Research Interests
Toxicology, biliary drug excretion, metal toxicity, metallothionein, transgenic animals, gene expression
Research in this laboratory is involved in basic regulatory mechanisms in toxicology. Our research has two main aims: (1) to determine the role of cellular membrane transporters in the toxicity of chemicals, (2) and examine how chemicals produce thyroid tumors. In both of these projects we are investigating the role 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 then enhance the elimination of xenobiotics which would be desirable, but might shorten the duration of drugs, which might be undesirable, and enhance the elimination of thyroid hormones, which might be responsible for producing thyroid tumors.
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.
Cherrington, N,J., Slitt, A.L., Maher, J.M., Zhang, X-X., Zhang, J., Huang, W., Wan, Y-J. Y., Moore, D.D., and Klaassen, C.D.: Induction of multidrug resistance protein 3 (Mrp3) in vivo is independent of constitutive androstane receptor. Drug. Metab. Dispos. 31: 1315-1319, 2003.
Choudhuri, S., Cherrington, N.J., Li, N., and Klaassen, C.D.: Constitutive expression of various xenobiotic and endobiotic transporter mRNAs in the choroids plexus of rats. Drug Metab. Dispos. 31: 1337-1345, 2003.
Xie, Y., Liu, J., Liu, Y., Klaassen, C.D., and Waalkes, M.P.: Toxicokinetic and genomic analysis of chronic arsenic exposure in multidrug-resistance mdr1a/1b(-/-) double knockout mice. Mol Cell Biochem. 255: 11-18, 2004.
Chen, C., and Klaassen, C.D.: Rat multidrug resistance protein 4 (Mrp4, Abcc4): molecular cloning, organ distribution, postnatal renal expressing, and chemical inducibility. BBRC 317: 46-53, 2004.
Buist, S.C.N. and Klaassen, C.D.: Rat and mouse differences in gender-predominant expression of organic anion transporter (OAT1-3; SLC22A6-8) mRNA levels. Drug Metab. Dispos 32: 620-625, 2004.
Cherrington, N.J., Slitt, A.L., Li, N., and Klaassen, C.D.: Lipopolysaccharide-mediated regulation of hepatic transporter mRNA levels in rats. Drug Metab. Dispos. 32: 734-741, 2004.
Vansell, N.R., Muppidi, J.R., Habeebu, S.M., and Klaassen, C.D.: Promotion of thyroid tumors in rats by pregnenolone-16α-carbonitrile (PCN) and polychlorinated biphenyl (PCB). Tox. Sci. 81: 50-59, 2004.
Li, N. and Klaassen, C.D.: Role of liver-enriched transcription factors in the down-regulation of organic anion transporting polypeptide 4 (Oatp4; Oatp1b2; Slc21a10) by lipopolysaccharide. Mol Pharmacol 66: 694-701, 2004.
Aleksunes, L.M., Slitt, A.M., Cherrington, N.J., Thibodeau, M.S., Klaassen, D.D., and Manautou, J.E.: Differential expression of mouse hepatic transporter genes in response to acetaminophen and carbon tetrachloride. Tox. Sci 00: 1-8, 2004.
Li, N., Choudhuri, S., Cherrington, N.J., and Klaassen, C.D.: Down-regulation of mouse organic-anion-transporting polypeptide 4 (Oatp4; Oatp1b2; Slc21a10) mRNA by lipopolysaccharide through the toll-like receptor 4 (TLR4).Drug Metab.Dispos. 32: 1265-1271, 2004.
Curtis D. Klaassen
University Distinguished Professor and Chair
Department of Pharmacology, Toxicology and Therapeutics
The University of Kansas Medical Center
MS1018
3901 Rainbow Boulevard
Kansas City, KS 66160
Phone: (913) 588-7500
Fax: (913) 588-7501
E-mail: cklaasse@kumc.edu
Curriculum Vitae in PDF Format
Updated 11/11/2005
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The University of Kansas Medical Center