Email

moore@bcm.edu

Positions

Professor

Mol & Cell Biology-Dmoore
Baylor College of Medicine
Houston, TX US

Professor

Program in Integrative Molecular and Biomedical Sciences
Baylor College of Medicine

Professor

Program in Developmental Biology
Baylor College of Medicine

Professor

Molecular and Human Genetics
Baylor College of Medicine

Professor

USDA/ARS Children's Nutrition Research Center
Baylor College of Medicine

Faculty Senator

Baylor College of Medicine
Houston, Texas United States

The R. P. Doherty, Jr. Welch Chair in Science

Baylor College of Medicine
Houston, Texas United States

Member

Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
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 Cancer
The 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’s 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 "Research Resource: The Estrogen Receptor a Cistrome Defined by DamIP.." Mol. Endocrinol.. 2012 Feb;26(2):349-57. Pubmed PMID: 22207717
• Lee JM, Lee YK, Mamrosh JL, Busby SA, Griffin PR, Pathak MC, Ortlund EA, Moore DD "A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects.." Nature. 2011 Jun 23;474(7352):506-10. Pubmed PMID: 21614002
• Dong B, Saha PK, Huang W, Chen W, Abu-Elheiga LA, Wakil SJ, Stevens RD, Ilkayeva O, Newgard CB, Chan L, Moore DD "Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease.." Proc. Natl. Acad. Sci. U.S.A.. 2009 Nov 3;106(44):18831-6. Pubmed PMID: 19850873
• Ma K, Xiao R, Tseng HT, Shan L, Fu L, Moore DD "Circadian dysregulation disrupts bile acid homeostasis.." PLoS ONE. 2009;4(8):e6843. Pubmed PMID: 19718444