Education and Training
1981 B.S. Biology, Fudan University, Shanghai, China
1984 M.A. Biochemistry and Biophysics, Columbia University
1985 M.Ph. Biochemistry and Biophysics, Columbia University
1988 Ph.D. Biochemistry and Biophysics, Columbia University
1988-1989 Postdoctoral Fellow (Mentor: Mariano Barbacid, Ph.D.),National Cancer Institute, Frederick, Maryland (The laboratory was relocated to Squibb Medical Research Institute in 1989)
1989-1993 Postdoctoral Fellow (Mentor: Thomas Maciag, Ph.D.), Holland Laboratory, American Red Cross, Rockville, Maryland
1983-1988 Graduate Research Associate, Department of Biochemistry, College of Physicians and Surgeons, Columbia University, New York, NY
1988-1989 Postdoctoral Fellow, Department of Molecular Biology, E.R. Squibb Co. Princeton, NJ
1989-1993 Research Fellow, Department of Molecular Biology, Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, MD
1993-1994 Research Scientist, Research Department, Saint Francis Hospital & Medical Center, Hartford, CT
1994-1999 Scientist I, Department of Experimental Pathology, Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, MD, and Assistant Professor, Department of Anatomy and Cell Biology, University of George Washington, Washington, DC
1999-2001 Scientist II. Department of Experimental Pathology, Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, MD, and Associate Professor, Department of Anatomy and Cell Biology, University of George Washington, Washington, DC
2001-2004 Senior Scientist. Department of Experimental Pathology, Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, MD, and Associate Professor, Department of Anatomy and Cell Biology, University of George Washington, Washington, DC
2004-Present Professor. The Greenebaum Cancer Center, Department of Pathology, The Center for Vascular and Inflammatory Diseases
Molecular oncology, metastasis, tumor invasion, receptor endocytosis, actin cytoskeleton, cell migration, signal transduction, and nanotechnology
- Li Y, Tondravi M, Liu J, Smith E, Haudenschild CC, Kaczmarek M, Zhan X (2001). Cortactin potentiates bone metastasis of breast cancer cells. Cancer Res 2001;61:6906-6911
- Uruno T, Liu J, Zhang P, Fan YX, Egile C, Li R, Mueller SC, Zhan X (2001). Activation of Arp2/3 complex-mediated actin polymerization by cortactin. Nat Cell Biol 2001;3:259-266.
- Uruno T, Liu J, Li Y, Smith, N, and Zhan X (2003). Sequential interaction of actin-related proteins 2 and 3 (Arp2/3) complex with neural Wiscott-Aldrich syndrome protein (N-WASP) and cortactin during branched actin filament network formation. J.Biol.Chem; 278: 26086-26093
- Yu D, Zhan HX, Zhao X, Williams M, Carey GB, Smith E, Su Y, Scott D, Zhu J, Guo Y, Cherukuri S, Civin CI, and Zhan X (2012). Mice deficient in MIM expression are predisposed to lymphomagenesis. Oncogene;31, 3561-358
- Zhan T, Cao C, Li L, Gu N, Civin CI, and Zhan X (2016). MIM regulates the trafficking of bone marrow cells via modulating surface expression of CXCR4. Leukemia. 29. 30, 1327-1334.
- Li, L., Baxter, S. S., Gu, N., Ji, M. & Zhan, X. Missing-in-metastasis protein downregulates CXCR4 by promoting ubiquitylation and interaction with small Rab GTPases. Journal of cell science 130, 1475-1485 (2017).
Metastasis is the major cause for the mortality of most cancer patients and encompasses at least two cell biological programs, an intracellular one that provides a mechanical force for cells to undergo shape changes, invade tissues, enter into the circulation, and exit from the circulation; and an extracellular one that provides a signal for the direction of disseminated tumor cells targeting at a specific site.
At the molecular level, the mechanic force is generated by the assembly of the monomeric actin into branched filaments at cell leading edges; whereas the directional signal is commonly carried by the gradient of a chemokine released from metastatic sites. One of the questions we have been interested is how tumor cells are endowed with an intrinsic ability to orchestrate these two programs in favor of their metastasis.
In the past decade, we have been focusing on two genes: cortactin and missing in metastasis (MIM or MTSS1), both of which are often aberrantly expressed in metastatic cells in an opposite manner. To understand the exact role of these two molecules in metastatic programs, we developed a variety of biochemical, cellular and animal models analyzing the properties of cortactin and MTSS1. Using these models, we demonstrated that cortactin is implicated in the assembly of actin filaments within the leading edge of motile cells.
We also evidenced that MTSS1 promotes membrane deformation and facilitates the internalization of receptors on the cell surface. We recently found that depletion of MTSS1 in mice favors malignant progression of B cells and modulates the trafficking of hematopoietic stem and progenitor cells through increasing the surface expression of CXCR4, a chemokine receptor that is crustal for the homeostasis of leukocytes and for organotropism of metastasis. The current of the research is centered on delineating the pathway for MTSS1 to regulate the response of tumor cells to chemokines and on exploring a potential to compromise metastasis by developing agents targeting this pathway.