Membrane transporters and drug development: relevance to pharmacogenomics, nutrigenomics, epigenetics, and systems biology.

The study of membrane transporters may result in breakthroughs in the discovery of new drugs and the development of safer drugs. Membrane transporters are essential for fundamental cellular functions and normal physiological processes. These molecules influence drug absorption and distribution and play key roles in drug therapeutic effects. A primary goal of current research in drug discovery and development is to fully understand the interactions between transporters and drugs at both the system levels in the human body and the individual level for personalized therapy. Systematic studies of membrane transporters will help in not only better understanding of diseases from the systems biology point of view but also better drug design and development. The exploration of both pharmacogenomics and systems biology in transporters is necessary to connect individuals' genetic profiles with systematic drug responses in the human body. Understanding of gene-diet interactions and the effects of epigenetic changes on transporter gene expression may help improve clinical drug efficacy. The integration of pharmacogenomics, nutrigenomics, epigenetics, and systems biology may enable us to move from disease treatment to disease prevention and optimal health. The key issues in such integrative understanding include the correlations between structure and function, genotype and phenotype, and systematic interactions among transporters, other proteins, nutrients, drugs, and the environment. The exploration in these key issues may ultimately contribute to personalized medicine with high efficacy but less toxicity.