A Bioinformatics Approach to Identifying Negative Regulators in the Interleukin-12 Pathway

By gaining a better understanding of how molecular mechanisms of the immune system work and how biological systems respond to different antigenic stimuli, more effective immunotherapies can be designed for the treatment of cancers as well as a variety of for immune-mediated diseases.  Immunotherapies rely on immunomodulators, such as cytokines, to induce or suppress immunologic reactions. Immune responses in cells can be triggered by a cytokine know as Interleukin 12.  Previously, our laboratory has show Interleukin 12 (IL 12) activates STAT 4 and STAT 1 within the JAK-STAT signal transduction pathway. However, expression of these two proteins is differentially regulated. Using microarray data, we will examine gene expression that changes in response to IL-12 and we will identify clusters of genes that are co-regulated. Computational tools will be used to analyze data from the National Center for Biotechnology database for this study. This will help us identify negative feedback regulation and dynamics of the Interleukin 12 signaling pathway.