Pharmacogenomics research is aimed to unravel biological basis of inter-patient variability in drug efficacy and toxicity. This overarching objective has guided our laboratory programs in the past 30 years.
Early work in the 1990’s led by Drs. Evans and Relling discovered TPMT variants as the genetic causes for thiopurine toxicity in children with acute lymphoblastic leukemia (ALL). This was one of the first pharmacogenetic variants linked to anti-cancer drug toxicity, and TPMT-guided thiopurine dosing served as a model for genetics-driven precision medicine. In the ensuing years, our investigators have stayed at the forefront of pharmacogenomic discovery research, particularly in pediatric cancer patients. Our work uncovered NUDT15 as a second clinically actionable pharmacogenetic factor driving thiopurine toxicity, resulting in changes in FDA drug label and clinical implementation in globally diverse populations. We continue to focus on pediatric cancer drug therapy and our ongoing work examines pharmacogenomics of a wide variety of anti-cancer drugs, especially molecularly targeted agents.