The research of Liewei Wang, M.D., Ph.D., is focused on pharmacogenomics, a critical component of individualized medicine that studies the role of inheritance in variation in drug response. Patients treated with the same dose or regimen of a drug can display different responses, ranging from lack of efficacy to severe toxicity.
Dr. Wang's laboratory uses various high-throughput "omics" tools, including genomics, transcriptomics and metabolomics, to identify biomarkers that can help predict clinical response. At the same time, her lab uses various models, including cells, patient-derived xenografts and patient samples, to validate and understand the biology underlying these biomarkers.
- Pharmacogenomics of anti-cancer treatment. Dr. Wang's research team has developed a series of cell line systems, together with a drug cytotoxicity phenotype on each line. They use these cells to perform correlation studies between omics data and cytotoxicity phenotypes for more than a dozen common chemotherapies, targeted therapies and immunosuppressants. This information may help generate pharmacogenomics hypotheses for research in developing drug response bio markers, and may also contribute to understanding mechanisms of drug actions and variation in drug response.
- Clinical genome-wide association studies (GWASs). Dr. Wang's lab performs breast cancer pharmacogenomics clinical GWASs, with a focus on hormonal treatment in prevention and adjuvant settings as well as chemotherapy in both neoadjuvant and adjuvant settings. These biomarkers help to predict both common side effects and efficacy. The biomarkers are then subjected to intensive functional characterization in the lab using cells and animal models to help understand the mechanisms by which these biomarkers might contribute to variation in drug response.
- Translational pharmacogenomics and implementation pharmacogenomics. An additional area of focus includes research for the BEAUTY study (a breast cancer study) and PROMOTE (a prostate cancer study), both of which are supported by the Mayo Center for Individualized Medicine. The studies involve using next-generation sequencing of tumor and germ line DNA and tumor RNA to identify genomic signatures that might predict resistance to standard therapy and contribute to the development of further treatment regimens to overcome resistance and achieve better outcomes. Dr. Wang's lab supports both studies by using biopsy or surgical samples obtained before and after standard therapy to create patient-derived xenografts. These models can be used for future drug screening and development as well as help to understand resistance mechanisms.
Significance to patient care
Pharmacogenomics is a major component of individualized medicine. Every patient is unique in her or his response to treatment; one size does not fit all. Therefore, identifying patients' responses ahead of time could help achieve better therapeutic effect, minimize drug-induced toxicity and offer cost-saving benefits.
- Mayo Graduate School Distinguished Alumni, 2014
- ASPET-Astellas Award in Translational Pharmacology, The American Society for Pharmacology and Experimental Therapeutics, 2007
- Edward C. Kendall Mayo Clinic Alumni Association Research Award, Mayo Clinic, 2005