The overall objectives of this BETRNet Translational Research Center (TRC-F) are: 1) to conduct a rigorous, integrated spectrum of transdisciplinary human research in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) 2) to increase the biological understanding of key observations made by our clinical researchers (familial aggregation of BE and EAC, restitution of squamous mucosa after ablation);3) to translate knowledge derived from genetic and physiologic research to solving clinical dilemmas in detection, prognosis, and therapy of BE in order to prevent EAC and improve the outcomes of EAC;4) to foster a transdisciplinary and translational research culture and to effectively expand and enhance scientific research focused on BE and EAC;5) to evaluate research and transdisciplinary programs and to continuously Improve research, productivity and enhance translational implementation. These objectives build and synergize on existing multi-institutional collaborative networks and the considerable clinical, basic science, and translational expertise available at our institutions, focusing on improving the outcomes of patients with BE and EAC. The overarching organization framework for this TRCF proposal is 1) to focus research on understanding the genetic susceptibility, genomic and epigenetic changes that influence the development of BE and EAC;2) to explore the physiologic, transcriptional, and epigenetic factors that lead to durable ablation of BE;and 3) to translate discoveries into applications that improve familial screening, effective detection, molecular prognostication, and durable ablation of BE.

Public Health Relevance

Esophageal adenocarcinoma (EAC) is a rapidly rising public health problem and its prognosis remains poor. Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma but it often goes undetected. The BETRNet TRC-F focuses on genetic, molecular, and physiologic studies that will develop better methods for detecting BE, predicting its progression to EAC, and eradicating BE that is at risk for developing EAC.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA163060-02
Application #
8338823
Study Section
Special Emphasis Panel (ZCA1-SRLB-1 (O1))
Program Officer
Richmond, Ellen S
Project Start
2011-09-26
Project End
2016-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$1,174,448
Indirect Cost
$400,701
Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Venkitachalam, Srividya; Guda, Kishore (2017) Altered glycosyltransferases in colorectal cancer. Expert Rev Gastroenterol Hepatol 11:5-7
Morris, Shelli M; Davison, Jerry; Carter, Kelly T et al. (2017) Transposon mutagenesis identifies candidate genes that cooperate with loss of transforming growth factor-beta signaling in mouse intestinal neoplasms. Int J Cancer 140:853-863
Cummings, Linda C; Thota, Prashanthi N; Willis, Joseph E et al. (2017) A nonrandomized trial of vitamin D supplementation for Barrett's esophagus. PLoS One 12:e0184928
Luebeck, E Georg; Curtius, Kit; Hazelton, William D et al. (2017) Identification of a key role of widespread epigenetic drift in Barrett's esophagus and esophageal adenocarcinoma. Clin Epigenetics 9:113
Krishnamoorthi, Rajesh; Borah, Bijan; Heien, Herbert et al. (2016) Rates and predictors of progression to esophageal carcinoma in a large population-based Barrett's esophagus cohort. Gastrointest Endosc 84:40-46.e7
Curtius, Kit; Wong, Chao-Jen; Hazelton, William D et al. (2016) A Molecular Clock Infers Heterogeneous Tissue Age Among Patients with Barrett's Esophagus. PLoS Comput Biol 12:e1004919
Kendall, Bradley J; Rubenstein, Joel H; Cook, Michael B et al. (2016) Inverse Association Between Gluteofemoral Obesity and Risk of Barrett's Esophagus in a Pooled Analysis. Clin Gastroenterol Hepatol 14:1412-1419.e3
Fecteau, Ryan E; Kong, Jianping; Kresak, Adam et al. (2016) Association Between Germline Mutation in VSIG10L and Familial Barrett Neoplasia. JAMA Oncol 2:1333-1339
Blum, Andrew E; Venkitachalam, Srividya; Guo, Yan et al. (2016) RNA Sequencing Identifies Transcriptionally Viable Gene Fusions in Esophageal Adenocarcinomas. Cancer Res 76:5628-5633
Venkitachalam, Srividya; Revoredo, Leslie; Varadan, Vinay et al. (2016) Biochemical and functional characterization of glycosylation-associated mutational landscapes in colon cancer. Sci Rep 6:23642

Showing the most recent 10 out of 57 publications