The current application is specifically designed to """"""""integrate"""""""" Metabolomics and Pharmacogenomics to achieve a deeper understanding of the drug-response phenotype and to accelerate the establishment of genotype-phenotype correlations for drug response. Metabolomics is the study of metabolism at the """"""""global"""""""" level and involves studies of the """"""""metabolome"""""""", the entire repertoire of small molecules present in cells and/or tissues. The identities, concentrations and fluxes of these compounds represent the final product of interactions among gene sequence, gene expression, protein expression and the cellular environment, an """"""""environment"""""""" that - in the clinical setting - includes drug exposure. Metabolomics has been identified as an important area for development under the NIH Roadmap Initiative. Pharmacogenomics is the study of the role of inheritance in individual variation in the drug response phenotype - with serious adverse drug reactions at one end of that phenotypic spectrum and lack of the desired therapeutic effect at the other. We believe that the inclusion of Metabolomic data as an additional, and highly informative """"""""intermediate phenotype"""""""" might significantly enhance our ability to understand and predict individual variation in response to therapeutic agents. We propose to test that hypothesis by adding Metabolomic analyses to ongoing Pharmacogenomic studies already funded by the NIH. Collaborating Metabolomics-Pharmacogenomics research teams will test the hypothesis that the application of Metabolomics might identify """"""""signatures"""""""" uniquely related to the drug response phenotype, using representatives of two important drug classes, an HMG CoA reductase inhibitor (simvastatin) and a specific serotonin reuptake inhibitor (escitalopram). The proposed effort to join Metabolomics and Pharmacogenomics represents an ideal example of """"""""Integrative and Collaborative Approaches to Research"""""""". ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Resource-Related Research Projects (R24)
Project #
1R24GM078233-01
Application #
7130276
Study Section
Special Emphasis Panel (ZRG1-BST-R (50))
Program Officer
Okita, Richard T
Project Start
2006-12-14
Project End
2010-11-30
Budget Start
2006-12-14
Budget End
2007-11-30
Support Year
1
Fiscal Year
2007
Total Cost
$573,897
Indirect Cost
Name
Duke University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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Rotroff, D M; Shahin, M H; Gurley, S B et al. (2015) Pharmacometabolomic Assessments of Atenolol and Hydrochlorothiazide Treatment Reveal Novel Drug Response Phenotypes. CPT Pharmacometrics Syst Pharmacol 4:669-79
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Huang, Lingkang; Zhang, Hao Helen; Zeng, Zhao-Bang et al. (2013) Improved Sparse Multi-Class SVM and Its Application for Gene Selection in Cancer Classification. Cancer Inform 12:143-53
Motsinger-Reif, Alison A; Zhu, Hongjie; Kling, Mitchel A et al. (2013) Comparing metabolomic and pathologic biomarkers alone and in combination for discriminating Alzheimer's disease from normal cognitive aging. Acta Neuropathol Commun 1:28
Zhu, Hongjie; Bogdanov, Mikhail B; Boyle, Stephen H et al. (2013) Pharmacometabolomics of response to sertraline and to placebo in major depressive disorder - possible role for methoxyindole pathway. PLoS One 8:e68283

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