The broad, long-term objective of this project is to develop a multi-institutional, multi-disciplinary translational Research Center to accelerate the clinical use of targeted imaging methodologies for the early detection and prevention of esophageal adenocarcinoma through the Barrett's Esophagus Translational Research Network (BETRNet). 3 inter-related Primary Research Projects and Shared Research Resources (Cores) will be established to develop advanced endoscopic imaging as an enabling technology for management of patients with Barrett's esophagus by visualizing molecular targets from amplified and overexpressed genes. In Project 1, genomic data will be analyzed to identify molecular targets based on properties of gene amplification and/or overexpression. These targets will be used to select highly specific peptides in Project 2 that will be fluorescent-labeled for detection on imaging. A multi-spectral scanning fiber endoscope will be developed in Project 3 to perform real time visualization of a panel of peptides in 3 fluorescence channels. The unique instrument design can pass through the working channel of a standard medical endoscope to allow for concurrent white light imaging. Future versions of this instrument may have 12 or more channels. Image processing algorithms will developed to """"""""red-flag"""""""" diseased regions on a panoramic view of the distal esophagus. This integrated imaging strategy aims to assist the physician in guiding tissue biopsy of high grade dysplasia and early adenocarcinoma that can not been seen otherwise. Phase 1 studies will be performed to prepare for a future multi-center clinical validation study. Future applications will allow for real time spatial visualization and monitoring of other targets, including those associated with stem cells or with biomarkers of cancer risk. Moreover, imaging of molecular targets can be performed in patients with Barrett's esophagus over time to better understand the molecular mechanisms of this disease. The 3 Cores will support the Primary Research Projects, Pilot Projects, and Cross-BETRNet Projects. The Administrative Core will provide support for grants and regulatory management, including budgets, financial reporting, progress reports, human subjects protocols, investigation of new drug (IND) applications, and Steering Committee representation. The Bioinformatics Core will provide support the Primary Projects for statistical evaluation of genomic, imaging, and clinical data and the BETRNet Network for data sharing and archiving of tissue specimens. The Validation &Pathology Core will provide support for validation of peptide binding activity to amplified and overexpressed gene targets in high-grade dysplasia and early adenocarcinoma.

Public Health Relevance

This research addresses the need for novel methodologies to improve early detection and prevention of esophageal adenocarcinoma in patients with Barrett's esophagus, a disease notable for having the fastest growing incidence of all cancers in the U.S. Targeted imaging provides an enabling technology to guide tissue biopsy and to study molecular mechanisms of cancer transformation over time. More effective cancer preventive measures will benefit not only affected individuals but also the public at large.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
1U54CA163059-01
Application #
8209767
Study Section
Special Emphasis Panel (ZCA1-SRLB-1 (O1))
Program Officer
Richmond, Ellen S
Project Start
2011-09-21
Project End
2016-08-31
Budget Start
2011-09-21
Budget End
2012-08-31
Support Year
1
Fiscal Year
2011
Total Cost
$1,144,545
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Zhou, Juan; He, Lei; Pang, Zhijun et al. (2017) Identification and validation of FGFR2 peptide for detection of early Barrett's neoplasia. Oncotarget 8:87095-87106
Savastano, Luis E; Seibel, Eric J (2017) Scanning Fiber Angioscopy: A Multimodal Intravascular Imaging Platform for Carotid Atherosclerosis. Neurosurgery 64:188-198
Savastano, Luis E; Zhou, Quan; Smith, Arlene et al. (2017) Multimodal laser-based angioscopy for structural, chemical and biological imaging of atherosclerosis. Nat Biomed Eng 1:
Zhou, Quan; Li, Zhao; Zhou, Juan et al. (2016) In vivo photoacoustic tomography of EGFR overexpressed in hepatocellular carcinoma mouse xenograft. Photoacoustics 4:43-54
Joshi, Bishnu P; Wang, Thomas D (2016) Gastrointestinal imaging in 2015: Emerging trends in endoscopic imaging. Nat Rev Gastroenterol Hepatol 13:72-3
Ferrer-Torres, Daysha; Nancarrow, Derek J; Kuick, Rork et al. (2016) Genomic similarity between gastroesophageal junction and esophageal Barrett's adenocarcinomas. Oncotarget 7:54867-54882
Joshi, Bishnu P; Duan, Xiyu; Kwon, Richard S et al. (2016) Multimodal endoscope can quantify wide-field fluorescence detection of Barrett's neoplasia. Endoscopy 48:A1-A13
Joshi, Bishnu P; Zhou, Juan; Pant, Asha et al. (2016) Design and Synthesis of Near-Infrared Peptide for in Vivo Molecular Imaging of HER2. Bioconjug Chem 27:481-94
Sturm, Matthew B; Wang, Thomas D (2015) Emerging optical methods for surveillance of Barrett's oesophagus. Gut 64:1816-23
Jiang, Hui; Salzman, Julia (2015) A penalized likelihood approach for robust estimation of isoform expression. Stat Interface 8:437-445

Showing the most recent 10 out of 40 publications