Research
Develop statistical and computational tools for physiologically based pharmacokinetic model for drug-drug interaction prediction.

• In-vitro model and data integration
• Animal model and data integration
• Physiology parameteres integration
• Probabilistic rule based DDI prediction assessment
• Bayes scheme for DDI model development

Develop data mining tools for pharmacology information retrieval, and transform them into pharmacokinetics /pharmacodynamics models

• Data mining schemes from abstracts
• Data mining schemes from full texts
• PK compartment model development from non-compartment  model data

Trial simulations and Adaptive Design

• PK/PD and K/PD model development
• Probabilistic assessment in trial simulation
• Adaptive design

Jones D. R., Ekins S., Li L., and Hall S. D. Computational approaches that predict metabolic intermediate complex formation with CYP3A4(+b­­5). 2007 Drug Metab. and Dispos. (in press).

Li L., Yu M., Chin R., Lucksiri A., Flockhart D., and Hall S. Drug-drug interaction prediction: A Bayesian meta-analysis approach. Statistics in Medicine, 2007, 26, 3700 – 3721.

Li L., Hall S., and Desai M. QT Analysis. Encyclopedia of Biopharmaceutical Statistics. 2006. Marcel Dekker.

Li L, Desai M., Desta Z., and Flockhart D. QT analysis: a complex answer to a ‘simple’ problem. Statistics in Medicine, 2004, 23, 2625-2643.

Li L, Lin X, Brown M, Gupta S. and Lee K. A population pharmacokinetic model with time-dependent covariates measured with errors. Biometrics, 2004, 60, 451-460.

Li L, Brown M, Lee K. and Gupta S.  Estimation and inference for a spline-enhanced nonlinear population pharmacokinetic model. Biometrics, 2002; 58, 601-611.

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

Nse, D., Li L., Flockhart D. A., Hayes D. Estrogen receptor genotypes, menopausal status and the lipid effects of  tamoxifen, Journal of Clinical Pharamoclogy and Therapeutics, in press.

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, (in press).

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, 2007, (in press).

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 metabolism in 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.

Wang, G., Wang, X., Li, L., Nephew, N.P., Edenberg, H.J., Zhou, F.C., Liu, Y. Identification of Transcription Factor and microRNA Binding Sites from Array-derived Gene Expression Data, BMC Genomics 2007 (in press).

Wang, X., Wang, G., Shen, C., Li, L., Edenberg, H.J., Sanford, J., Liu, Y., Refining Detection of Protein Binding Regions Using Pyrosequencing-derived RNA Fragments, BMC Genomics 2007 (in press).

Khalili A., Potter D., Yan P., Li L., Gray J., Huang T., Lin S. Gamma-Normal-Gamma Mixture Model for Detecting Differentially Methylated Loci in three cancer cell lines. Cancer Informatics 2007, http://la-press.com/journals.php?pa=toc&journal_id=10&folder_id=15.

Fan M., Yan P. S., Hartman-Frey C., Chen L., Paik H., Abbosh P., Cheng A. S. L, Li L., Huang H. M. T., and Nephew K. Breast cancer cells with acquired resistance to 4-hydroxytamoxifen and fulvestrant display divergent gene expression and DNA methylation signatures. 2006, Cancer Research, 66, 11964-11966

Li L., Cheng A. S. L., Jin V., Paik H. H., Fan M., Li X., Zhang W., Robarge J., Balch K., Davuluri R. V., Kim S., Huang T., Nephew K. A Mixture Model Based Discriminate Analysis for Identifying Ordered Transcription Factor Binding Site Pairs in Gene Promoters Directly Regulated by Estrogen Receptor-a. Bioinformatics, 2006, 22: 2210-2216.

Lim Y., Li L., Desta D., Zhao Q., Rae, J., Flockhart D. A., and Skaar T. Endoxifen, a secondary metabolite of tamoxifen, and 4-OH-tamoxifen induce similar changes in global gene expression patterns in MCF-7 breast cancer cells. Journal of Pharmacology and Experimental Therapeutics, 2006, 318: 502-513.

Shen, C., Li L., and Chen J. A statistical framework to discover true associations from multi-protein complex pull-down proteomics data sets. Proteins: Structure, Function, and Bioinformatics 2006, 64, 436-443.

Li L. Statistical Methods in Bioinformatics – A review. Briefings in Bioinformatics, 2005, 6, 412.

Li L, Shi H, Yiannoutsos C, Huang Tim and Nephew K. Epigenetic hypothesis tests for methylation and acetylation in a triple microarray system. Journal of Computational Biology. 2005, 12, 370-390.