J. Steven Leeder, PharmD, Ph.D.

PharmD, University of Minnesota, 1982

Ph.D., University of Toronto, Canada, 1989

Research Interests

Special Interests: Pediatric clinical pharmacology, pediatric pharmacogenetics, developmental pharmacogenomics

My research interests focus on understanding the relative contributions of genetic variation and ontogeny to observed variability in drug disposition and response in children.  Of particular interest are the changes in drug metabolizing enzyme activities that occur as children mature, the regulatory mechanisms that underlie those developmental changes and the consequences of the developmental changes on drug efficacy and toxicity in children.  For example, urine samples have been obtained from epileptic children being treated with carbamazepine and valproic acid to characterize the relative abundance of metabolites reflecting the activity of competing bioactivation and detoxification pathways, and to determine how these markers change as children grow and develop.  DNA samples from the extremes of the population distributions are utilized to search for gene variants that contribute to the observed variability.  The goal is to identify critical periods of increased bioactivation (potential vulnerability to idiosyncratic adverse drug reactions) to be identified for subsequent prospective investigations.  The pharmacogenetic and –genomic approaches resident within My group provides a rich environment for graduate students to translate their accumulating basic science expertise to clinically important problems.

Selected Publications

Leeder JS, Gaedigk R, Marcucci KA, Gaedigk A, Vyhlidal CA, Schindel BP, Pearce RE.  Variability of CYP3A7 expression in human fetal liver.  J Pharmacol Exp Ther 2005; 314:626-635.

Pearce RE, Uetrecht JP, Leeder JS.  Pathways of carbamazepine bioactivation in vitro II. The role of human cytochrome P450 enzymes in the formation of 2-hydroxyiminostilbene.  Drug Metab Disp 2005; 33: 1819-1826.

Vyhlidal CA, Gaedigk R, Leeder JS.  Nuclear receptor expression in fetal and pediatric liver: Correlation with CYP3A expression.  Drug Metab Disp 2006;34:131-137.

Gaedigk A, Baker DW, Totah RA, Gaedigk R, Pearce RE, Vyhlidal CA, Zeldin DC, Leeder JS.  Variability of CYP2J2 expression in human fetal tissue. J Pharmacol Exp Ther  2006; 319:523-532.

Gaedigk A, Ndjountché L, Divakaran K, Bradford LD, Zineh I, Oberlander TF, Brousseau DC, McCarver GD, Johnson JA, Alander SW, Riggs KW, Leeder JS.  Cytochrome P452D6 (CYP2D6) gene locus heterogeneity: Characterization of gene duplication events.  Clin Pharmacol Ther 2007; 81:242-251.

Blake MJ, Gaedigk A, Pearce RE, Bomgaars LR, Christensen ML, Stowe C, James LP, Wilson JT, Kearns GL, Leeder JS.  Ontogeny of dextromethorphan O- and N-demethylation in the first year of life.  Clin Pharmacol Ther 2007; 81: 510-516.

Gaedigk A, Simon SD, Pearce RE, Bradford LD, Kennedy MJ, Leeder JS.  The CYP2D6 activity score:  Translating genotype information into a quantitative measure of phenotype.  Clin Pharmacol Ther 2008; 83:234-242.

Adjei AA, Gaedigk A, Simon SD, Weinshilboum RM, Leeder JS.  Interindividual variability in acetaminophen sulfation by human fetal liver:  Implications for pharmacogenetic investigations of drug-induced birth defects.  Birth Defects Res A Clin Mol Teratol 2008;82:155-165.

Leeder JS, Pearce RE, Gaedigk A, Modak A, Rosen DI.  Evaluation of a [13C] dextromethorphan breath test to assess CYP2D6 phenotype. J. Clin. Pharmacol 2008; 48:1041-1051
DOI: 10.1177/0091270008319709.

Pearce RE, Lu W, Wang YQ, Uetrecht JP, Correia MA, Leeder JS.  Pathways of carbamazepine bioactivation in vitro. III. The role of human cytochrome P450 enzymes in the formation of 2,3-dihydroxycarbamazepine.  Drug Metab Disp 2008; 36:1637-1649.

Gaedigk A, Fuhr U, Johnson C, Berard A, Bradford LD and Leeder JS. CYP2D7-2D6 hybrid tandems: Identification of novel CYP2D6 duplication arrangements and implications for phenotype prediction. Pharmacogenomics 2010; 11:43-53.

Gaedigk A, Gaedigk R, Leeder JS.  UGT2B17 and SULT1A1 gene copy number variation (CNV) detection by LabChip microfluidic technology. Clin Chem Lab Med 2010; 48:627-33.

Becker ML, van Haandel L, Gaedigk R, Lasky A, Hoeltzel M, Stobaugh J, Leeder JS.  Analysis of intracellular methotrexate polyglutamates in Juvenile Idiopathic Arthritis: Effect of route of administration upon intracellular methotrexate polyglutamate variability.  Arthritis & Rheumatism 2010;62:1803-1812.

Contact Information

J. Steven Leeder, Pharm. D., Ph.D.

Professor of Pediatrics and Pharmacology
Chief, Division of Clinical Pharmacology and Medical Technology

Children’s Mercy Hospital

Division of Pediatric Pharmacology and Medical Technology

2401 Gillham Road

Kansas City, MO. 64108

Phone: (816) 234-3059

Fax: (816) 855-1958
Email: sleeder@cmh.edu

Updated 11/12/11