The University of British Columbia

About the Principal Investigator

	E-mail: riggskw@interchange.ubc.ca Phone: 604-822-2061 Fax: 604-822-3034

Training

Previous Positions

Current Position

Major Awards

About the Group

Research in my group is primarily focused in the following areas:

• The role of pharmacogenetics/genomics in drug metabolism and toxicity of anticancer drugs in leukemia and breast cancer patients
• The role of pharmacogenetics/genomics in testosterone metabolism and relationship to prostate cancer
• In vitro drug metabolism in cell fractions and intact cell systems
• Pharmacokinetic studies in patients and experimental models
• Drug analysis (HPLC; GC-MS; LC-MS)

Ongoing studies are examining the pharmacokinetics of various SSRIs in the treatment of pre- and post-partum depression and the effect of prenatal exposure on infant bio behaviour. This work is being carried out in collaboration with Dr. Tim Oberlander in the Department of Pediatrics (UBC, Faculty of Medicine) and Dr. Shaila Misri in the Department of Psychiartry at St. Paul’s and B.C. Women Hospital (UBC, Faculty of Medicine). The development of drug metabolizing capability from birth to one year of life is also being investigated in experimental models. This work is being conducted with Dr. Dan Rurak in the Department of Obstetrics and Gynaecology (UBC, Faculty of Medicine). Another major component of my research involves extensive collaborator with Drs. Ron Reid (UBC, Faculty of Pharmaceutical Sciences) and Tom Grigliatti (UBC, Department of Zoology) to study the effects of single nucleotide polymorphisms in enzymes responsible for the metabolism of anthracycline drugs following the expression of various human reductase genes in insect and bacterial cell systems. These studies have been extended to examine these genetic variations in leukemia and breast cancer patients in partnership with Dr. Donna Hogge at the BC Cancer Agency. The effect of these genetic variations in prostate cancer development and progression is also being studied with Dr. Martin Gleave (Department of Urology, UBC, Faculty of Medicine). Drs. Joanna Lubieniecka and Randy Mottus (UBC, Department of Zoology) are also integral partners in this pharmacogenetic/genomic research.

Training Environment

Students in our group are exposed to a very collaborative learning environment in association with research advisors and research associates in Pharmaceutical Sciences, the Department of Zoology or Department of Obstetrics and Gynaecology.  Experimental studies are conducted in a particular department depending on equipment needs and available expertise at each site.  Lab meetings are held on a regular basis where students are expected to present regular updates on their research findings.  Students are challenged to think in detail about their research and its interpretation/limitations.  An emphasis is placed on the development of critical thinking skills and the ability to independently design research studies and protocols to support a given project.

Projects

The role of enzyme single nucleotide polymorphisms in the metabolism of anthracyclines.

The anthracyclines are commonly used in the treatment of various cancers.  A current limitation to the use of these agents, however, is the risk of the development of potentially life threatening cardiotoxicity. There is considerable variability in the therapeutic and toxic responses of cancer patients to these drugs (e.g. doxorubicin), which cannot be explained by known clinical parameters. It is our hypothesis that differences in metabolic activity of enzyme responsible for the metabolism of these drugs may be one of the primary factors underlying this inter-patient variation in drug response. To assess this, we are examining the effect of single nucleotide (SNP) polymorphic variation in the genes coding for the metabolism of doxorubicin and daunorubicin and their potential to alter the concentrations of the parent drug and their respective alcohol metabolites.  Human polymorphic reductase genes (AKR, CBR) are being cloned into insect and bacterial cells lines and cytosolic, microsomal and purified enzymes fractions are being used to assess the in vitro metabolic capacity of these enzymes compared to the wild-type.  Clinical studies have also been initiated in an attempt to correlate identified SNPs that significantly alter drug metabolizing capability with the development of cardiotoxicity in patients receiving either doxorubicin or daunorubicin therapy.  The role of genetic variations in AKRs in the development and progression of prostate cancer is also being assessed in patient studies. (Funded by CIHR)

Biobehavioral pain reactivity in infants at 6 months of age following prenatal psychotropic medication exposure.

This collaborative study is assessing acute pain reactivity and arousal regulation in infants with prolonged prenatal exposure to serotonin reuptake inhibitors (e.g. fluoxetine, paroxetine, sertaline, venlafaxine, citalopram) that are commonly used in the treatment of pre- and post-partum depression. Previous data from our group have demonstrated a blunted acute pain response at birth and at 2 months of age in infants with prolonged SSRI exposure. These assessments are now being extended to infants at 3 and 6 months of age. We are also studying the possible influence of maternal and infant pharmacogenetic factors (metabolic enzymes, 2D6, 2C9, 2C19) on infant exposure to these drugs. These studies are being assessed in comparison to two control groups (infants of depressed mothers who are non medically treated and infants of healthy mothers). (Funded by CIHR)

Development of drug metabolizing capability with age.

It is known that infants born prematurely experience developmental delays and it is hypothesized that their response to drugs may be altered.  In support of this we are examining the pharmacokinetics of drug metabolizing activity in an experimental model from birth to one year of life.

Selected Publications

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