Josiane Eid, M.D.
Assistant Professor of Cancer Biology
Vanderbilt-Ingram Cancer Center
740 Preston Building
Nashville, TN 37232
The main focus of our research is to explore nuclear signals that control key cytoplasmic events, such as signal transduction pathways and differentiation. If deregulated, these biological events could contribute to cancer development.
As a model, we are basing our studies on SYT-SSX, the translocation protein of synovial sarcoma, and its normal counterpart, the proto-oncoprotein SYT.
Synovial sarcoma is an aggressive soft tissue tumor that affects young adults. It is characterized by a chromosomal translocation between the SYT gene on chromosome 18 and the SSX gene on the X chromosome. As a result, a fusion protein, SYT-SSX, forms at the breakpoint. Since the X/18 rearrangement occurs in almost all cases of synovial sarcoma and is considered the hallmark of the cancer, SYT-SSX is thought to play a pivotal role in tumor formation
SYT and cell adhesion:
We have shown that during contact inhibition, SYT, when in complex with the nuclear transactivator p300, relays a nucleus-to-cytoplasm signal that allows the cell to undergo tight adhesion and spread on the extracellular matrix. Interfering with the integrity of the complex leads to a change in cell shape and its inability to adhere on fibronectin.
Contact inhibition is a fundamental biological event that prevents uncontrolled cell division. Proper cell adhesion is an important feature of contact inhibition, and tumor cells that lose their ability to contact inhibit become invasive and metastasize.
We are interested in studying the biological function of the proto-oncoprotein SYT in the control of cell adhesion during contact inhibition of growth and in controlling adhesive events and tissue architecture in 3D-cultures.
SYT-SSX and b-catenin/Wnt pathway:
We have recently found that the oncogene SYT-SSX induces translocation of b-catenin, the mediator of the Wnt pathway, into the nucleus, where both proteins appear to co-exist in a transcriptionally active complex.
we are currently investigating b-catenin function control by SYT-SSX and determining the pathway involved in this process. This will elucidate, in part, the mechanism of tumorigenesis by SYT-SSX.
SYT-SSX, SYT and chromatin remodeling:
Both SYT and SYT-SSX bind chromatin. they are thought to be involved in chromatin remodeling. We are applying proteomic as well as molecular biological analysis to determine and compare the contribution of both proteins in the control of gene expression and their effect on cell homeostatsis.
We are currently deciphering the role of SYT-SSX in polycomb repression.
Most recently, we have initiated a new research project that involves the role of NOTCH signaling in
synovial sarcoma development and self-renewal of mesenchymal progenitor/stem cells.
- Barco, R, Garcia, CB, Eid, JE The synovial sarcoma-associated SYT-SSX2 oncogene antagonizes the polycomb complex protein Bmi1. PLoS One, 4(4), e5060, 2009.
- Roy Barco, Christina B Garcia and Josiane Eid The synovial sarcoma-associated SYT-SSX2 oncogene antagonizes the polycomb complex protein Bmi1. PLoS ONE, 4(4), e5060, 2009.
- Kang, Y, Li, D, Kalams, SA, Eid, JE DC-Dielectrophoretic separation of biological cells by size. Biomed Microdevices, 10(2), 243-249, 2008 .
- Manesh Chittezhath, Andrea L Frump, Jerome Jourquin, Nichole Lobdell, Josiane Eid The proto-oncoprotein SYT (SS18) controls ATP release and regulates cyst formation by polarized MDCK cells. Experimental Cell Research, 314(19), 3551-3562, 2008 .
- Chittezhath, M, Frump, AL, Jourquin, J, Lobdell, N, Eid, JE The proto-oncoprotein SYT (SS18) controls ATP release and regulates cyst formation by polarized MDCK cells. Exp Cell Res, 314(19), 3551-62, 2008.
- Barco, R, Hunt, LB, Frump, AL, Garcia, CB, Benesh, A, Caldwell, RL, Eid, JE The synovial sarcoma SYT-SSX2 oncogene remodels the cytoskeleton through activation of the ephrin pathway. Mol Biol Cell, 18(10), 4003-12, 2007.
- Pretto, D, Barco, R, Rivera, J, Neel, N, Gustavson, MD, Eid, JE The synovial sarcoma translocation protein SYT-SSX2 recruits beta-catenin to the nucleus and associates with it in an active complex. Oncogene, 253661-3669, 2006.
- Eid, JE, Kung, AL, Scully, R, Livingston, DM p300 interacts with the nuclear proto-oncoprotein SYT as part of the active control of cell adhesion. Cell, 102(6), 839-48, 2000.
- Eid, JE, Sollner-Webb, B ST-2, a telomere and subtelomere duplex and G-strand binding protein activity in Trypanosoma brucei. J Biol Chem, 272(23), 14927-36, 1997.
- Eid, JE, Sollner-Webb, B ST-1, a 39-kilodalton protein in Trypanosoma brucei, exhibits a dual affinity for the duplex form of the 29-base-pair subtelomeric repeat and its C-rich strand. Mol Cell Biol, 15(1), 389-97, 1995.
- Eid, JE, Sollner-Webb, B Homologous recombination in the tandem calmodulin genes of Trypanosoma brucei yields multiple products: compensation for deleterious deletions by gene amplification. Genes Dev, 5(11), 2024-32, 1991.
- Eid, J, Sollner-Webb, B Stable integrative transformation of Trypanosoma brucei that occurs exclusively by homologous recombination. Proc Natl Acad Sci U S A, 88(6), 2118-21, 1991.
- Eid, JE, Ueno, H, Wang, CC, Donelson, JE Gossypol-induced death of African trypanosomes. Exp Parasitol, 66(1), 140-2, 1988.
- Eid, J, Sollner-Webb, B Efficient introduction of plasmid DNA into Trypanosoma brucei and transcription of a transfected chimeric gene. Proc Natl Acad Sci U S A, 84(22), 7812-6, 1987.
- Eid, J, Ebert, RF, Gesell, MS, Spivak, JL Intracellular growth factors in polycythemia vera and other myeloproliferative disorders. Proc Natl Acad Sci U S A, 84(2), 532-6, 1987.
- Josiane Eid, Christina B Garcia, Andrea Frump SSX2 (Synovial Sarcoma, X breakpoint 2). Atlas Genet Cytogenet Oncol Haematol, (April), 2008.