The long-term objectives of this application are to utilize expression profiling of nuclear receptors and theirassociated co-regulators and target genes to answer fundamental questions about various physiologic andpathophysiologic processes, including diseases associated with metabolic syndrome, cancer, and aging. Ourhypothesis is that NRs represent a principle component set of expressed genes that have the predictivepower to provide diagnostic, prognostic, and therapeutic information on an individual basis. An equallyimportant goal of this work is to provide a web-based database that contains this expression profilinginformation as a mineable resource to the scientific community. Following on the success of the previousfunding period to establish a high-throughput, quantitative real-time PCR method for assaying nuclearreceptor expression, we plan the following three specific aims: 1) NR expression profiling from human patientsamples with various metabolic diseases and cancer. We will use QPCR to measure nuclear receptor (NR)and coregulator (CoR) mRNA expression in samples from patients with non-alcoholic steatosis hepatitis(NASH), and lung and breast cancers. 2) NR expression profiling in mouse models of metabolic diseasesand aging. We plan to use both dietary and genetic approaches to assess the dynamics of NR and CoRmRNA expression in tissues collected from wild-type and ob/ob mice treated with NR ligands, as well as inwild-type mice over the course of aging. 3) Expression profiling of additional gene families that correlate toNR expression. We will apply the same standardized QPCR profiling assays to measure the ATP-bindingcassette transporters (ABCs), cytochrome p450s (p450s), and microRNAs (miRNAs). Previous data haveshown these gene families are either effectors and/or primary targets of NR action. Samples harvestedduring the previous funding period and those acquired as part of Aims 1 and 2 will be interrogated. Togetherwith other components of the NURSA consortium, these aims should provide an invaluable resource to theNR field, and establish new translational methods for diagnosing and treating human disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program--Cooperative Agreements (U19)
Project #
2U19DK062434-06
Application #
7350607
Study Section
Special Emphasis Panel (ZDK1-GRB-9 (M1))
Project Start
2007-08-01
Project End
2012-07-31
Budget Start
2007-08-01
Budget End
2008-07-31
Support Year
6
Fiscal Year
2007
Total Cost
$391,247
Indirect Cost
Name
Baylor College of Medicine
Department
Type
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
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