Esophageal Cancer from Cells to Population: A Multiscale Approach The goal of the proposed research is to reduce the burden of esophageal adenocarcinoma (EAC) by optimizing surveillance of patients with Barrett's esophagus (BE) using cutting-edge endoscopic imaging and advanced epigenetic profiling of neoplastic tissues in combination with standard endoscopic techniques. To accomplish this goal we will establish a multidisciplinary collaboration between cancer biologists, epidemiologists, clinicians and computational and mathematical modelers. This research team will develop a multiscale modeling framework that synthesizes and integrates data generated from diverse sources and at different scales to provide a coherent and informative portrayal of the natural history of EAC. Simulation models of EAC actively supported by the NCI's CISNET (U01 CA152926) and data from the Barrett's Esophagus Translational Research Network (BETRNet, U54 CA163060) will serve as the foundation for a new biologically-motivated Multiscale Esophageal Adenocarcinoma Model (MEMo). This new model will be informed by data that span numerous scales including: molecular level DNA methylation data, cellular level volumetric laser endomicroscopy (VLE) data, patient level endoscopic surveillance data, and population level cancer registry SEER data. We will use MEMo as an analytic tool to assess the clinical effectiveness of BE surveillance protocols for early esophageal neoplasia detection and prevention. By the end of the award period, we will have an improved and more comprehensive understanding of the biological and natural history of EAC that provides a platform to design better strategies to control its population burden.
The proposed research is relevant to public health because the goal of this project is to reduce esophageal adenocarcinoma (EAC) mortality and improve the understanding of cancer progression. This goal will be accomplished in a collaboration between NCI's CISNET and BETRNet investigators to narrow the gap between biomechanistic cell-level information related to the neoplastic progression in Barrett's Esophagus (BE) and population-level presentation of EAC. Thus the proposed research is in line with the NIH/NCI's mission to improve fundamental knowledge that will reduce the burden of cancer and its associated morbidity.
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|Leggett, Cadman L; Gorospe, Emmanuel C; Chan, Daniel K et al. (2016) Comparative diagnostic performance of volumetric laser endomicroscopy and confocal laser endomicroscopy in the detection of dysplasia associated with Barrett's esophagus. Gastrointest Endosc 83:880-888.e2|
|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|
|Kaz, Andrew M; Wong, Chao-Jen; Varadan, Vinay et al. (2016) Global DNA methylation patterns in Barrett's esophagus, dysplastic Barrett's, and esophageal adenocarcinoma are associated with BMI, gender, and tobacco use. Clin Epigenetics 8:111|
|Bansal, Ajay; Gupta, Vijayalaxmi; Wang, Kenneth (2016) MicroRNA Expression Signatures During Malignant Progression From Barrett's Esophagus. J Cell Biochem 117:1288-95|
|Chan, Daniel K; Leggett, Cadman L; Wang, Kenneth K (2016) Diagnosing gastrointestinal illnesses using fecal headspace volatile organic compounds. World J Gastroenterol 22:1639-49|
|Curtius, Kit; Hazelton, William D; Jeon, Jihyoun et al. (2015) A Multiscale Model Evaluates Screening for Neoplasia in Barrett's Esophagus. PLoS Comput Biol 11:e1004272|
|Yu, Ming; O'Leary, Rachele M; Kaz, Andrew M et al. (2015) Methylated B3GAT2 and ZNF793 Are Potential Detection Biomarkers for Barrett's Esophagus. Cancer Epidemiol Biomarkers Prev 24:1890-7|
|Kaz, Andrew M; Grady, William M; Stachler, Matthew D et al. (2015) Genetic and Epigenetic Alterations in Barrett's Esophagus and Esophageal Adenocarcinoma. Gastroenterol Clin North Am 44:473-89|
|Inadomi, John M (2015) Cost considerations in implementing a screening and surveillance strategy for Barrett's oesophagus. Best Pract Res Clin Gastroenterol 29:51-63|
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