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Name of Submitter:
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John Groopman
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Title of proposed idea:
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Genes and Exposures in Chronic Diseases
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What is the major obstacle/challenge in the biomedical research field? What is needed to overcome this obstacle/challenge?
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Genetic and epigenetic changes are central to the etiology and progression of most chronic diseases in humans. The rapid advancement of technologies such as, deep sequencing, metabolomics and proteomics, permit an exploration of underlying mechanisms at the individual level. Similar technologies for the assessment of the spectrum of exposures that drive these changes in individuals are at a much earlier stage of development. Simply put, there are no high throughput methods similar to what we have for genomic analysis for exposure assessment. Thus, these exposures are most frequently assessed by population-based statistical methodologies. Advancement in the sciences needed to discern specific gene–environment interactions are critically needed. |
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What emerging scientific opportunity is ripe for investment by the Common Fund?
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Over the past 10 years advances in mass spectrometry has resulted in a more than 1000 fold increase in sensitivity to measure chemical, physical and biological agents that people are exposed to and contribute to chronic diseases. These technologies have the requisite sensitivity and specificity but lack high throughput methods and informatics infrastructure that need to be developed and put in place to take advantage of this ability to measure these critical exposures. |
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What are the potential Common Fund investments that could accelerate scientific progress in this field?
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A coalescence of chemical, physical, biological and engineering disciplines need to be brought to bear to break through the impediment to high-throughput analysis of the complex exposures over time that contribute to chronic disease. These investments would include the utilization of the vast number of biological samples of the been collected in a number of long-term longitudinal epidemiological studies of cardiovascular disease, cancer, women's health and immunological dysfunction. Many of these samples have associated outcome data, therefore, this repository is ripe for biomarker discovery and validation. The application of nanotechnologies, micro fluidics and and high sensitivity detectors would greatly accelerate our ability to understand what people are exposed to and how these exposures impact genomic expression in disease development. |
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If a Common Fund program on this topic achieved its objectives, what would be the impact?
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The ability to explore exposures in samples collected from longitudinal studies prior to chronic disease development will reveal critical insights that can be used for the design of individualized prevention strategies in people. While we have made enormous strides in the design of individualized therapies following the diagnosis of the disease, we are still very far from having comparable individualized prevention methods. Since we can fairly accurately predict the continuing rise of many chronic diseases and populations there is a compelling need to develop strategies that can contribute to a flattening of these trajectories. |
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