Individualized Medicine: Discovery, Translation and Implementation

Pharmacogenomics is a major component of individualized medicine. PGx is to study the contribution of genome to variation in drug response, ranging from severe side effects to lack of efficacy. The tools to study the genome has evolved significantly, allowing us to identify genetic variation in the entire genome and to understand their functional impact on cellular phenotypes as well as clinical phenotypes. PGx is a type of genomic medicine that has been already moving into implementation in the clinic to help physician making therapeutic decision. However, drug response is a complex phenotype involving many factors including individual's host genome, somatic genome (in the case of cancer), demographic information, clinical symptoms etc. To best integrate all of the information, for example, we have applied computational approaches to develop predictive algorithms and clinical decision support tools, in this case, prediction of anti-depressant treatment. On the other hand, increasing emphasis on understanding the function of the genome also stimulate the application of functional genomics and other omics. We also have applied a series of technologies to help understand the contributions of host genome as well as somatic genome in drug response and drug mechanisms of action.

Dr. Wang was trained in a national center for pharmacogenomic (PGx) research that has been engaged in the application of PGx in clinical translational studies for twenty years. She is currently a Professor and the Chair of the Department of Molecular Pharmacology and Experimental Therapeutics. Her has developed a research program with a focus on the use of high throughput genomic technology, joined with a cell-based model system that consists of 300 lymphoblastoid cell lines (LCLs) as well as cancer cell lines with extensive high throughput genomic data to study mechanisms of cancer biology and therapies. Her research has also focused on understanding basic biological pathways and their impact on response to drug therapy. As a Co-PI, she led the functional genomics activities within the Mayo-NIH Pharmacogenomics Research Network (PGRN) grant that included the projects understanding treatment resistance in breast cancer and in depression. She has led functional genomic studies related to many clinical translational studies that helped to identify and understand biomarkers associated with clinical response to therapies. She is also leading a program that is developing patient derived xenografts (PDX) using breast and prostate biopsy samples collected from prospective trials. Therefore, her lab also has substantial experience using PDX and 3D organoids for treatment evaluation and resistance mechanism identification. Dr. Wang is a member of several key programs at Mayo including the Mayo-NIH Comprehensive Cancer Center (MCCC), and she is the Director for the Pharmacogenomics Program of the Mayo Center for Individualized Medicine (CIM). She is also an elected member of the American Society of Clinical Investigation (ASCI).