A significant number of diseases whose effects are felt most acutely in the aging population-atherosclerosis, hypertension, pulmonary fibrosis, and a variety of ocular pathologies-have their roots in the loss of control over metabolic and physiological processes in earlier stages of life. In many cases, orphan nuclear receptors (ONRs) through their participation in the regulation of key tissue-specific target gene networks, are critical components these pathways. This project will focus on the role of ONRs in lipid homeostasis especially as it relates to signal by PPARalpha, gamma, and delta, as well as the steroid xenobiotic receptor SCR and its murine homologue PXR. In order to establish a systematic approach to dissect the functions of these and other orphan nuclear receptors, the PPARs SXR will be studied in a systematic fashion by guidelines developed by the Receptor Atlas Group (RAG). This includes construction of a standardized mouse tissue RNA array for quantitative PCR analysis. In this manner, receptor expression patterns, we well as target genes identified by a universal microarray platform, will be collected to build a relational database of orphan nuclear receptor metabolic function. Additionally, the RAG will utilizes a consistent methodology to analyze the function of orphan nuclear receptors in response to dietary manipulation pharmacologic treatments, and diurnal variations in gene expression in both wild type and transgenic knock-out knock-in mouse lines. The data collected in this manner will be contained within a shared Bioinformatics Resource where RAG and other laboratories can compare nuclear receptor function through a common scientific platform.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19DK062434-01
Application #
6587926
Study Section
Special Emphasis Panel (ZDK1)
Project Start
2002-08-15
Project End
2007-07-31
Budget Start
Budget End
Support Year
1
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
005436803
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Kim, Kang Ho; Choi, Sungwoo; Zhou, Ying et al. (2017) Hepatic FXR/SHP axis modulates systemic glucose and fatty acid homeostasis in aged mice. Hepatology 66:498-509
Fleet, Tiffany; Stashi, Erin; Zhu, Bokai et al. (2016) Genetic and Environmental Models of Circadian Disruption Link SRC-2 Function to Hepatic Pathology. J Biol Rhythms 31:443-60
Wagner, Martin; Choi, Sungwoo; Panzitt, Katrin et al. (2016) Liver receptor homolog-1 is a critical determinant of methyl-pool metabolism. Hepatology 63:95-106
Han, Sang Jun; Begum, Khurshida; Foulds, Charles E et al. (2016) The Dual Estrogen Receptor ? Inhibitory Effects of the Tissue-Selective Estrogen Complex for Endometrial and Breast Safety. Mol Pharmacol 89:14-26
Han, Sang Jun; Jung, Sung Yun; Wu, San-Pin et al. (2015) Estrogen Receptor ? Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis. Cell 163:960-74
Wu, San-Pin; Kao, Chung-Yang; Wang, Leiming et al. (2015) Increased COUP-TFII expression in adult hearts induces mitochondrial dysfunction resulting in heart failure. Nat Commun 6:8245
Tang, Ke; Tsai, Sophia Y; Tsai, Ming-Jer (2015) COUP-TFs and eye development. Biochim Biophys Acta 1849:201-9
Xu, Pingwen; Cao, Xuehong; He, Yanlin et al. (2015) Estrogen receptor-? in medial amygdala neurons regulates body weight. J Clin Invest 125:2861-76
Kang, Yun Kyoung; Putluri, Nagireddy; Maity, Suman et al. (2015) CAPER is vital for energy and redox homeostasis by integrating glucose-induced mitochondrial functions via ERR-?-Gabpa and stress-induced adaptive responses via NF-?B-cMYC. PLoS Genet 11:e1005116
Kida, Yasuyuki S; Kawamura, Teruhisa; Wei, Zong et al. (2015) ERRs Mediate a Metabolic Switch Required for Somatic Cell Reprogramming to Pluripotency. Cell Stem Cell 16:547-55

Showing the most recent 10 out of 214 publications