The Center for Pharmacometabolomics at Duke led by Rima Kaddurah-Daouk, PhD, is the coordinating center for Pharmacometabolomics Research Network, which includes over fifteen academic centers. It is also home for the Molecular Psychchiatry Metabolomics Program program where metabolomics is used to map pathways implicated in neuropsychiatric diseases.
The Pharmacometabolomics Research Network is a collaborating network established with funding from NIGMS. Its goal is to integrate the rapidly evolving science of metabolomics with molecular pharmacology and pharmacogenomics to move toward the creation of a new discipline – “Pharmacometabolomics.”This multi-institutional interdisciplinary research consortium involves centers of excellence in metabolomics and metabolomic bioinformatics, together with centers for molecular pharmacologic and pharmacogenomic science that will move beyond focused scientific collaboration to create an environment in which a cooperative, iterative process of hypothesis generation and testing will be applied to achieve the union of metabolomic and pharmacologic science to create pharmacometabolomics. This merge has the potential to accelerate advances in our understanding of mechanisms of drug action and individual variations in drug response.
What is metabolomics?
Metabolomics is the study of metabolism at the global level. It involves systematic study of the "metabolome", the complete repertoire of small molecules present in cells, tissues or organisms. The identities, concentrations and fluxes of these compounds represent the product of interactions that extend from gene sequence to include gene expression, protein expression and the total cellular environment, an "environment" that – in the clinical setting – includes drug exposure. Metabolomics has been identified as an important area for technical development under the NIH Roadmap Initiative. Sophisticated metabolomic analytical platforms and informatics tools have been developed that make it possible to begin the process of defining signatures for disease and for response to drugs used to treat disease (see publications list).
Pharmacometabolomics is the use of the techniques of metabolomics to define metabolomic signals that will provide insight into mechanisms of drug action or mechanisms responsible for individual variation in drug response phenotypes. Those phenotypes can vary from life threatening adverse drug reactions to lack of the desired therapeutic efficacy. Pharmacometabolomics could contribute significantly to our attempts to truly individualize drug therapy.
Pharmacometabolomics and Personalized Medicine
Metabolomic signatures can be determined for patients who do and do not respond to drug therapy or patients who do develop or do not develop metabolic side effects. These signatures could reflect both mechanisms of drug action and variation in the drug response phenotype. Therefore, they can serve as the basis for the generation and testing of mechanistic hypotheses that address the underlying basis for individual variation in drug response –making it possible to move toward a goal of truly “personalized” or “individualized” drug therapy. These contributions will contribute to the process of personalizing treatment where ultimately the right drug is selected for each.