The research focus of the Zhu lab is on identifying both genetic and environmental factors that impact pharmacokinetics and pharmacodynamics of various therapeutic agents. The Zhu lab is interested in applying this information to guide the personalized use of medications in order to maximize efficacy and minimize the risk of adverse effects. Areas of current research include pharmacogenetics of drug metabolizing enzymes and transporters as well as proteomics and metabolomics as related to personalized medicine.
- Pharmacogenetics of Drug Metabolizing Enzymes and Transporters
Genetic polymorphisms are the major contributing factors to varied expression and activity of drug metabolizing enzymes and transporters, and cause significantly varied responses to pharmacotherapy among individuals. The Zhu laboratory is interested in determining genetic variants associated with interindividual variability of drug metabolizing enzymes and transporters using both basic and clinical approaches. Professor Zhu and his colleagues are among the first demonstrating that some carboxylesterase 1 (CES1) genetic variants can markedly impair the function of CES1, the primary hepatic hydrolase in humans, and significantly alter the pharmacokinetics and pharmacodynamics of drugs metabolized by CES1. He has extended his pharmacogenetic research beyond CES1 to many other clinically important enzymes and transporters. The long-term goal of this line of research is to identify genetic variants that can serve as biomarkers that predict individual responses to specific medications, and to apply this information to the practice of personalized medicine.
- Proteomics and Bioinformatics for the Study of Missing Heritability in Pharmacogenomics
Although studies have identified numerous genetic variants associated with various inheritable traits, these variants can only explain a small proportion of the heritability. This phenomenon is called missing heritability. In the area of pharmacogenomics, missing heritability refers to the fact that genetic variants identified from previous association studies only account for a small fraction of heritable variability in response to pharmacotherapy. Identifying and characterizing those unknown genetic variants that affect the outcomes of drug therapy are fundamental for successful application of pharmacogenomics to personalized medicine. We are utilizing an integrated approach including a novel quantitative proteomic method developed in our lab and bioinformatics to study the effect of genetic variants on gene expression at the protein level. We are expecting that our study will reveal those important regulatory genetic variants that conventional approaches are unable to detect. The study holds great promise for paving the way to solve the “missing heritability” problem and enhancing the utility of pharmacogenomics in clinical practice.