Our research focuses on signaling pathways triggered by inositol phospholipid PtdIns(3,4,5)P3, which has been implicated in various cellular processes such as proliferation, growth, apoptosis, polarity, chemotaxis and cytoskeletal rearrangement. PtdIns(3,4,5)P3 exerts its function by mediating protein translocation via binding to their pleckstrin homolog (PH)-domains. Membrane translocation of PH-domains was previously thought to be dependent solely upon concentrations of PtdIns(3,4,5)P3 in the membrane which is regulated by PI3K and PTEN. Recently, we discovered that two intracellular inositol phosphates InsP7 and Ins(1,3,4,5)P4 compete with PtdIns(3,4,5)P3 for binding to the PH domains, and thereby attenuate their membrane translocation. This result provides another level of regulation for PH domain translocation, namely relative levels of InsP7 and PtdIns(3,4,5)P3. Our lab will continue to elucidate the molecular mechanism and the physiological consequence of the inositol phosphate-mediated suppression of PtdIns(3,4,5)P3 signaling in a variety of cellular processes. #p Our lab is also interested in the role of neutrophils and innate immunity in hematopoiesis and leukemogenesis. Neutrophils in the bone marrow and circulation release various factors that can modulate hematopoiesis and myelopoiesis. We are currently exploring the role of ROS and proteases in infection-induced myelopoiesis. We are also interested in the molecular and cellular mechanisms that govern the release (mobilization) of neutrophils from the bone marrow during the course of inflammation. Similar mechanisms may also be involved in mobilization of leukemia cells.