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PPII Profile

Pharmacogenetics of Phase II Drug Metabolizing Enzymes

Abstract (Updated, February 2013)

Pharmacogenomics is the study of the role of inheritance in variation in drug response phenotypes, phenotypes that range from life-threatening adverse drug reactions at one end of the spectrum to lack of the desired therapeutic effect of the drug at the other. Pharmacogenomic research includes studies that range from discovery to translation to clinical implementation.

The Mayo Pharmacogenomics Research Network (PGRN) Pharmacogenetics of Phase II Drug Metabolizing Enzymes (PPII) research program originally focused on genetic variation in drug metabolism, particularly Phase II, conjugation reactions. However, since the origin of the PGRN, this research program has expanded to extend across the genome and now encompasses all types of genetic variation that contribute to drug response, including the entire spectrum of genes involved in pharmacokinetic (PK) and pharmacodynamic (PD) variation.

The Mayo PGRN places special emphasis on pharmacogenomic studies of breast cancer and other cancers and on the pharmacogenomics of depression. The use of genomic data-rich cell line model systems, especially the Human Variation Panel of 300 lymphoblastoid cell lines (LCLs) from three ethnic groups, and of large clinical genome-wide association studies (GWAS) (e.g., over 14,000 DNA samples from breast cancer patients) have both proven their value in the hands of PPII investigators. This PGRN Center also always attempts to move beyond biomarkers to the functional validation of genomic SNP signals and pursuit of the mechanisms of genes identified during pharmacogenomic studies. This approach has resulted in the identification, functional validation and mechanistic study of a series of novel genes that play a role in variation in response to antineoplastic therapy. A similar approach has been taken in our studies of SSRI response during the treatment of depression, but those studies have also included pioneering work in which pharmacometabolomics has been used to inform pharmacogenomics, and the use of iPS cells from depressed patients to generate serotonergic neurons for use as a cellular model system. Clinical GWAS performed by the PPII PGRN Center have involved collaborations with several large clinical trials groups across the United States and Europe as well as a highly productive collaboration with the RIKEN Center for Genomic Medicine in Yokohama, Japan. In addition, the Mayo PPII PGRN Center has acted as a catalyst for the clinical implementation of pharmacogenomics throughout the Mayo Clinic a large, multisite academic medical center.

In summary, the Mayo Clinic NIH PPII PGRN Center is applying state-of-the-art genome-wide techniques and Next Generation DNA sequencing and the use of cellular model systems to discover novel genomic variants that influence response to the therapy of cancer and depression, always followed by functional and mechanistic pursuit of the genes identified. Another major component of PPII activities involves the systematic translation and implementation of pharmacogenomics at the bedside.

PPII Team

Mayo Clinic College of Medicine
Richard M. Weinshilboum, MD
Principal Investigator
Email: Weinshilboum.richard@mayo.edu
Phone: (507) 284-2246
Liewei Wang, MD, PhD
Principal Investigator
Email: Wang.liewei@mayo.edu
Phone: (507) 284-5264
Eric Wieben, PhD
Co-Principal Investigator
Email: Wieben.eric@mayo.edu
Phone: (507) 284-3708
Christopher Chute, MD, DPH
Co-Investigator
Email: Chute.christopher@mayo.edu
Phone: (507) 284-5506
Julie Cunningham, PhD
Co-Investigator
Email: Cunningham.julie@mayo.edu
Phone: (507) 238-6863
Matthew Goetz, MD
Co-Investigator
Email: goetz.matthew@mayo.edu
Phone: (507) 284-4857
James Ingle, MD
Co-Investigator
Email: Ingle.james@mayo.edu
Phone: (507) 284-7912
Jean-Pierre Kocher, PhD
Co-Investigator
Email: Kocher.jeanpierre@mayo.edu
Phone: (507) 538-8315
Joanna Biernacka, PhD
Co-Investigator
Email: Biernacka.Joanna@mayo.edu
Phone: (507) 538-5274
Krishna Kalari, PhD
Co-Investigator
Email: Kalari.Krishna@mayo.edu
Phone: (507) 538-4602
Celine Vachon, PhD
Co-Investigator
Email: Vachon.celine@mayo.edu
Phone: (507) 284-9977
Daniel Hall-Flavin, MD
Co-Investigator
Email: flavin.daniel@mayo.edu
Phone: (507) 284-2132
Hu Li, PhD
Co-Investigator
Email: Li.Hu@mayo.edu
Phone: (507) 293-1182

 

 

 

Case Western Reserve University
Vivien Yee, PhD
Co-Investigator
Email: vivien.yee@case.edu
Phone: (216) 368-1184
 
 
 
Harvard Medical School
Paul Goss, MD
Co-Investigator
Email: pgoss@partners.org
Phone: (617) 724-3118
 
 
 
MD Anderson Cancer Center
Aman Buzdar, MD
Co-Investigator
Email: abuzdar@mdanderson.org
Phone: (713) 792-2817
 
 
 
Memorial Sloan Kettering Cancer Center
Mark E. Robson, MD
Co-Investigator
Email: robsonm@MSKCC.ORG
Phone: (212) 434-5129
 
 
 
University of Erlangen
Peter Fasching, MD
Co-Investigator
Email: Peter.Fasching@uk-erlangen.de
Phone: 9131 85 33508
 
 
 
Washington University
Matthew Ellis, MD
Co-Investigator
Email: mellis@dom.wustl.edu
Phone: (314) 362-8903
 
 
 
Secretary or Assistant, for contact purposes:
Luanne Wussow
Assistant
Email: Wussow.luanne@mayo.edu
Phone: (507) 284-2790