My major interest is determining the role of the BCR/ABL oncogene in the pathogenesis of chronic myelogenous leukemia (CML). I have begun a systematic analysis of identifying the tyrosine phosphorylated targets of BCR/ABL. Through various methodologies, I have helped to identify several key targets of BCR/ABL, including c-CBL, SHP2, CRKL, the inostol 5-phosphatase SHIP, and their interaction with other signaling molecules. I have determined that SHIP is heavily tyrosine phosphorylated in CML cells and the level is reduced. Currently, I am determining the role of SHIP in CML cell signaling and its potential role in the myeloproliferative phenotype. Aside from dissecting the mechanism of SHIP activation in leukemic cells, I have begun to study this molecule's role in normal hematopoietic cells, especially B-cells. Through my interest in CML, I have also defined that ROS play an important role in hematopoiesis. My long term goal is to identify gene targets which can be up- or down-regulated in response to ROS.