Barrett's esophagus: pathways and prevention. We have identified three areas in which we can make adifference. The first is investigation of the evolution of clones with acquired epigenetic alterations andgenomic abnormalities to determine the extent to which they and measures of genome instability predictprogression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA). The secondisinvestigation of associations of host and environmental risk and protective factors with measures of instability(telomeres, fragile sites) and clonal evolution to evaluate the extent to which they may modulate progressionfrom BE to EA. The third is to develop robust, clinically compatible biomarker platforms and candidateinterventions to prevent EA that can be used in other centers, multicenter studies and randomized trials toimprove patient care and population health. Each member of the Executive Committee bringscomplementary expertise to the P01 in at least two disciplines, including genetics, cancer biology, biomarkerresearch, epidemiology, aging, evolutionary biology, computational science, biostatistics, andgastroenterology. The Leadership Core is responsible for planning, implementing, evaluating andcoordinating scientific progress at daily, weekly, monthly, and yearly intervals to assure that that the P01achieves its strategic goals. We have established a network of leadership that extends from the ExternalAdvisory Board into each project and core. The Executive Committee meetings are open to everyone in theP01. Study designs, implementation, progress and analysis are all presented and reviewed in regularlyscheduled P01 meetings (average 2.2 per month in the current funding period). The External Advisory Boardwill assemble formally to review the P01 annually as well as informally as appropriate. Project and CoreCoordinators, under the direction of the Project Leaders and Core Directors, will assure timelyimplementation of the decisions of the Executive Committee as well as being a vehicle for early identificationof opportunities and challenges that can be brought to the attention of the Executive Committee.
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