Pharmacogenomics is the study of the role of inheritance in variation in drug response phenotypes, which range from life-threatening adverse drug reactions to lack of the desired therapeutic effect of a drug.
The Mayo Pharmacogenomics Research Program began decades ago with a focus on genetic variation in drug metabolism, particularly "Phase II" conjugation reactions. This emphasis was maintained when the Mayo Clinic NIH-Pharmacogenomics of Phase II Drug Metabolizing Enzymes (PPII) Center was established. However, over the past decade this research program has extended across the entire genome and encompassed all types of genes involved in drug response; including the entire spectrum of pharmacokinetic (PK) and pharmacodynamic (PD) variation.
There is special emphasis on pharmacogenomic studies of breast cancer and other cancers and the pharmacogenomics of depression. The use of genomic data-rich cell line model systems and of large clinical genome-wide association studies (GWAS) have both proven their value in the hands of PPII investigators, especially when joined with functional validation of genetic "SNP signals" and mechanistic pursuit of genes identified during those studies. The clinical GWAS performed by the PPII Pharmacogenomics Research Network (PGRN) Center have involved collaboration with several large clinical trials groups across the United States and Europe and a very productive collaboration with the RIKEN Center for Genomic Medicine in Yokohama, Japan.
Our NIH PGRN Center is applying state-of-the-art genome-wide techniques to discover novel genomic variants that influence response to the therapy of breast cancer and other cancers and depression, always followed by functional and mechanistic pursuit of the genes identified. In addition, systematic efforts to "translate" this new pharmacogenomic information to the bedside are also a significant component of Mayo Clinic PPII PGRN activities.
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