Children's National Medical Center Principal Investigator, Children's Research Institute  Center for Cancer and Immunology Research (CCIR)

Dr. Liu's research involves cell signaling between tumor and host normal cells, especially the effect of tumor angiogenesis and immune surprises by tumor derived gangliosides in tumor microenvironment. Most recently published work published in Cancer Research 2006; 66(21) pp. 10408- 10414: “Malignant tumor progression depends upon angiogenesis, requiring vascular endothelial cell migration and proliferation, triggered by tumor-derived vascular endothelial cell growth factor (VEGF).” We show that gangliosides, which are actively shed by tumor cells and bind to normal cells in the tumor microenvironment, have the potential to sensitize vascular endothelial cells to respond to subthreshold levels of VEGF: Ganglioside enrichment of human umbilical vein vascular endothelial cells (HUVEC) caused very low, normally barely stimulatory, VEGF concentrations to trigger robust VEGFR dimerization and autophosphorylation, as well as activation of downstream signaling pathways, and cell proliferation and migration. Thus, by dramatically lowering the threshold for growth factor activation of contiguous normal stromal cells, shed tumor gangliosides may promote tumor progression by causing these normal cells to become increasingly autonomous from growth factor requirements by a process that we term tumor-induced progression of the microenvironment.