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

Adjunct Professor
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

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.  PMID: 17301735

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.  PMID: 18232020

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.  PMID: 18463198

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. PMID: 20017671

Leeder JS, Kearns GL, Spielberg SP, van den Anker J.  Understanding the relative roles of pharmacogenetics and ontogeny in pediatric drug development and regulatory science.  J Clin Pharmacol 2010;50:1377-1387. PMID: 20150527

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.  PMID: 20191581

Becker ML, Gaedigk R, van Haandel L, Thomas B, Lasky A, Hoeltzel, Dai H-Y, Stobaugh J, Leeder JS.  The effect of genotype on methotrexate polyglutamates variability in Juvenile Idiopathic Arthritis and association with drug response.  Arthritis & Rheumatism 2011; 63: 276-85 PMID: 20954192

Price KE, Pearce RE, Garg UC, Heese BA, Smith LD, Sullivan JE, Kennedy MJ, Bale Jr, JF, Ward RM, Chang TKH, Abbott FS, Leeder JS.  Effects of valproic acid on organic acid metabolism in children:  A metabolic profiling study.  Clin Pharmacol Ther 2011; 89:867-874 PMID:  21544075

Becker ML,van Haandel L, Gaedigk R, Thomas B, Hoeltzel MF, Lasky A, Dai H, Stobaugh J, Leeder JS. Red blood cell folate concentrations and polyglutamate distribution in Juvenile Arthritis: Predictors of folate variability.  Pharmacogenetics Genomics 2012; 22:236-246 PMID: 22344247

Last modified: Dec 26, 2013

Contact

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

Children’s Mercy Hospital
2401 Gillham Road
Kansas City, MO 64108

P: (816) 234-3059
F: (816) 855-1958
sleeder@cmh.edu

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