Sylvester Comprehensive Cancer Center

Zhao-Jun Liu, M.D., Ph.D.

Zhao-Jun Liu, M.D., Ph.D.

Assistant Professor of Surgery

Description of Research

Dr. Liu's research interests span two areas. One of his research interests focuses on signaling pathways and molecular mechanisms involved in tumor initiation, progression, and metastasis. Current research is directed toward elucidation of the Notch signaling pathway and how dysregulation of this pathway leads to melanocytic transformation and melanoma progression. Moreover, Dr. Liu is interested in targeting tumor microenvironment; in particular, stromal fibroblasts and tumor vasculatures, through manipulating Notch signaling. Dr. Liu’s lab has recently identified Notch signaling to be a critical molecular switch in determining biological function of cancer-associated fibroblasts (CAF), and demonstrated that tumor promotive role of CAF can be converted into tumpr suppressor if Notch pathway is activated. The major goal of Dr. Liu's research is to determine if Notch pathway could be a potential therapeutic target for cancer treatment. An additional research interest of Dr. Liu is to investigate the role of Notch signaling in angiogenesis and vascular diseases, including atherosclerosis and aortic aneurysm, as well as the signals and mechanisms underlying endothelial progenitor cell (EPC) homing to target tissues.

Highlights

  • dentified that Notch activity functions as a critical “molecular switch” in determining regulatory effect of tumor stromal fibroblasts on tumor behavior
  • Discovered that cancer-associated fibroblasts (CAF) display low Notch activity
  • Demonstrated that activation of Notch signaling pathway in cancer-associated fibroblasts (CAF) confers CAF a tumor suppressive phenotype
  • Provides a novel approach to target the tumor microenvironment through manipulation of Notch activity in CAF
  • Demonstrated that the Notch1 pathway is activated in human melanoma
  • Demonstrated that Notch signaling is oncogenic in melanoma development and progression
  • Revealed that the oncogenic effects of Notch signaling on melanoma are mediated by activation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)-Akt pathways
  • Highlighted a beta-Catenin-dependent, stage-specific role for Notch1 signaling in promoting the progression of primary melanoma
  • Identified VEGF as an angiogenic factor in controlling Notch and Notch ligand gene expression in endothelial cells
  • Discovered that Notch signaling pathway is activated in luminal endothelial cells at atherosclerotic plaques
  • Discovered that Notch pathway activation results in pro-inflammatory response and senescence of endothelial cells. These findings implicated that dysregulated Notch signaling is involved in atherosclerosis

Selected Cancer-Related Publications

  • Shao H, Huang Q, Liu ZJ. Targeting notch signaling for cancer therapeutic intervention. Adv Pharmacol 65:191-234,2012 Read more »
  • Liu ZJ, Li Y, Tan Y, Xiao M, Zhang J, Radtke F, Velazquez OC. Inhibition of Fibroblast Growth by Notch1 Signaling Is Mediated by Induction of Wnt11-Dependent WISP-1. PLoS One 7:e38811,2012 Read more »
  • Liu ZJ, Tian R, Li Y, An W, Zhuge Y, Livingstone AS, Velazquez OC. Inhibition of Tumor Angiogenesis and Melanoma Growth by Targeting Vascular E-Selectin. Ann Surg 254:450-457,2011 [JIF 7.474] Read more »
  • Shao H, Cai L, Grichnik JM, Livingstone AS, Velazquez OC, Liu ZJ. Activation of Notch1 signaling in stromal fibroblasts inhibits melanoma growth by upregulating WISP-1. Oncogene 30:4316-26,2011 [JIF 7.414] Read more »
  • Goldschmidt-Clermont PJ, Seo DM, Wang L, Beecham GW, Liu ZJ, Vazquez-Padron RI, Dong C, Hare JM, Kapiloff MS, Bishopric NH, Pericak-Vance M, Vance JM, Velazquez OC. Inflammation, stem cells and atherosclerosis genetics. Curr Opin Mol Ther 12:712-23, 2010. Read more »
  • Yin L, Velazquez OC, Liu ZJ. Notch signaling: Emerging molecular targets for cancer therapy. Biochem Pharmacol 80:690-701,2010 Read more »

Programs

Collaborating in the Multidisciplinary Research Program(s):

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