PAAR4Kids Group – Clinical Implementation of Preemptive Pharmacogenetic Testing.
Preemptive pharmacogenetic tests are being systematically implemented into patient care at St. Jude Children’s Research Hospital. Planned with St. Jude’s Family Advisory Council, the PG4KDS clinical trial protocol (http://www.stjude.org/pg4kds) has enrolled over 1200 patients from May 2011-April 2013, [PMCID: 3589526] using the Affymetrix DMET array [PMCID: 3516299] supplemented with a copy number assay for CYP2D6. One gene/drug pair at a time is selectively migrated into the electronic medical record (EMR) for all enrolled patients.
Two genes and 8 associated drugs are implemented thus far. Prior to migration of a pharmacogenetic test into the EMR, substantial effort is required to create tables (http://www.pharmgkb.org/page/tppTables) that translate diplotypes into phenotypes (working with the TPP), pharmacogenetic diagnoses (working with PHONT), automated clinical interpretation templates, [PMCID: 3589522] interruptive point-of-care prescribing alerts, and patient and clinician educational tools.
Drug prescribing decisions and actionable phenotypes are prioritized and defined by CPIC (http://www.pharmgkb.org/page/cpic), an effort led by PAAR4Kids and PharmGKB.
Within PAAR4Kids, my research interest is to characterize the genetic basis of inter-individual variability in the susceptibility and treatment response of childhood acute lymphoblastic leukemia (ALL).
Primarily via genome-wide association studies (GWAS) in collaboration with the Children’s Oncology Group, we identify genetic variants that contribute to ALL disease risk (J Clin Oncol 30:751) and to treatment outcome (JAMA301:393, Blood 120:4197).
With the overarching goal to reveal novel biology of ALL and to develop more individualized therapy, we also extensively follow up on GWAS hits and functionally characterize molecular mechanisms underlying their associations with leukemogenesis and response to chemotherapy.
We focus on both inherited and acquired genomic variations (also interactions between the two genomes), with a particular emphasis on the genomics of racial disparities in childhood ALL (Nat Genet 43:237).
