Research

Develop statistical methods to analyze genotype/phenotype associations in pharmacogenetics studies and study design

• Functional and genetic variation annotation development for metabolic enzymes, transports, and receptors.
• Gene/gene and gene/environmental interaction with functional genetic polymorphisms
• Structure equation model based pathway analysis
• Adaptive design for pharmacogenetics studies

Identify novel regulation factors and genetic polymorphisms for drug metabolism from public domain databases

Genome-wide association studies for pharmacogenomics studies

Software and Databases

CYP, UGT, NAT
http://galien.pha.ulaval.ca/alleles/alleles.html
nomenclature
http://louisville.edu/medschool/pharmacology/NAT.html
http://www.cypalleles.ki.se/
http://drnelson.utmem.edu/CytochromeP450.html
DrugBank bioinformatics data bases for drugs
http://redpoll.pharmacy.ualberta.ca/drugbank/
Haplo.stats haplotype/phenotype association (score test)
http://mayoresearch.mayo.edu/mayo/research/schaid_lab/index.cfm
Haploview LD and haplo block analysis
http://www.broad.mit.edu/mpg/haploview/index.php
Mixture Model functional-genotype/phenotype association
PHASE Haplotype Estimation
http://stephenslab.uchicago.edu/software.html
PharmGKB Pharmacogenetics Network and Knowledge Base
http://www.pharmgkb.org/
SNPselector SNP selection and power/sample size calculation

Selected Publications
Borges S., Desta Z., Jin Y., Faouzi A., Robarge JD., Philip S., Nguyen A, Stearns V., Hayes D., Rae JM, Skaar TC, Flockhart DA, Li L. A Composite Functional Genetic and Co-Medication CYP2D6 Activity Score In Predicting Tamoxifen Drug Exposure Among Breast Cancer Patients. Journal of Clinical Pharmacology, 2010, 450-458.

Li L., Borges-Gonzales S, Robarge J., Sheng C., Desta Z., and Flockhart D. A Penalized mixture model approach in genotype/phenotype association analysis for quantitative phenotype. Cancer Informatics, 2010, 9, 93-103

Miao J., Jin Y., Marunde R.L., Kim S., Quinney S., Radovich M., Li L., and Hall S.D.  Association of Genotypes of the CYP3A Cluster with Midazolam Disposition In Vivo. Pharmacogenomics Journal, 2009, 9, 319-326.

Srinivasan B.S., Chen J.,  Cheng C., Conti D., Duan S, Fridley BL, Gu X., Haines JL, Jorgenson E., Kraja A., Lasky-Su J., Li L, Wang D., Rodin A, Province M., and  Ritchie M.D. Methods for analysis in pharmacogenomics: Lessons from the Pharmacogenetics Research Network (PGRN) Analysis Group. Pharmacogenomics Journal, 2009, 10, 243-251.

Li L., Yu M., Robarge J., Gao S., Jin Y., Borges-Gonzales S., Nguyen A., Skaar T., Desta Z., McLeod H., Sweeney C J., and Flockhart D. A penalized mixture model approach in gene-gene and gene-environmental interactions for binary phenotypes. Journal of Biopharmaceutical Statistics 2008, 18, 1150-1177.

Li L, Hui S, Desta Z, Todd S, Nguyen A and Flockhart D. Estimating a positive false discovery rate for variable selection in pharmacogenetic studies. Journal of Pharmaceutical Statistics, 2007, 17, 883-902.

Robarge J. D., Li L., Desta Z., Nguyen A., and Flockhart D. A. Evaluating genetic nonmenclature of drug metabolizing enzyme. Journal of Clinical Pharmacology and Therapeutics, 2007, 82, 244-248.

Desta Z., Saussele T., Ward B., Blievernicht J., Li L., Klein K., Flockhart D A., Zanger M. U. Impact of CYP2B6 polymorphism on efavirenz metabolismin vitro. Pharmacogenomics. 2007, 8, 547-558.

Borges-Gonzulas S., Desta Z., Li L., Skaar, T., Ward B., Nguyen A., Jin Y., Storniolo M., Nikoloff M., Koch W., Hayes D., Stearns V., and Flockhart D. Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatment. Clinical Pharmacology and Therapeutics 2006, 80, 61-74.

Jin Y, Desta Z, Stearns V., Ward B., Ho H., Lee J., Skaar T., Storniolo A. M., Li L., Araba A., Blanchard R., Nguyen A., Ullmer L., Hayden J, Lemler S., Weinshilboum R. M., Rae J. M., Hayes D. F., Flockhart D. A. Effects of CYP2D6 Genotype and Antidepressants on Tamoxifen Metabolism During Adjuvant Breast Cancer Treatment. Journal of National Cancer Institute. 2005, 97, 30-39.