Identification of Novel therapeutic targets for inflammatory-associated human disorders

Inflammation is a major hallmark of certain human chronic diseases including type 2 diabetes, obesity, autoimmune diseases and cancer. Detailed investigation of cellular inflammatory pathways help to understand disease process and progression. The Suppressors of Cytokine Signaling (SOCS) proteins act as negative regulators of the main cytokine and growth factor signaling pathways in multiple tissues and as such have important physiological functions. Recent studies demonstrated that inflammatory pathways might be regulated by the cellular actions of SOCS2. In this application we propose to study the molecular mechanism of SOCS2 regulation of inflammatory pathways. Mice will be used to investigate if enhanced GH signaling alter the function of immune cells isolated from wild-type and mice lacking SOCS2 SOCS2 knockout mice (SOCS2-KO). To dissociate the effects of increased growth hormone sensitivity on inflammatory pathways, we will analyze tissue specific knockout of SOCS2 through the use of LoxP-mice and chimera mice obtained from adaptive transfer of bone marrows between the wild-type mice and SOCS2 KO mice. Plasma cytokines, phagocytic activities and gene ex pression will be used to investigate any difference in the function of immune system in all these mice models. We will further try to identify molecular targets of SOCS2 using quantitative proteomic approach. This proposal will present opportunities for future investigations aiming to increase understanding inflammatory processes in chronic human diseases such as type 2 diabetes and obesity. It will also provide a novel therapeutic target for treatment of inflammatory-associated diseases.