In the last two funding cycles, the investigators of this Program Project Grant (PPG) have largely relied on genetically manipulated mice (GMM) to study the physiological and pathological roles of genes in the steroid receptor coactivator (SRC) family and the nuclear receptor COUP-TFII in organ function and metabolism. The high quality of mouse services provided by Core A has played an essential role in the great success of this PPG. In the next funding cycle, all projects of this PPG will continue to be heavily dependent on the usage of GMM. More than 18 mouse lines will be used and thousands of GMM will be needed for the proposed studies of this PPG. Therefore, the role of Core A remains essential for the continued success of this PPG. Core A is dedicated to this PPG by achieving 3 major objectives. 1) Core A will use its specialized and state-of-the-art expertise, equipment and facilities to provide essential high quality mouse services to support all projects of this PPG. Core A has a high quality mouse service team with adequate expertise, equipment and facilities for generation of new transgenic/knockout mouse lines, for breeding and maintenance of all existing mouse lines and for performance of mouse genotype analysis. Core A will provide age, sex and genotype-matched mice to individual investigators of this PPG for their experiments. 2) Core A will provide assistance to all projects of this PPG for mouse phenotypic characterization. Core A will use its expertise to assist investigators of this PPG to characterize mouse metabolic phenotypes. Specifically, Core A can help investigators to perform animal surgeries, organ dissections, tail vein injection, special diet feeding, analysis of circadian physiology-regulated metabolism. Clams assays, etc. 3) Core A will integrate efficient usage of animal resources by all projects of this PPG. Core A will minimize the total cost of animal experiments in this PPG by consolidating the usage of equipment, expertise and animal resources. Core A will also ensure the efficient usage of animal resources with appropriate ethical care. In addition, Core A will serve as a resource for execution and training in the use of all animal manipulations needed in this PPG and oversee the human care and use of experimental animals. Core A will minimize the total cost of animal experiments in this PPG by consolidating the usage of equipment, expertise and animal resources. Core A will also ensure the efficient usage of animal resources with appropriate ethical care.
Because many experiments can not be done in human and because many gene functions and pathways regulating energy balance and metabolic rate are similar in human and mouse, genetically manipulated mouse models become essential for this PPG to study the roles and mechanisms of coregulators and nuclear receptors in metabolic diseases. Core A will generate and maintain all mouse models and provide high quality mouse services to guarantee the success of this PPG.
|Dasgupta, Subhamoy; Rajapakshe, Kimal; Zhu, Bokai et al. (2018) Metabolic enzyme PFKFB4 activates transcriptional coactivator SRC-3 to drive breast cancer. Nature 556:249-254|
|Rohira, Aarti D; Yan, Fei; Wang, Lei et al. (2017) Targeting SRC Coactivators Blocks the Tumor-Initiating Capacity of Cancer Stem-like Cells. Cancer Res 77:4293-4304|
|Zhao, Fei; Franco, Heather L; Rodriguez, Karina F et al. (2017) Elimination of the male reproductive tract in the female embryo is promoted by COUP-TFII in mice. Science 357:717-720|
|Xu, Yong; O'Malley, Bert W; Elmquist, Joel K (2017) Brain nuclear receptors and body weight regulation. J Clin Invest 127:1172-1180|
|Xu, Y; Qin, L; Sun, T et al. (2017) Twist1 promotes breast cancer invasion and metastasis by silencing Foxa1 expression. Oncogene 36:1157-1166|
|Xie, Xin; Wu, San-Pin; Tsai, Ming-Jer et al. (2017) The Role of COUP-TFII in Striated Muscle Development and Disease. Curr Top Dev Biol 125:375-403|
|Yi, Ping; Wang, Zhao; Feng, Qin et al. (2017) Structural and Functional Impacts of ER Coactivator Sequential Recruitment. Mol Cell 67:733-743.e4|
|Lee, Hui-Ju; Kao, Chung-Yang; Lin, Shih-Chieh et al. (2017) Dysregulation of nuclear receptor COUP-TFII impairs skeletal muscle development. Sci Rep 7:3136|
|Wang, Leiming; Xu, Mafei; Qin, Jun et al. (2016) MPC1, a key gene in cancer metabolism, is regulated by COUPTFII in human prostate cancer. Oncotarget 7:14673-83|
|Xie, Xin; Tsai, Sophia Y; Tsai, Ming-Jer (2016) COUP-TFII regulates satellite cell function and muscular dystrophy. J Clin Invest 126:3929-3941|
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