The nuclear receptor family is made up of ligand-activated transcriptional regulators that have beenimplicated as key regulators of development and metabolic homostatsis of the human body. Many commondiseases such as atherosclerosis, hepatic and pulmonary fibrosis, cancer and chronic inflammation havetheir origins in loss metabolic or developmental control. We will focus on exploring the mRNA expressionprofile of nuclear hormone receptors in human diseases including but not limited to nonalcoholicsteatohepatitis (NASH), atherosclerosis and diabetes, skin diseases (eg psoriasis), brain tumors and myeloidleukemia. In addition, selective mouse models will be used to examine the expression pattern of mRNA NRfamily during early and late phases of progression of metabolic and inflammation diseases such asatherosclerosis. Profiling will be achieved through the quantitative PCR NR NURSA platform which providesa sensitive and highly quantitative method for analyzing NR mRNA levels. The data collected from thesestudies will be contained within a shared Bioinformatics Resource for data mining by the wider scientificcommunity. In addition one of the major goals of this project is to develop of new analytical tools fordetermining and altering the expression of all members of the nuclear receptor family in specific cells andtissues. In addition, we will design, develop and validate a comprehensive lentiviral shRNA knockdownlibrary that targets the entire NR family. Finally, we will use the library to interrogate cell lines and animalmodels of metabolic, inflammatory and cancer states in which a receptor has been shown to have a dynamicand/or dominant expression profile. The NR lentiviral shRNA knockdown library will be made available otherNURSA members with the eventual goal of supplying the research community with a powerful new tools foranalyzing NR function.
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