I have performed several retrospective analyses of clinical trial datasets to discover pharmacogenetic, pharmacokinetic, and pharmacometabolomic predictors of paclitaxel-induced peripheral neuropathy and am currently collecting and analyzing larger cooperative group clinical trial cohorts to validate these findings. One ongoing project that I am particularly excited is using our previously published neuropathy prediction model, which includes paclitaxel pharmacokinetics and dosing, and attempting to introduce genetics to explain residual variability in the “neuropathy sensitivity” phenotype. I also have ongoing work in the pharmacogenetics of hormonal treatment in breast cancer. I am currently leading a meta-analysis of all patient cohorts that have tamoxifen pharmacokinetic data and CYP2D6 genetic data to generate an endoxifen prediction algorithm and empirically derive estimates of the percentage activity of individual CYP2D6 alleles. I hope that this project will improve the accuracy of translating CYP2D6 genotype into predicted activity phenotype and produce a percentage phenotypic activity that is more intuitive for clinicians.
He is the co-editor of Pharmacogenomics: Challenges and Opportunities in Therapeutic Implementation (2nd edition), and his notable honors include the 2011 William Bowes Jr Award in Medical Genetics from Partners HealthCare Center for Personalized Genetic Medicine, and the 2012 Dr. Harold and Golden Lamport Research Award from the Icahn School of Medicine at Mount Sinai.
Her primary research interests are in the fields of pediatric cancer, pain, and pharmacogenomics. Dr. Haidar is the program coordinator for St. Jude’s ASHP-accredited PGY2 Clinical Pharmacogenomics Residency and is also an Assistant Professor of Clinical Pharmacy at The University of Tennessee Health Science Center. She is double board certified (BPS) in Pharmacotherapy and Oncology.
We expect to provide a comprehensive view of the ‘CYP3A interactome’, clarifying a substantial portion of CYP3A variability. The goal is to identify the main genetic and non-genetic determinants of CYP3A enzyme activity, with clinical utility as biomarkers guiding drug therapy. The approaches used in this project are broadly applicable to any genes of interest, to dissect complex genomic architecture, gene regulatory networks and discover genetic biomarkers for personalized drug therapy or disease prevention.
Dr. Mushiroda’s team has developed a targeted next generation sequencing (NGS) panel of 100 pharmacogenes related to pharmacokinetics based on multiplex-PCR, which can analyze common and rare variants comprehensively and accurately, and thus will be effective for the identification of PGx biomarkers (https://doi.org/10.18632/oncotarget.25712).
Since his mission is implementation of PGx testing, his team conducts prospective clinical trials to demonstrate the clinical utility of genetic tests using the PGx biomarkers identified by their basic research. If successful, this will lead to use of the PGx biomarkers as in-vitro diagnostics under the health insurance system. Recently, they completed a prospective PGx clinical trial, GENCAT that showed clinical utility of HLA-A*31:01 screening for patients who needed treatment with an antiepileptic drug carbamazepine (https://jamanetwork.com/journals/jamaneurology/article-abstract/2676800).
To tackle the issue of PGx regionally, in 2012 RIKEN established the South East Asian Pharmacogenomics Research Network (SEAPharm) together with five other Asian countries (Korea, Indonesia, Malaysia, Taiwan, and Thailand). Membership has been steadily increasing, with Singapore joining in 2014, and Vietnam in 2016. Last year, SEAPharm accepted three newcomers, Nepal, Laos and the Philippines, on the team. The aim of the collaboration is to identify PGx biomarkers associated with adverse drug reactions, such as skin rash induced by anti-epileptics and antibiotics, and hepatic injury induced by anti-tuberculosis agents. In addition, a new project has been started, which involves targeted NGS of genomic DNA from 1,000 people from 10 countries to clarify the genetic diversity of drug-metabolizing enzymes and drug transporters in Southeast Asian populations.
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