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Melissa Runge-Morris, M.D. |
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Wayne State University |
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Tel. |
(313) 964-1521 |
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Fax. |
(313) 577-6739 |
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Email: |
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Address: |
Institute of Environmental Health Sciences
Wayne State University |
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| Research Interests: | ||
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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. |
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| Select Publications: | ||
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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. PMID: 15635043 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. 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. |
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