Positions
- Professor
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Mol & Cell Biology-Dmoore
草榴社区入口
Houston, TX US
- Professor
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Program in Integrative Molecular and Biomedical Sciences
草榴社区入口
- Professor
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Program in Developmental Biology
草榴社区入口
- Professor
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Molecular and Human Genetics
草榴社区入口
- Professor
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USDA/ARS Children's Nutrition Research Center
草榴社区入口
- Faculty Senator
-
草榴社区入口
Houston, Texas United States
- The R. P. Doherty, Jr. Welch Chair in Science
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草榴社区入口
Houston, Texas United States
- Member
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Dan L Duncan Comprehensive Cancer Center
草榴社区入口
Houston, Texas United States
Education
- AB from Brown University
- 01/1974 - Providence, Rhode Island United States
- PhD from University Of Wisconsin, Madison
- 01/1979 - Madison, Wisconsin United States
Professional Interests
- Functions of members of the nuclear hormone receptor superfamily
Professional Statement
Nuclear Hormone Receptors Regulate Metabolism and CancerThe 48 members of the nuclear hormone receptor superfamily function as ligand-dependent or, in some cases, ligand-independent transcription factors. The major goal of this laboratory is to understand the roles of the newer members of this superfamily, particularly their impact on metabolic and oncogenic pathways in the liver.
One major focus is on CAR, which functions to regulate the response of the liver to xenobiotics, potentially toxic foreign compounds. Activation of CAR by specific xenobiotic stimuli, and also by toxic endogenous compounds such as bile acids and bilirubin, increases the liver鈥檚 ability to metabolize and eliminate them. CAR-dependent responses are generally protective, but can be deleterious. Thus, chronic activation of CAR by non-genotoxic carcinogens results in liver tumors, due to direct effects of CAR on both hepatocyte proliferation and apoptosis. We are pursuing both the mechanism of this tumor promotion and therapeutic approaches that block it.
FXR is the primary nuclear receptor for bile acids, cholesterol metabolites that are important regulators of lipid homeostasis. FXR regulates a number of key metabolic target genes including SHP, an unusual orphan receptor that lacks a DNA binding domain. SHP represses transactivation by several other nuclear receptors and decreases expression of target genes, including the rate limiting enzyme for bile acid production. Bile acids can promote liver growth, and we have found that FXR activation is essential for normal liver regeneration. Bile acids can also act as tumor promoters, and we are studying the role of the Hippo growth control pathway as the basis for spontaneous tumorigenesis in double knockout mice lacking both FXR and SHP. We will continue to use pharmacologic and mouse knockout approaches to explore the diverse metabolic regulatory functions of the nuclear hormone receptors.
Websites
Selected Publications
- Xiao R, Sun D, Ayers S, Xi Y, Li W, Baxter JD, Moore DD "." Mol. Endocrinol.. 2012 Feb;26(2):349-57. Pubmed PMID:
- Lee JM, Lee YK, Mamrosh JL, Busby SA, Griffin PR, Pathak MC, Ortlund EA, Moore DD "." Nature. 2011 Jun 23;474(7352):506-10. Pubmed PMID:
- Dong B, Saha PK, Huang W, Chen W, Abu-Elheiga LA, Wakil SJ, Stevens RD, Ilkayeva O, Newgard CB, Chan L, Moore DD "." Proc. Natl. Acad. Sci. U.S.A.. 2009 Nov 3;106(44):18831-6. Pubmed PMID:
- Ma K, Xiao R, Tseng HT, Shan L, Fu L, Moore DD "." PLoS ONE. 2009;4(8):e6843. Pubmed PMID:
- Dong B, Qatanani M, Moore DD "." Hepatology. 2009 Aug;50(2):622-9. Pubmed PMID:
- Huang W, Ma K, Zhang J, Qatanani M, Cuvillier J, Liu J, Dong B, Huang X, Moore DD "." Science. 2006 Apr 14;312(5771):233-6. Pubmed PMID:
- Ma K, Saha PK, Chan L, Moore DD "." J. Clin. Invest.. 2006 Apr;116(4):1102-9. Pubmed PMID:
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