Curtis D. Klaassen, Ph.D.

 

Ph.D., University of Iowa, 1968

Curriculum Vitae

Research Interests

Toxicology, biliary drug excretion, transgenic animals, gene expression, drug development to prevent and treat liver disease.

Research in this laboratory is involved in basic regulatory mechanisms in toxicology. Our research has three main aims: (1) to determine the role of cellular membrane transporters in the toxicity of chemicals, (2) to determine cellular pathways that can prevent and repair cellular injury, and (3) from this basic knowledge develop drugs to treat diseases in humans. In these projects we are investigating the role that ligand-activated transcription factors play in regulating chemical elimination, examining both transport and biotransformation of chemicals.

All organisms are exposed to foreign chemicals (xenobiotics). Xenobiotics are natural ingredients in food, fungal toxins in food, as well as man-made chemicals, such as drugs, pesticides, and industrial chemicals. Many of these chemicals are lipid soluble and are biotransformed into more water soluble chemicals. The water soluble metabolites must be exported out of cells, into urine, or bile. A number of xenobiotics increase the biotransformation of chemicals by increasing the transcription of biotransformation enzymes, by binding to various transcription factors, such as PXR, CAR, AhR, PPARa and Nrf2.

Our laboratory is involved in determining whether these nuclear receptors not only enhance the biotransformation of chemicals, but also the transport of their metabolites into bile and urine. This would enhance the elimination of xenobiotics. These nuclear receptors regulate not only the excretion of chemicals, but also help to prevent cellular injury and repair. Thus we are attempting to use this knowledge to develop drugs that can be used to treat various diseases.

Models used in our laboratory include knock-out mice, and techniques include surgery, enzyme assays, histology, mRNA analysis by northern blotting and bDNA, western blotting, pharmacokinetics, immunohistochemistry, EMSA, etc.

Selected Publications

Petrick, J.S. and Klaassen, C.D.:  Importance of hepatic induction of constitutive androstane receptor (CAR) and other transcription factors that regulate xenobiotic metabolism and transport.  Drug Metab. Dispos.  35:1806-1815, 2007.  PMID: 17627975

Maher, J.M., Dieter, M.Z., Aleksunes, L.M., Slitt, A.L., Guo, G., Tanaka, Y., Scheffer, G.L., Chan, J.Y., Manautou, J.E., Chen, Y, Dalton, T.P., Yamamoto, M., and Klaassen, C.D.: Oxidative and electrophilic stress induces multidrug resistance-associated protein transporters via the nuclear factor-E2-related factor-2 transcriptional pathway. Hepatology 46: 1597-1610, 2007.  PMID: 17668877

Knight, T.R., Choudhuri, S. and Klaassen, C.D.:  Constitutive mRNA expression of various glutathione S-transferase isoforms in different tissues of mice.  Toxicol. Sci. 100: 513-524, 2007.  PMID: 17890767

Cheng, X., Buckley, D. and Klaassen, C.D.:  Regulation of hepatic bile acid transporters Ntcp and Bsep expression.  Biochem. Pharmacol. 74: 1665-1676, 2007.  PMID: 17897632

Tanaka, Y., Chen, C., Maher, J.M. and Klaassen, C.D.:  Ischemic-reperfusion of rat livers decreases liver and increases kidney multidrug resistance-associated protein 2 (Mrp2).  Toxicol. Sci. 101: 171-178, 2008.  PMID: 17959626

Lu, H., Choudhuri, S., Ogura, K., Csanaky, I.L., Lei, X., Cheng, X., Song, P., and Klaassen, C.D.:  Characterization of organic anion transporting polypeptide 1b2-null mice: essential role in hepatic uptake/toxicity of phalloidin and microcystin-LR.  Toxicol. Sci. 103: 35-45, 2008.  PMID: 18296417

Cheng, X. and Klaassen, C.D.:  Perfluorocarboxylic acids induce cytochrome p450 enzymes in mouse liver through activation of PPAR{alpha} and CAR transcription factors.  Toxicol. Sci. 106: 29-36, 2008.  PMID: 18648086

Cheng, X. and Klaassen, C.D.:  Critical role of PPAR{alpha} in perfluorooctanoic acid- and perfluorodecanoic acid-induced down-regulation of Oatp uptake transporters in mouse livers.  Toxicol. Sci. 106: 37-45, 2008.  PMID: 18703564

Knight, T.R., Choudhuri, S. and Klaassen, C.D.:  Induction of hepatic glutathione S-transferases in male mice by prototypes of various classes of microsomal enzyme inducers.  Toxicol. Sci. 106: 329-338, 2008.  PMID: 18723825

Maher, J.M., Aleksunes, L.M., Dieter, M.Z., Tanaka, Y., Peters, J.M., Manautou, J.E., and Klaassen, C.D.:  Nrf2 and PPAR{alpha}-mediated regulation of hepatic Mrp transporters after exposure to perfluorooctanoic acid and perfluorodecanoic acid.  Toxicol. Sci. 106: 319-328, 2008.  PMID: 18757529

Alnouti, Y., Csanaky, I.L., and Klaassen, C.D.:  Quantitative-profiling of bile acids and their conjugates in mouse liver, bile, plasma, and urine using LC–MS/MS. J. Chromatogr. 873: 209-217, 2008.  PMID: 18801708

Zhang, Y-K, J, Yeager, R.L., and Klaassen, C.D.:  Circadian expression profiles of drug processing genes and transcription factors in mouse liver.  Drug Metab. Dispos. 37: 106-117, 2009.  PMID: 18838502

Cui, Y.J., Cheng, X., Miao-Weaver, Y., and Klaassen, C.D.:  Tissue distribution, gender-divergent expression, ontogeny, and chemical induction of multidrug resistance transporter genes (Mdr1a, Mdr1b, Mdr2) in mice.  Drug Metab. Dispos. 37: 203-210, 2009.  PMID: 18854377

Reisman, S.A., Yeager, R.L., Yamamoto, M., and Klaassen, C.D.:  Increased Nrf2 activation in livers from Keap-1-knockdown mice increases expression of cytoprotective genes that detoxify electrophiles more than those that detoxify reactive oxygen species.  Toxicol. Sci. 108: 35-47, 2009.  PMID: 19129213

Buckley, D.B. and Klaassen, C.D.:  Mechanism of gender-divergent UDP-glucuronosyltransferase mRNA expression in mouse liver and kidney.  Drug Metab. Dispos.  37: 834-840, 2009. PMID: 19131521

Buckley, D.B. and Klaassen, C.D.:  Induction of mouse UDP-glucuronosyltransferase mRNA expression in liver and intestine by activators of AhR, CAR, PXR, PPAR(alpha), and Nrf2.  Drug Metab. Dis. 37: 847-856, 2009.  PMID: 19144771

Reisman, S.A., Csanaky, I.L., Aleksunes, L.M., and Klaassen, C.D.:  Altered disposition of acetaminophen in Nrf2-null and Keap1-knockdown mice.  Toxicol. Sci. 109: 31-40, 2009.  PMID: 19246624

Reisman, S.A., Buckley, D.B., Tanaka, Y., and Klaassen, C.D.:  CDDO-Im protects from acetaminophen hepatotoxicity through induction of Nrf2-dependent genes.  Toxicol. Appl. Pharmacol.  236: 109-114, 2009.  PMID: 19371629

Contact Information

Curtis D. Klaassen
University Distinguished Professor
Department of Internal Medicine
The University of Kansas Medical Center
1000 Hixon; MS1063
3901 Rainbow Boulevard
Kansas City, KS 66160
Phone: (913) 588-7714
Fax: (913) 588-3995
E-mail: cklaasse@kumc.edu

Updated 2/4/12