Nathan J Cherrington, PhD
Associate Professor
Department:
Pharmacology and Toxicology
(520) 626-0219
Secondary Phone:
(520) 626-2823
Fax:
(520) 626-4063
E-mail:
Location:
Pharmacy 000412
Bio / Research:
Current research interests include studying molecular mechanisms of liver toxicity and employing a functional genomics approach based on flexible small-scale arrays to measure the expression of xenobiotic transporter and drug metabolism genes.
Specifically, thousands of people suffer from liver diseases such as biliary cirrhosis, steatosis, hepatitis or what is commonly referred to as chronic liver failure. During the early stages of these diseases, the normal functions of the liver slow down. Normally, the liver metabolizes toxic compounds and excretes them into the feces. However, in diseased patients, these toxic compounds can’t be eliminated fast enough and begin to accumulate in the liver and cause considerable toxicity. This in turn compounds the original condition leading to a progression of the disease and eventually liver failure.
Hepatic transporters are the driving force behind the excretion of these toxic substances and when turned off, cause the accumulation and toxicity associated with liver disease. However, a separate small group of transporters may be used to move toxic compounds from the liver, back into the blood (to be excreted in urine), thereby decreasing the exposure and toxicity to the liver. If the precise mechanism for the regulation of these transporters can be determined, new drug therapies that could artificially increase the capacity of diseased livers to excrete toxic substances and reduce liver failure would be possible. For this reason, pharmacologic intervention by targeting these new molecular pathways to relieve toxicity may prove to be vitally important to the long-term health of thousands of patients.
Education:BS, Brigham Young University, 1993, Zoology
PhD, North Carolina State University, 1997, Toxicology
PD, University of Kansas Medical Center, 1998-2002, Toxicology
Maher JM, Slitt AL, Cherrington NJ, Cheng X, Klaassen CD. Tissue Distribution and Hepatic and Renal Ontogeny of the Multidrug Resistance=Associated Protein (MRP) Family in Mice. Drug Metab Dispos 2005 33(7):947-55
Erickson RP, Bhattacharyya A, Hunter RJ, Heidenreich RA, Cherrington NJ. Liver Disease with Altered Bile Acid Transport in Niemann-Pick C Mice on a High Fat, 1% Cholesterol Diet. Am J Physiol Gastrointest Liver Physiol. 2005 In Press
Rose RL, Tang J, Choi J, Cao Y, Usmani A, Cherrington N, Hodgson E. Pesticide metabolism in humans, including polymorphisms. Scand J Work Environ Health 2005;31 suppl 1:156-163
Augustine, L.M., Markelewicz, R.J., Boekelheide, K., and Cherrington, N.J. Xenobiotic and endobiotic transporter mRNA expression in the blood-testis barrier. Drug Metab. Dispos. 2005 33:182-9
Aleksunes, L.M., Slitt, A.L., Cherrington, N.J., Thibodeau, M.S., Klaassen, C.D., and Manautou, J.E. Differential expression of mouse hepatic transporter genes in response to acetaminophen and carbon tetrachloride. Tox Sci 2005 83: 44-52
Li, N., Choudhuri, S., Cherrington, N.J., and Klaassen, C.D. Down-regulation of mouse organic anion transporting polypeptide 4 (Oatp4; Slc21a10) by lipopolysaccharide is through the toll-like receptor 4 (TLR4). Drug Metab Dispos 2004 32: 1265-1271.
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 2004 32: 734-741
Wright, S.H., Evans, K.K., Zhang, X., Cherrington, N.J., Sitar, D.S., and Dantzler, W.H. Functional map of TEA transport activity in isolated rabbit renal proximal tubules. Am J Physiol Renal Physiol. 2004 287(3):F442-51
Cherrington, N.J., Slitt, A.L., Maher, J.M., Zhang, X.X., Zhang, J., Huang, W.,
Wan, 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. 2003; 31:1315-9.
Choudhuri*, S., Cherrington*, N.J., Li, N. and Klaassen, C.D. (* denotes equal contribution) Constitutive Expression of various xenobiotic and endobiotic transporter mRNA in the choroid plexus of adult sprague-dawley rats. Drug Metab Dispos. 2003; 31:1337-45.
Slitt, A.L. Cherrington, N.J. Maher, J.M. and Klaassen, C.D. Increased plasma levels of acetaminophen-glucuronide is associated with induction of multidrug resistance protein 3 (Mrp3) in liver. Drug Metab Dispos. 2003; 31(9):1176-86..
Shelby, M.K., Cherrington, N.J., Vansell, N.R., and Klaassen, C.D. Tissue expression of the rat UDP-Glucuronosyltransferase superfamily. Drug Metab Dispos. 2003 Mar;31(3):326-33.
Buist, S.C.N., Cherrington, N.J., and Klaassen, C.D. Endocrine control of rat organic anion transporter expression. Drug Metab Dispos. 2003 31(5):559-64.
Brady, J.M., Cherrington, N.J., Hartley, D.P., Li, N. and Klaassen, C.D. Tissue expression and chemical inducibility of multiple drug resistance genes in rats. Drug Metab Dispos. 2002 30(7):838-44
Park, J.D., Cherrington, N.J., and Klaassen, C.D. Intestinal absorption of cadmium is regulated by divalent metal transporter 1 in rats. Toxicol Sci. 2002; 68(2):288-94
Li, N., Hartley, D.P., Cherrington, N.J. and Klaassen, C.D. Tissue expression, ontogeny, and inducibility of organic anion transporting polypeptide 4 (Oatp4). J Pharmacol Exp Ther 2002; 301 (2): 551-60.
Buist, S.C.N., Cherrington, N.J., Choudhuri, S., Hartley, D.P. and Klaassen, C.D. Tissue and developmental expression of rat organic anion transporters (OATs). J Pharmacol Exp Ther 2002; 301(1): 145-51.
Slitt, A.L., Cherrington, N.J., Hartley, D.P., Leazer, T.M. and Klaassen, C.D. Tissue specific expression of the organic cation transporters. Drug Metab Dispos 2002; 30: 212-219.
Cherrington, N.J. Hartley, D.P. Li, N. Johnson, D.R. and Klaassen, C.D. Organ distribution of multidrug resistance proteins 1, 2, and 3 (Mrp1, 2 and 3) mRNA and hepatic induction by constitutive androstane receptor (CAR) activators in rat. J Pharmacol Exp Ther 2002; 300(1): 97-104.