Cancer Institute

  • Guri Tzivion

    tzivion_guri.jpgAssociate Professor, Department of Biochemistry
    Tumor Cell Biology Program
    PhD, Immunology, 1995, Hebrew University, Jerusalem
    Postdoc, 1995-2000, Massachusetts General Hospital, Boston MA

    Contact information
    2500 N State St., Room G759
    Jackson, MS 39216
    Phone: (601) 815-6765
    Fax: (601) 815-6806

    Research interests

    • Intracellular signaling pathways involved in regulation of cancer and aging
    • Ras-Raf-MAPK, AKT-FoxO and Nicotinamide-Sirtuin pathways
    • 14-3-3 proteins

    Research synopsis

    The broad goal of our research is to understand signaling processes and networking downstream of growth factor receptors at molecular and mechanistic levels and to apply this knowledge to address cancer and lifespan related problems. Intracellular signaling pathways are required for the regulation of many physiological processes under normal conditions, however, when deregulated, can result in various pathological conditions, primarily cancer. For instance, increased activation of growth factor receptors and mutations in downstream signaling molecules such as Ras, Raf and PI3K are associated with more than half of all human cancers. The study of signaling pathways allowed the recent development of targeted therapies such as Gleevec, targeting abl, Herceptin, targeting Her2 and Sorafenib, targeting Raf and the VEGF receptor. Specifically, our program involves defining functional and regulatory aspects of four distinct pathways in cancer and lifespan control through employing molecular and biochemical methodologies combined with transgenic mice models. These pathways include the Ras-Raf-MAPK pathway, the PI3K-AKT-FoxO pathway, 14-3-3-regulated pathways and the nicotinamide-sirtuin pathway. It is broadly accepted today that understanding the complex nature of intracellular signaling pathways and their intricate signaling networks will have significant clinical benefits by identifying new candidates for therapeutic intervention and by devising combination therapies. The Ras-Raf-MAPK and the PI3K-AKT-FoxO pathways are good examples, showing positive and negative feedback regulations within the cascade as well as cross-talk relations with each other. The significance of the integration of signals through these pathways is emphasized by the apparent need to inhibit both pathways for effective cancer growth attention.

    Recent accomplishments and honors

    • 2011Guest Editor, PI3K-AKT-FoxO axis in cancer and aging. BBA-Molecular Cell Research 1813, 1925-1986, 2011.
    • 2008 Session Chair, Gordon Research Conference on Biology of 14-3-3 Proteins, Ventura, CA, February 24-29.

    • 2007 Guest Editor, Mitogen-Activated Protein Kinases; New insights on regulation, function and role in human disease. BBA, Molecular Cell Research 1773, 1149-1388, 2007.

    Selected publications

    • Leicht DT, Balan V, Zhu J, Kaplun A, Bronisz A, Rana A and Tzivion G. MEK-1 activates C-Raf through a Ras-independent mechanism. BBA-Molecular Cell Research 1833, 976-986, 2013. PMC3608709
    • Rangasamy V, Mishra R, Sondarva G, Das S, Lee TH, Bakowska JC, Tzivion G, Malter JS, Rana B, Lu KP, Kanthasamy A and Rana A. Mixed-lineage kinase 3 phosphorylates prolyl-isomerase Pin1 to regulate its nuclear translocation and cellular function. PNAS 109, 8149-8154, 2012. PMC3361382
    • Dobson M, Ramakrishnan G, Ma S, Kaplun L, Balan V, Fridman R and Tzivion G. Bimodal regulation of FoxO3 by AKT and 14-3-3. BBA-Molecular Cell Research 1813, 1453–1464, 2011. PMC3237389
    • Balan V, Miller G, Kaplun L, Balan K, Chong Z, Li F, Kaplun A, VanBerkum MFA, Arking R, Freeman DC, Maiese K and Tzivion G. Lifespan extension and neuronal cell protection by Drosophila nicotinamidase. JBC 283, 27810-27819, 2008. PMC2562057
    • Balan V, Leicht DT, Zhu J, Balan K, Kaplun A, Singh-Gupta V, Qin J, Ruan H, Comb MJ and Tzivion G. Identification of novel in vivo Raf-1 phosphorylation sites mediating positive feedback Raf-1 regulation by ERK. Mol Biol Cell 17, 1141-1153, 2006. PMC1382304
    • Zhu J, Balan V, Bronisz A, Balan K, Sun H, Leicht DT, Luo Z, Qin J, Avruch J and Tzivion G. Identification of Raf-1 S471 as a novel phosphorylation site critical for Raf-1 and B-Raf kinase activities and for MEK binding. Mol Biol Cell 16, 4733-4744, 2005. PMC1237079
    • Shen YH, Godlewski J, Bronisz A, Zhu J, Comb MJ, Avruch J and Tzivion G. Significance of 14-3-3 self-dimerization for phosphorylation-dependent target binding. Mol Biol Cell 14, 4721-4733, 2003. PMC266786
    • Shen YH, Godlewski J, Zhu J, Sathyanarayana P, Leaner V, Birrer MJ, Rana A and Tzivion G. Cross talk between JNK/SAPK and ERK/MAPK pathways: Sustained activation of JNK blocks ERK activation by EGF. JBC 278, 26715-26721, 2003. PMID: 12738796
    • Tzivion G, Luo Z and Avruch J. A dimeric 14-3-3 protein is an essential cofactor for Raf kinase activity. Nature 394, 88-92, 1998. PMID: 9665134
    • Luo Z*, Tzivion G*, Belshaw PJ, Vavvas D, Marshall M and Avruch J. Oligomerization activates c-Raf-1 through a Ras-dependent mechanism. Nature 383, 181-185, 1996. PMID: 8774885