Pylori-induced Beta-caterin Activation
Richard M Peek, Professor
Vanderbilt University Medical Center Nashville, Tn 372036869
Grant 5R01DK073902-02 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: ZRG1
Abstract: Gastric adenocarcinoma is the second leading cause of cancer-related death in the world. H. pylori is the strongest known risk factor for this malignancy, yet only a fraction of infected persons ever develop cancer. One H. pylori determinant that augments cancer risk is the cag pathogenicity island, and several cag genes encode components of a type IV bacterial secretion system which functions to export proteins (e.g., CagA) into host epithelial cells. A host effector that may influence carcinogenesis is ?-catenin, a downstream component of the Wnt pathway. When Wnt signaling is inactive, ??catenin is constitutively phosphorylated and degraded; binding of Wnt to its receptor inhibits ?-catenin phosphorylation, leading to its nuclear accumulation and the transcriptional activation of genes that influence carcinogenesis. Nuclear accumulation of ?-catenin is increased in gastric adenoma and dysplasia specimens, histologic stages that precede gastric adenocarcinoma. Our preliminary studies now demonstrate that a rodent-adapted H. pylori cag+ strain (7.13) rapidly induces gastric cancer in hypergastrinemic (INS-GAS) mice by 24 weeks and in Mongolian gerbils by 4 weeks. H. pylori strain 7.13 also induces nuclear translocation of ?-catenin and activates a ?-catenin-responsive reporter in vitro, indicating that ?-catenin is functionally responsive to this prototype strain. ?-catenin activation by H. pylori is dependent upon translocation of CagA into epithelial cells, and nuclear accumulation of ?-catenin is increased in gastric epithelium harvested from cag+-infected persons, compared to subjects carrying cag- strains or uninfected persons. Our hypothesis is that H. pylori cag+ strains selectively activate host signaling pathways, such as those mediated by ?-catenin, thereby regulating cellular responses that contribute to the augmentation in carcinogenic risk associated with these strains. Thus, our specific aims are 1. To define the effects of H. pylori constituents on activation of ?-catenin in vitro and in vivo. 2. To define the host signaling pathways that regulate H. pylori-induced ?-catenin activation. 3. To define differences in epithelial molecular responses to carcinogenic H. pylori versus mutant strains using a transgenic murine model of gastric cancer.
Keywords: Helicobacter, cell, actin, adenocarcinoma, adenoma, cadherin, cancer risk, carcinogenesis, cell adhesion, cytokine, cytoskeleton, death, epithelium, gene, gene expression, gene induction /repression, gerbil /jird, growth factor, growth factor receptor, human, inflammation, injury, lead, lymphocyte, membrane, model, mutant, neoplasm /cancer, phenotype, phosphorylation, protein, receptor, secretion, stomach neoplasm, transcription factor, clinical research
Project start date: 2006-04-01
Project end date: 2010-12-31
5R01DK073902-02 (2007): $296024
Sponsored Links Excellgen http://Excellgen.com
1R01DK073902-01 (2006): $303110
Inhibition Of Pathogen-induced NFkBmediated Inflammation
Richard M Peek, Professor
Vanderbilt University Medical Center Nashville, Tn 372036869
Grant 5R21AI058064-02 from National Institute Of Allergy And Infectious Diseases IRG: GMA
Abstract: Food and water represent the easiest vehicles to disperse biological agents in this country and individuals have already utilized the food supply as a means for terrorism. Many foodborne pathogens classified as high-priority by the Biodefense and Emerging Infectious Diseases Research Opportunities utilize a common pathway, NF-?B, to exacerbate the host inflammatory response, which dictates disease manifestations. For example, S. typhimurium induces NF-?B-mediated IL-8 secretion from intestinal epithelial cells leading to mucosal inflammation and the clinical manifestations of dysentery, which can be life-threatening. The high frequency and ease of dissemination of foodbome pathggens underscores the need to identify novel pharmacolog!c approaches that may eliminate diseases caused by these agents. Since the production of proinflammatory mediators in response to many of these organisms is regulated by NF-?B, inhibition of microbially-induced NF-?B has the potential to attenuate the host inflammatory response, which if left untreated, may progress to severe complications of enterocolitis and/or systemic illness. One specific constituent that may influence host inflammatory responses to bacteria is the ligand-activated transcription factor PPAR(. PPAR( activation attenuates IL-8 secretion by colonic epithelial cells in vitro and reduces inflammation in murine models of colitis via inhibition of NF-?B. We have similarly shown that PPAR(, activation inhibition NF-?B-mediated IL-8 secretion induced by the gastric pathogen Helicobacter pylori, and attenuates inflammation in two rodent models of H. pylon induced gastritis, underscoring the anti-inflammatory activity of this receptor. These results provide tantalizing evidence that PPAR( activators may represent novel therapies for inflammatory disorders that develop within the gastrointestinal tract. Our hypothesis is that inhibition of NF-?B signaling by PPAR( has the potential to Suppress inflammatory responses and disease induced by foodborne pathogens, Therefore, our Specific Aims are 1) To determine mechanisms through which microbialiy-induced NF-?B activation is suppressed by PPAR(, in model intestinal epithelia, using S. typhimurium as a prototype organism. 2)To identify and functionally characterize PPAR( target genes and microbially-induced NF-?B-regulated genes that are suppressed by PPAR(, activation using an in vitro model of intestinal epithelial cell inflammation.
Keywords: food chain contamination, inflammation, nuclear factor kappa beta, peroxisome proliferator activated receptor, Salmonella food poisoning, gastrointestinal epithelium, Salmonella typhimurium, bioterrorism /chemical warfare, cell line, enzyme linked immunosorbent assay
Project start date: 2004-01-01
Project end date: 2005-12-31
5R21AI058064-02 (2005): $302000
1R21AI058064-01 (2004): $302000
MOLECULAR AND CELLULAR BASIS FOR DIGESTIVE DISEASES
Richard M Peek
Vanderbilt University, Medical Center, Nashville, Tn 37203-6869
Grant 5P30DK058404-09 from National Institute Of Diabetes And Digestive And Kidney Diseases
Abstract: DESCRIPTION, OVERALL This application is for continued support of the Vanderbilt Digestive Disease Research Center (VDDRC) focused on the study of the molecular and cellular mechanisms responsible for digestive diseases. We believe that a fundamental understanding of these processes will provide a rational basis for development of targeted prevention and therapies. The VDDRC is multidisciplinary, including faculty in 10 different academic departments with 77 investigators (50 full members and 27 associate members). The Aims of the VDDRC are aligned with the goals of Vanderbilt University 1) to promote digestive diseases-related research in an integrative, collaborative and multidisciplinary manner; 2) to enhance the basic research capabilities of VDDRC Members; 3) to attract investigators not involved in digestive diseases-related research to pursue these lines of investigation; 4) to develop and implement programs for training, establishment, and retention of young investigators in digestive disease-related research; and 5) to facilitate the transfer of basic research findings to improvements in prevention and/or clinical care. Investigative interests of the members fall into four broad areas of study 1) growth, proliferation, and apoptosis, 2) epithelial integrity, 3) gastrointestinal development and function, and 4) gastrointestinal physiology, obesity, and metabolism. The VDDRC contains five core research laboratories to support the members 1) the Microarray Core, 2) the Cellular and Animal Modeling Core, 3) the Cell Imaging Core, 4) the Bioanalytical (Mass Spectrometry) and Proteomics Core, and 5) the Flow Cytometry Core. These are integrated into our Center to provide investigators working on digestive disease-related research with the latest advances in technology and aid in experimental design and interpretation of results. The VDDRC supports a Pilot/Feasibility Program including a university-supported translational project, and a Young Investigator Award Program to foster participation of beginning and seasoned investigators in research related to digestive diseases. The Administrative Core also contains Biostatistical and Enrichment Programs and oversees the financial management and operation of the VDDRC. The VDDRC Research Programs through technologies provided by the Research Cores are designed to improve prevention, management, outcomes or treatment of human digestive diseases
Project start date: 2000-12-01
Project end date: 2012-05-31
Budget start date: 1-JUN-2010
Budget end date: 31-MAY-2011
PFA/PA: RFA-DK-06-007
5P30DK058404-09 (2010): $1151250
HELICOBACTER PYLORI AND GASTROINTESTINAL BIOLOGY
Richard M Peek, Professor
Vanderbilt University, Medical Center, Nashville, Tn 37203-6869
Grant 5R01DK058587-09 from National Institute Of Diabetes And Digestive And Kidney Diseases
Abstract: Chronic gastritis induced by Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, the second leading cause of cancer-related death in the world, yet only a fraction of infected persons ever develop malignancy. Adherence of H. pylori to gastric epithelial cells is critical for induction of gastric injury; therefore, our long-term objective is to investigate the molecular pathways induced by pathogenic H. pylori that lead to epithelial responses with carcinogenic potential. Rodent models have provided valuable insights into the etiologic factors involved in gastric carcinogenesis. However, the infrequency and prolonged time-course required for development of cancer in animal models of H. pylori infection has precluded large-scale analyses that evaluate effects of both pathogen and host in the carcinogenic cascade. Our preliminary studies now demonstrate that a rodent-adapted derivative (7.13) of a human H. pylori strain (B128) rapidly induces gastric cancer in Mongolian gerbils by 4 weeks and in hypergastrinemic (INS-GAS) mice by 24 weeks. Oncogenic H. pylori strain 7.13 binds more avidly to gastric epithelial cells than its parental isolate B128, and using a proteomics-based approach, we have now identified strain-specific membrane-bound proteins expressed by H. pylori strain 7.13, which may contribute to carcinogenesis by functioning as adhesins. A host factor that may mediate aberrant epithelial responses to H. pylori is decay-accelerating factor (DAF), a receptor for chronic pathogens that orchestrates pro-inflammatory epithelial responses. Expression of DAF is increased within H. pylori-infected versus uninfected human gastric tissue, and the intensity of DAF expression is directly related to colonization density and severity of gastritis. We now show that H. pylori adheres more avidly to cells that stably express human DAF compared to vector controls. In vitro and in vivo, H. pylori induces up-regulation of DAF in gastric epithelial cells, and genetic deficiency of DAF attenuates inflammation in H. pylori -infected mice. Our hypothesis is that adherence of H. pylori to gastric epithelial cells activates host signaling pathways that influence carcinogenesis. Our specific aims are 1. To define the bacterial constituents in H. pylori strain 7.13 that mediate carcinogenesis. 2. To define the role of DAF in regulating pathogenic responses to H. pylori in vitro. 3. To define the effect of DAF on H. pylori´-induced injury and carcinogenesis in vivo. This study will help to identify people who are at great risk for stomach cancer. This will greatly improve diagnosis and therapy of H. pylori infections
Keywords: 3-10C; AMCF-I; Address; Adenocarcinoma; Adenoma, Malignant; Adherence; Adherence (attribute); Adhesins, Bacterial; Animal Model; Animal Models and Related Studies; Antigens, CD55; Attenuated; Bacterial Adhesins; Binding; Binding (Molecular Function); Binding Proteins; Biological; Biological Models; Biology; C. pylori; CD55 Antigens; CXCL8; Campylobacter pylori; Cancer Cause; Cancer Etiology; Cancer Induction; Cancer of the Fundus of the Stomach; Cancer of the Gastric Body; Cancer of the Gastric Cardia; Cancer of the Gastric Fundus; Cancer of the Gastric Pylorus; Cancer of the Pylorus of the Stomach; Cancers; Cell Communication and Signaling; Cell Signaling; Cell model; Cells; Cellular model; Cessation of life; Chronic; Chronic Gastritis; Co-culture; Cocultivation; Coculture; Coculture Techniques; Death; Decay-Accelerating Factor; Development; Diagnosis; Doctor of Medicine; E coli; Epithelial; Epithelial Cells; Escherichia coli; Funding; GCP-1; GCP1; Gastric Adenocarcinoma; Gastric Cancer; Gastric Inflammation; Gastric Tissue; Gastric mucosa; Gastritis; Genes; Genetic; Gerbils; H. pylori; H. pylory; H.pylori; Helicobacter Infections; Helicobacter Pylori Infection; Helicobacter pylori; Host Factor; Host Factor Protein; Human; Human, General; IL-8; IL8; IL8 gene; INFLM; In Vitro; Inflammation; Inflammatory; Injury; Integration Host Factors; Intestinal; Intestines; Intracellular Communication and Signaling; Investigators; K60; LECT; LUCT; LYNAP; Lead; Ligand Binding Protein; M.D.; MDNCF; MMPs; MONAP; Malignant Gastric Neoplasm; Malignant Gastric Tumor; Malignant Neoplasms; Malignant Tumor; Malignant Tumor of the Stomach; Malignant neoplasm of stomach; Mammals, Mice; Mammals, Rodents; Man (Taxonomy); Man, Modern; Matrix Metalloproteinases; Mediating; Membrane; Mice; Microbe; Model System; Modeling; Models, Biologic; Molecular; Molecular Interaction; Mucosal Inflammation; Mucositis; Murine; Mus; NAF; Oncogenic; Pathogenicity; Pathway interactions; Pb element; Persons; Programs (PT); Programs [Publication Type]; Proteins; Proteomics; Publications; Receptor Protein; Research; Research Personnel; Researchers; Risk; Risk Factors; Rodent; Rodent Model; Rodentia; Rodentias; Role; SCYB8; Scientific Publication; Severities; Signal Pathway; Signal Transduction; Signal Transduction Systems; Signaling; Stomach; Stomach Adenocarcinoma; Stomach Cancer; TSG-1; Time; Up-Regulation; Up-Regulation (Physiology); Upregulation; adhesin; b-ENAP; base; biological signal transduction; bowel; carcinogenesis; cytokine; density; gastric; gastrointestinal; gene product; heavy metal Pb; heavy metal lead; improved; in vivo; insight; malignancy; malignant stomach neoplasm; membrane structure; microbial; model organism; neoplasm/cancer; pathogen; pathway; programs; receptor; response; social role; tumor; vector control
Project start date: 2000-12-01
Project end date: 2011-06-30
Budget start date: 1-JUL-2010
Budget end date: 30-JUN-2011
5R01DK058587-09 (2010): $305172
5R01DK058587-08 (2009): $308258
5R01DK058587-07 (2008): $308262
2R01DK058587-06A1 (2007): $325524
Richard M Peek
Vanderbilt University
Project start date: 2000-12-01
Project end date: 2017-05-31
MOLECULAR AND CELLULAR BASIS FOR DIGESTIVE DISEASES
Richard M Peek
Vanderbilt University, Medical Center, Nashville, Tn 37203-6869
Grant 3P30DK058404-09S1 from National Institute Of Diabetes And Digestive And Kidney Diseases
Project start date: 2000-12-01
Project end date: 2012-05-31
Budget start date: 1-JUN-2010
Budget end date: 31-MAY-2011
PFA/PA: RFA-DK-06-007
3P30DK058404-09S1 (2010): $99250
Sponsored Links Excellgen http://Excellgen.com
H. Pylori-Induced Inflammation And Gastric Cancer
Richard M Peek, Professor
Medicinevanderbilt University
Grant 1P01CA116087-01A2 from National Cancer Institute IRG: ZCA1
Project start date: 2009-01-01
Project end date: 2013-12-31
H. PYLORI RELATIONSHIP TO DIGESTIVE DISEASES AND CANCER
Richard M Peek, Professor
Vanderbilt University, Medical Center, Nashville, Tn 37203-6869
Grant 5R01CA077955-12 from National Cancer Institute
Keywords: Actins; Address; Adherence; Adherence (attribute); Animal Model; Animal Models and Related Studies; Animals; Apoptosis; Apoptosis Pathway; Apoptotic; Attenuated; Bacterial Gene Proteins; Bacterial Proteins; Biological; Biological Models; C. pylori; Campylobacter pylori; Cancer Cause; Cancer Etiology; Cancer Induction; Cancer of the Fundus of the Stomach; Cancer of the Gastric Body; Cancer of the Gastric Cardia; Cancer of the Gastric Fundus; Cancer of the Gastric Pylorus; Cancer of the Pylorus of the Stomach; Cancers; Cell Communication and Signaling; Cell Culture Techniques; Cell Death, Programmed; Cell Nucleus; Cell Signaling; Cell-Cell Adhesion; Cells; Cessation of life; Complex; Data; Death; Development; Digestive Diseases; Digestive System Diseases; Digestive System Disorders; EGFR; ERBB Protein; ERBB1; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Kinase; Epidermal Growth Factor Receptor Protein-Tyrosine Kinase; Epithelial; Epithelial Cells; Fundic Gland; Funding; Gastric Adenocarcinoma; Gastric Cancer; Gastric Glands; Gastric mucosa; Gene Down-Regulation; Gene Products, Bacterial; Gerbils; Glands, Gastric; Grant; H. pylori; H. pylory; H.pylori; HER1; Helicobacter Infections; Helicobacter Pylori Infection; Helicobacter pylori; Host Factor; Host Factor Protein; Human; Human, General; In Vitro; Inflammatory; Injury; Integration Host Factors; Intracellular Communication and Signaling; Island; Lesion; Link; MMP-7; MMPs; Malignant; Malignant - descriptor; Malignant Gastric Neoplasm; Malignant Gastric Tumor; Malignant Neoplasms; Malignant Tumor; Malignant Tumor of the Stomach; Malignant neoplasm of stomach; Mammals, Mice; Mammals, Rodents; Man (Taxonomy); Man, Modern; Matrilysin; Matrin; Matrix Metalloproteinase-7; Matrix Metalloproteinases; Mediating; Mediator; Mediator of Activation; Mediator of activation protein; Membrane; Mice; Model System; Modeling; Models, Biologic; Mucosa; Mucosal Tissue; Mucous Membrane; Murine; Mus; Nuclear Translocation; Nucleus; Oncogenesis; PUMP-1; Pathogenicity Island; Pathway interactions; Persons; Pre-Malignant; Premalignant; Proteins; Publications; Pylorus; Receptor, EGF; Receptor, TGF-alpha; Receptor, Urogastrone; Receptors, Epidermal Growth Factor-Urogastrone; Risk; Risk Factors; Rodent; Rodent Model; Rodentia; Rodentias; Scientific Publication; Signal Pathway; Signal Transduction; Signal Transduction Systems; Signaling; Stomach; Stomach Adenocarcinoma; Stomach Cancer; System; System, LOINC Axis 4; Time; Trans-Activation (Genetics); Transactivation; Transcription Corepressor; Transcription Repression; Transcription Repressor; Transcription Repressor/Corepressor; Transcriptional Corepressor; Transcriptional Repression; Transcriptional Repressor; Transcriptional Repressor/Corepressor; Transforming Growth Factor alpha Receptor; Up-Regulation; Up-Regulation (Physiology); Upregulation; biological signal transduction; c-erbB-1; c-erbB-1 Protein; cancer risk; carcinogenesis; cytokine; digestive disorder; erbB-1; erbB-1 Proto-Oncogene Protein; erbBl; gastric; gene product; gene repression; high risk; in vivo; insight; malignancy; malignant stomach neoplasm; membrane structure; microbial; model organism; mutant; neoplasm/cancer; pathogen; pathway; precancerous; proto-oncogene protein c-erbB-1; prototype; public health relevance; response; transcription factor; tumor; tumorigenesis
Project start date: 1997-09-30
Project end date: 2013-03-31
Budget start date: 1-APR-2009
Budget end date: 31-MAR-2010
PFA/PA: PA-07-070
5R01CA077955-12 (2009): $351753
Mechanism That Regulate Helicobacter Pylori-induced Beta-caterin Activation
Richard M Peek, Professor
Medicinevanderbilt University
Grant 5R01DK073902-04 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: ZRG1
Keywords: Helicobacter, cell actin, adenocarcinoma, adenoma, cadherin, cancer risk, carcinogenesis, cell adhesion, cytokine, cytoskeleton, death, epithelium, gene, gene expression, gene induction /repression, gerbil /jird, growth factor, growth factor receptor, human, inflammation, injury, lead, lymphocyte, membrane, model, mutant, neoplasm /cancer, phenotype, phosphorylation, protein, receptor, secretion, stomach neoplasm, transcription factor clinical research
Project start date: 2006-04-01
Project end date: 2010-12-31
Richard M Peek, Professor
Vanderbilt University Medical Center Nashville, Tn 372036869
Grant 3T32DK007673-13S1 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: ZDK1
Project start date: 1992-07-01
Project end date: 2008-06-30
3T32DK007673-13S1 (2005): $72010
PATHOGENESIS OF H PYLORI INDUCED GASTRIC INFLAMMATION
Richard M Peek, Professor
Medicinevanderbilt University
medical Center
nashville, Tn 372036869
Grant 1K08DK002381-01A1 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: SRC
Project start date: 1996-07-01
Project end date: 2001-06-30
1K08DK002381-01A1 (1996): $76950