Metformin pathways: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics. PMID: 22722338
VKORC1 Asp36Tyr geographic distribution and its impact on warfarin dose requirements in Egyptians. Thromb Haemost. PMID: 23571513
Response to "Doubt about the feasibility of preemptive genotyping". Clin Pharmacol Ther. PMID: 23249779
Clinical Implementation of Pharmacogenetics: More than One Gene at a Time. Clin Pharmacol Ther. PMID: 23598455
Challenges in Implementing Genomic Medicine: The Mayo Clinic Center for Individualized Medicine. Clin Pharmacol Ther. PMID: 23588321
Emerging Transporters of Clinical Importance: An Update from the International Transporter Consortium. Clin Pharmacol Ther. PMID: 23588305
All SNPs Are Not Created Equal: Genome-Wide Association Studies Reveal a Consistent Pattern of Enrichment among Functionally Annotated SNPs. PLoS Genet. PMID: 23637621
First demonstration that brain CYP2D-mediated opiate metabolic activation alters analgesia in vivo. Biochem Pharmacol. PMID: 23623752
Amlodipine--not a significant contributor to clopidogrel non-response? Heart. PMID: 23315611
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).
