Institute of Environmental Health Sciences
(313) 577-5598 (Phone)
(313) 577-6739 (Fax)
Dr. Runge-Morris' primary research program is dedicated to understanding the molecular mechanisms that regulate the expression of the sulfotransferase multigene family. The cytosolic sulfotransferase conjugating enzymes are vitally important to drug metabolism. These enzymes detoxify many xenobiotic and endogenous substrates by forming more polar products that are amenable to excretion and elimination from the body. However, if the sulfated conjugate is unstable, loss of the labile sulfate group can create highly reactive electrophiles that may damage cellular macromolecules such as DNA. Many of the sulfotransferases in liver and other tissues, have been implicated in the bioactivation of environmental carcinogens. In addition to these important biological functions, the sulfotransferases also modulate intra-tissue hormone activity. Because sulfated hormones generally are receptor inactive, induction of sulfotransferase gene expression can reduce the levels of bioactive steroid hormone that are available to bind to cellular receptors. In human pathology, the sulfotransferases are in a prime position to influence the development and progression of hormone responsive tumors such as breast and prostate cancer.
Dr. Runge-Morris' laboratory is currently investigating the key transcription factor and cis-acting response elements that are responsible for regulating changes in sulfotransferase gene transcription. Recently, her research group reported that glucocorticoid hormones and xenobiotics such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and phenobarbital produce differential effects on the mRNA expression of individual sulfotransferase isoforms in rat liver and in primary cultured rat hepatocytes. As an overall research objective, Dr. Runge-Morris maintains that identifying and characterizing the factors that control gene expression during critical periods of development and aging will lead to new insights on disease mechanisms in humans.
Fang HL, Strom SC, Cai H, Falany CN, Kocarek TA, Runge-Morris M. Regulation of human hepatic hydroxysteroid sulfotransferase gene expression by the peroxisome proliferator-activated receptor alpha transcription factor. Mol Pharmacol. 2005 Apr;67(4):1257-67. Epub 2005 Jan 5.
Fang HL, Abdolalipour M, Duanmu Z, Smigelski JR, Weckle A, Kocarek TA, Runge-Morris M. Regulation of glucocorticoid-inducible hydroxysteroid sulfotransferase (SULT2A-40/41) gene transcription in primary cultured rat hepatocytes: role of CCAAT/enhancer-binding protein liver-enriched transcription factors. Drug Metab Dispos. 2005 Jan;33(1):147-56. Epub 2004 Oct 22.
Shenoy SD, Spencer TA, Mercer-Haines NA, Abdolalipour M, Wurster WL, Runge-Morris M, Kocarek TA. Induction of CYP3A by 2,3-oxidosqualene:lanosterol cyclase inhibitors is mediated by an endogenous squalene metabolite in primary cultured rat hepatocytes. Mol Pharmacol. 2004 May;65(5):1302-12. PMID: 15102959
Shenoy SD, Spencer TA, Mercer-Haines NA, Alipour M, Gargano MD, Runge-Morris M, Kocarek TA. CYP3A induction by liver x receptor ligands in primary cultured rat and mouse hepatocytes is mediated by the pregnane X receptor. Drug Metab Dispos. 2004 Jan;32(1):66-71.
Kocarek TA, Shenoy SD, Mercer-Haines NA, Runge-Morris M. Use of dominant negative nuclear receptors to study xenobiotic-inducible gene expression in primary cultured hepatocytes.
J Pharmacol Toxicol Methods. 2002 May-Jun;47(3):177-87. PMID: 12628309
Duanmu Z, Kocarek TA, Runge-Morris M. Transcriptional regulation of rat hepatic aryl sulfotransferase (SULT1A1) gene expression by glucocorticoids. Drug Metab Dispos. 2001 Aug;29(8):1130-5. PMID: 11454732
Wu W, Kocarek TA, Runge-Morris M. Sex-dependent regulation by dexamethasone of murine hydroxysteroid sulfotransferase gene expression. Toxicol Lett. 2001 Mar 8;119(3):235-46.
Runge-Morris M, Wu W, Kocarek TA. Regulation of rat hepatic hydroxysteroid sulfotransferase (SULT2-40/41) gene expression by glucocorticoids: evidence for a dual mechanism of transcriptional control. Mol Pharmacol. 1999 Dec;56(6):1198-206. PMID: 10570047
Runge-Morris M. Regulation of sulfotransferase gene expression by glucocorticoid hormones and xenobiotics in primary rat hepatocyte culture. Chem Biol Interact. 1998 Feb 20;109(1-3):315-27. PMID: 9566755
Runge-Morris M, Rose K, Kocarek TA. Regulation of rat hepatic sulfotransferase gene expression by glucocorticoid hormones. Drug Metab Dispos. 1996 Oct;24(10):1095-101.