Melissa Runge-Morris, Ph.D. M.D.

Melissa Runge-Morris, Ph.D. M.D.

Director

m.runge-morris@wayne.edu

(313) 577-6739 (fax)

Melissa Runge-Morris, Ph.D. M.D.

Address

Institute of Environmental Health Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201

Office Phone

(313) 577-5598

Research Interests

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.

Department

Institute of Environmental Health Sciences

Selected Publications


Dubaisi S, Barrett KG, Fang H, Guzman-Lepe J, Soto-Gutierrez A, Kocarek TA, Runge-Morris M. Regulation of Cytosolic Sulfotransferases in Models of Human Hepatocyte Development. Drug Metab Dispos. 2018 Aug;46(8):1146-1156. doi: 10.1124/dmd.118.081398. Epub 2018 Jun 1. PubMed PMID: 29858374; PubMed Central PMCID: PMC6038032.

Guidry AL, Tibbs ZE, Runge-Morris M, Falany CN. Expression, purification and characterization of human cytosolic sulfotransferase (SULT) 1C4. Horm Mol Biol Clin Investig. 2017 Jan 1;29(1):27-36. doi: 10.1515/hmbci-2016-0053. PubMed PMID: 28222028; PubMed Central PMCID: PMC5608031.

Dubaisi S, Fang H, Kocarek TA, Runge-Morris M. Transcriptional Regulation of Human Cytosolic Sulfotransferase 1C3 by Peroxisome Proliferator-Activated Receptor γ in LS180 Human Colorectal Adenocarcinoma Cells. Mol Pharmacol. 2016 Nov;90(5):562-569. Epub 2016 Aug 26. PubMed PMID: 27565680; PubMed Central PMCID: PMC5074451.

Barrett KG, Fang H, Kocarek TA, Runge-Morris M. Transcriptional Regulation of Cytosolic Sulfotransferase 1C2 by Vitamin D Receptor in LS180 Human Colorectal Adenocarcinoma Cells. Drug Metab Dispos. 2016 Aug;44(8):1431-4. doi: 10.1124/dmd.116.070300. Epub 2016 Apr 29. PubMed PMID: 27130351; PubMed Central PMCID: PMC4986619.

Barrett KG, Fang H, Cukovic D, Dombkowski AA, Kocarek TA, Runge-Morris M. Upregulation of UGT2B4 Expression by 3'-Phosphoadenosine-5'-Phosphosulfate Synthase Knockdown: Implications for Coordinated Control of Bile Acid Conjugation. Drug Metab Dispos. 2015 Jul;43(7):1061-70. doi: 10.1124/dmd.114.061440. Epub 2015 May 6. PubMed PMID: 25948711; PubMed Central PMCID: PMC4468435.

Rondini EA, Fang H, Runge-Morris M, Kocarek TA. Regulation of human cytosolic sulfotransferases 1C2 and 1C3 by nuclear signaling pathways in LS180 colorectal adenocarcinoma cells. Drug Metab Dispos. 2014 Mar;42(3):361-8. doi: 10.1124/dmd.113.055673. Epub 2013 Dec 11. PubMed PMID: 24335393; PubMed Central PMCID: PMC3935136.

Duniec-Dmuchowski Z, Rondini EA, Tibbs ZE, Falany CN, Runge-Morris M, Kocarek TA. Expression of the orphan cytosolic sulfotransferase SULT1C3 in human intestine: characterization of the transcript variant and implications for function. Drug Metab Dispos. 2014 Mar;42(3):352-60. doi: 10.1124/dmd.113.055665. Epub 2013 Dec 11. Erratum in: Drug Metab Dispos. 2014 May;42(5):853. PubMed PMID: 24335392; PubMed Central PMCID: PMC3935139.

Runge-Morris M, Falany C. Emerging insights into the function and regulation of the cytosolic sulfotransferases. Preface. Drug Metab Rev. 2013 Nov;45(4):387. doi: 10.3109/03602532.2013.842375. Epub 2013 Sep 27. PubMed PMID: 24074060.

Runge-Morris M, Kocarek TA. Expression of the sulfotransferase 1C family: implications for xenobiotic toxicity. Drug Metab Rev. 2013 Nov;45(4):450-9. doi: 10.3109/03602532.2013.835634. Epub 2013 Sep 12. Review. PubMed PMID: 24028175.

Barrett KG, Fang H, Gargano MD, Markovich D, Kocarek TA, Runge-Morris M. Regulation of murine hepatic hydroxysteroid sulfotransferase expression in hyposulfatemic mice and in a cell model of 3'-phosphoadenosine-5'-phosphosulfate deficiency. Drug Metab Dispos. 2013 Aug;41(8):1505-13. doi: 10.1124/dmd.113.051912. Epub 2013 May 14. PubMed PMID: 23674610; PubMed Central PMCID: PMC3716305.

Runge-Morris M, Kocarek TA, Falany CN. Regulation of the cytosolic sulfotransferases by nuclear receptors. Drug Metab Rev. 2013 Feb;45(1):15-33. doi: 10.3109/03602532.2012.748794. Review. PubMed PMID: 23330539; PubMed Central PMCID: PMC3831883.

Salman ED, He D, Runge-Morris M, Kocarek TA, Falany CN. Site-directed mutagenesis of human cytosolic sulfotransferase (SULT) 2B1b to phospho-mimetic Ser348Asp results in an isoform with increased catalytic activity. J Steroid Biochem Mol Biol. 2011 Nov;127(3-5):315-23. doi: 10.1016/j.jsbmb.2011.07.010. Epub 2011 Aug 6. PubMed PMID: 21855633; PubMed Central PMCID: PMC3220804.

Fu J, Fang H, Paulsen M, Ljungman M, Kocarek TA, Runge-Morris M. Regulation of estrogen sulfotransferase expression by confluence of MCF10A breast epithelial cells: role of the aryl hydrocarbon receptor. J Pharmacol Exp Ther. 2011 Nov;339(2):597-606. doi: 10.1124/jpet.111.185173. Epub 2011 Aug 9. PubMed PMID: 21828262; PubMed Central PMCID: PMC3199978.

Bai Q, Xu L, Kakiyama G, Runge-Morris MA, Hylemon PB, Yin L, Pandak WM, Ren S. Sulfation of 25-hydroxycholesterol by SULT2B1b decreases cellular lipids via the LXR/SREBP-1c signaling pathway in human aortic endothelial cells. Atherosclerosis. 2011 Feb;214(2):350-6. doi: 10.1016/j.atherosclerosis.2010.11.021. Epub 2010 Nov 26. PubMed PMID: 21146170; PubMed Central PMCID: PMC3031658.

Runge-Morris M, Kocarek TA. Regulation of sulfotransferase and UDP-glucuronosyltransferase gene expression by the PPARs. PPAR Res.
2009;2009:728941. doi: 10.1155/2009/728941. Epub 2009 Aug 10. PubMed PMID: 19680455; PubMed Central PMCID: PMC2724710.

Cook IT, Duniec-Dmuchowski Z, Kocarek TA, Runge-Morris M, Falany CN. 24-hydroxycholesterol sulfation by human cytosolic sulfotransferases: formation of monosulfates and disulfates, molecular modeling, sulfatase sensitivity, and inhibition of liver x receptor activation. Drug Metab Dispos. 2009 Oct;37(10):2069-78. doi: 10.1124/dmd.108.025759. Epub 2009 Jul 9. PubMed PMID: 19589875; PubMed Central PMCID: PMC2769038.

Falany CN, He D, Li L, Falany JL, Wilborn TW, Kocarek TA, Runge-Morris M. Regulation of hepatic sulfotransferase (SULT) 1E1 expression and effects on estrogenic activity in cystic fibrosis (CF). J Steroid Biochem Mol Biol. 2009 Mar;114(1-2):113-9. doi: 10.1016/j.jsbmb.2009.02.009. Epub 2009 Mar 3. PubMed PMID: 19429440; PubMed Central PMCID: PMC3855421.

Fu J, Weise AM, Falany JL, Falany CN, Thibodeau BJ, Miller FR, Kocarek TA, Runge-Morris M. Expression of estrogenicity genes in a lineage cell culture model of human breast cancer progression. Breast Cancer Res Treat. 2010 Feb;120(1):35-45. doi: 10.1007/s10549-009-0363-8. Epub 2009 Mar 24. PubMed PMID: 19308726; PubMed Central PMCID: PMC3772670.

Duniec-Dmuchowski Z, Fang HL, Strom SC, Ellis E, Runge-Morris M, Kocarek TA. Human pregnane X receptor activation and CYP3A4/CYP2B6 induction by 2,3-oxidosqualene:lanosterol cyclase inhibition. Drug Metab Dispos. 2009 Apr;37(4):900-8. doi: 10.1124/dmd.108.025130. Epub 2009 Jan 21. PubMed PMID: 19158313; PubMed Central PMCID: PMC2680536.

Kocarek TA, Duanmu Z, Fang HL, Runge-Morris M. Age- and sex-dependent expression of multiple murine hepatic hydroxysteroid sulfotransferase (SULT2A) genes. Biochem Pharmacol. 2008 Oct 15;76(8):1036-46. doi: 10.1016/j.bcp.2008.07.032. Epub 2008 Aug 5. PubMed PMID: 18725207; PubMed Central PMCID: PMC3086055.

Fang HL, Strom SC, Ellis E, Duanmu Z, Fu J, Duniec-Dmuchowski Z, Falany CN, Falany JL, Kocarek TA, Runge-Morris M. Positive and negative regulation of human hepatic hydroxysteroid sulfotransferase (SULT2A1) gene transcription by rifampicin: roles of hepatocyte nuclear factor 4alpha and pregnane X receptor. J Pharmacol Exp Ther. 2007 Nov;323(2):586-98. Epub 2007 Aug 8. PubMed PMID: 17687072.

Thomas RD, Green MR, Wilson C, Weckle AL, Duanmu Z, Kocarek TA, Runge-Morris M. Cytochrome P450 expression and metabolic activation of cooked food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in MCF10A breast epithelial cells. Chem Biol Interact. 2006 Apr 15;160(3):204-16. Epub 2006 Mar 9. PubMed PMID: 16527260.

Duanmu Z, Weckle A, Koukouritaki SB, Hines RN, Falany JL, Falany CN, Kocarek TA, Runge-Morris M. Developmental expression of aryl, estrogen, and hydroxysteroid sulfotransferases in pre- and postnatal human liver. J Pharmacol Exp Ther. 2006 Mar;316(3):1310-7. Epub 2005 Dec 9. PubMed PMID: 16339912.

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.
PMID: 15502011

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.
PMID: 14709622

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.
PMID: 11246177

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.
PMID: 8894510