Multifunctional trophic factors produce distinct, cell-type specific effects and also facilitate cross-talk between nerve cells, blood vessels, and astrocytes. The cell signaling studies are designed to shed light on the cell-specific signal transduction pathways activated by non-erythropoietic derivatives such as carbamylated enrythropoietin. These studies focus on the activation of receptors, key intracellular adaptors, and kinases. A variety of tools and analyses are used, including mass spectrometry-based posttranslational modifications, western blots, immunohistochemistry and immunoprecipitation. Receptor expression levels are manipulated by CRISOR-Cas and RNAi mediated gene knockout and knockdown approaches.