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Professor and Vice Chair,
Microbiology, Immunology & Molecular Genetics
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Director,
JCCC Signal Transduction and Therapeutics Program Area
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Research Director,
California NanoSystems Institute
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Education: |
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Degrees:
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Ph.D., Nagoya University, 1977
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Certifications: |
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Professional Societies:
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American Association for Cancer Research, American Association for Cancer Research
American Society for Biochemistry & Molecular Biology, American Society for Biochemistry & Molecular Biology
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Contact Information:
| Work Address: |
Office
2610C MSB
Los Angeles, CA 90095
UNITED STATES
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| Work Address: |
Laboratory
2711, 2715 MSB
Los Angeles, CA 90095
UNITED STATES
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| Work Address: |
2610C Mol Sci Bldg.
CAMPUS - 148906
CA
UNITED STATES
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Work Phone Number:
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(310) 206-7318
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Research Interests:
Identification of novel anti-cancer drugs and their nanodelivery
Recent advance in the study of the molecular basis of diseases led to the development of a new class of drugs that are mechanism based. We are currently generating novel anti-cancer drugs that are aimed at blocking lipid modification of membrane-bound molecular switches. These drugs are packaged into nanoparticles to achieve nanodelivery into cancer cells.
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Technical Research Interest:
Signal Transduction Inhibitors and Their Nanodelivery
Professor Tamanoi's group is interested in molecular switches and cellular signaling networks. The research focuses on the Ras family proteins that act as a nanoscale switch by shuttling between a GTP bound active form and a GDP-bound inactive form. Current research is aimed at characterizing two members of the Ras family proteins called Ras and Rheb. While Ras activates signaling pathways such as Raf/MAP kinase signaling, Rheb activates mTOR signaling that regulates protein synthesis. Overactivation of these molecular switches forms the basis of human diseases such as cancer, neurofibromatosis and tuberous sclerosis.
Another research focus is to carry out nanoscale modulation of the signaling network. To sccomplish this, small organic molecule compounds that can regulate the activity of molecular switches have been identified. One type of compound blocks their lipid modification resulting in the inhibition of their membrane association. Experiments are underway to package these compounds into nanoparticles and achieve nanodelivery into human cancer cells.
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Additional Information:
Fuyu Tamanoi is a biochemist who has served on the UCLA School of Medicine and UCLA College faculty since he joined the Department of Microbiology, Immunology & Molecular Genetics in 1993. He became a full professor in 1997. Since 1996, he has been a Director of Signal Transduction Program Area at Jonsson Comprehensive Cancer Center. Dr. Tamanoi earned his B.S. and M.S. in Biochemistry at the University of Tokyo. He received PhD in Molecular Biology at Nagoya University in 1977. He was a postdoctoral fellow at Harvard Medical School, where he worked on bacteriophage DNA replication. From 1980 to 1985, he was a senior staff investigator at Cold Spring Harbor Laboratory, where he worked on adenovirus DNA replication. From 1985 to 1993, he was an Assistant Professor and then Associate Professor at the University of Chicago, where he initiated studies on lipid modification of the Ras family proteins. His laboratory research centers on signal transduction and signal transduction inhibitors. He is currently exploring ways to deliver signal transduction inhibitors using nanoparticles.
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Kugawa, F. Suzuki, T. Miyata, M. Tomono, K. Tamanoi, F. , Construction of a model cell line for the assay of MDR1 (Multi Drug Resistance gene-1) substrates/inhibitors using HeLa cells, Pharmazie, 2009, 64 ( 5), 296-300.
Lu, J. Chan, L. Fiji, H. D. G. Dahl, R. Kwon, O. Tamanoi, F. , In vivo antitumor effect of a novel inhibitor of protein geranylgeranyltransferase-I, Molecular Cancer Therapeutics, 2009, 8 ( 5), 1218-1226.
Klichko, Y. Liong, M. Choi, E. Angelos, S. Nel, A. E. Stoddart, J. F. Tamanoi, F. Zink, J. I. , Mesostructured Silica for Optical Functionality, Nanomachines, and Drug Delivery, Journal of the American Ceramic Society, 2009, 92 ( 1), S2-S10.
Sato, T. Nakashima, A. Guo, L. Tamanoi, F. , Specific Activation of mTORC1 by Rheb G-protein in Vitro Involves Enhanced Recruitment of Its Substrate Protein, Journal of Biological Chemistry, 2009, 284 ( 19), 12783-12791.
Zhou, J. Vos, C. C. Gjyrezi, A. Yoshida, M. Khuri, F. R. Tamanoi, F. Giannakakou, P. , The Protein Farnesyltransferase Regulates HDAC6 Activity in a Microtubule-dependent Manner, Journal of Biological Chemistry, 2009, 284 ( 15), 9648-9655.
Short, J. D. Houston, K. D. Dere, R. Cai, S. L. Kim, J. Johnson, C. L. Broaddus, R. R. Shen, J. J. Miyamoto, S. Tamanoi, F. Kwiatkowski, D. Mills, G. B. Walker, C. L. , AMP-activated protein kinase signaling results in cytoplasmic sequestration of p27, Cancer Research, 2008, 68 ( 16), 6496-6506.
Sato, T. Umetsu, A. Tamanoi, F. , Characterization of the Rheb-mTOR signaling pathway in mammalian cells: Constitutive active mutants of Rheb and mTOR, Small Gtpases in Disease, Part A, 2008, 438, 307-320.
Ikeda, K. Morigasaki, S. Tatebe, H. Tamanoi, F. Shiozaki, K. , Fission yeast TOR complex 2 activates the AGC-family Gad8 kinase essential for stress resistance and cell cycle control, Cell Cycle, 2008, 7 ( 3), 358-364.
Watanabe, M. Fiji, H. D. G. Guo, L. Chan, L. Kinderman, S. S. Slamon, D. J. Kwon, O. Tamanoi, F. , Inhibitors of protein geranylgeranyltransferase I and Rab geranylgeranyltransferase identified from a library of allenoate-derived compounds, Journal of Biological Chemistry, 2008, 283 ( 15), 9571-9579.
Jie Lu, Eunshil Choi, Fuyuhiko Tamanoi, Jeffrey I. Zink , Light-Activated Nanoimpeller-Controlled Drug Release in Cancer Cells, Small , 2008, 4 (4), 421-426.
Liong, M. Lu, J. Kovochich, M. Xia, T. Ruehm, S. G. Nel, A. E. Tamanoi, F. Zink, J. I. , Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery, Acs Nano, 2008, 2 ( 5), 889-896.
Aspuria, P. J. Tamanoi, F. , The Tsc/Rheb signaling pathway controls basic amino acid uptake via the Cat1 permease in fission yeast, Molecular Genetics and Genomics, 2008, 279 ( 5), 441-450.
Lu, J. Liong, M. Zink, J. I. Tamanoi, F. , Mesoporous silica nanoparticles as a delivery system for hydrophobic anticancer drugs, Small, 2007, 3 ( 8), 1341-1346.
Castellano, S. Fiji, H. D. G. Kinderman, S. S. Watanabe, M. de Leon, P. Tamanoi, F. Kwon, O. , Small-molecule inhibitors of protein geranylgeranyltransferase type I, Journal of the American Chemical Society, 2007, 129 ( 18), 5843-+.
Aspuria, P. J. Sato, T. Tamanoi, F. , The TSC/Rheb/TOR signaling pathway in fission yeast and mammalian cells, Cell Cycle, 2007, 6 ( 14), 1692-1695.
Patel, P.H. and Tamanoi, F., Increased Rheb/TOR signaling enhances sensitivity of the whole organism to oxidative stress., J. Cell. Sci. , 2006 (119), 4285-4292.
Tabancay, A.P.Jr., Comiso, M.J. and Tamanoi, F., RAS family G-proteins in Saccharomyces cerevisiae and Schizosaccharomyces pombe., RAS family GTPases, 2006, 277-256.
Patel, P.H. and Tamanoi, F., Using Drosophila and yeast genetics to investigate a role for the Rheb GTPase in cell growth., Methods in Enzymol., 2006 (407), 443-454.
Khazak, V. Kato-Stankiewicz, J., Tamanoi, F, and Golemis, E.A. , Yeast screens for inhibitors of Ras-Raf interaction and characterization of MCP inhibitors of Ras-Raf interaction., Methods in Enzymol., 2006 (407), 612-629.
Gau CL, Kato-Stankiewicz J, Jiang C, Miyamoto S, Guo L and Tamanoi F , Farnesyltransferase inhibitors reverse altered growth and distribution of actin filaments in Tsc-deficient cells via inhibition of both rapamycin-sensitive and insensitive pathways. , Molecular Cancer Therapeutics, 2005, 4, 918-926.
Kho Y, Kim SC, Jiang C, Barma D, Kwon SW, Cheng J, Jaunbergs J, Weinbaum C, Tamanoi F, Falck J, Zhao Y, A tagging-via-substrate technology for detection and proteomics of farnesylated proteins., Proceedings of the National Academy of Sciences of the United States of America. , 2004, 101 (34), 12479-84.
Aspuria PJ, Tamanoi F, The Rheb family of GTP-binding proteins., Cellular signalling. , 2004, 16 (10), 1105-12.
Patel, P.H., Thapar, N., Guo, L., Martinez, M., Maris, J., Gau, C-L., Lengyel, J.A. and Tamanoi, F., Drosophila RHEB GTPase is required for cell cycle progression and cell growth., Journal of Cell Science, 2003 (116), 3601-3610.
Urano, J. Ellis, C. Clark, G. J. Tamanoi, F. , Characterization of Rheb functions using yeast and mammalian systems, Regulators and Effectors of Small Gtpases, Pt G, 2001, 333, 217-231.
Yang, W. L. Tabancay, A. P. Urano, J. Tamanoi, F. , Failure to farnesylate Rheb protein contributes to the enrichment of G0/G1 phase cells in the Schizosaccharomyces pombe farnesyltransferase mutant, Molecular Microbiology, 2001, 41 ( 6), 1339-1347.
Pervin, S. Singh, R. Gau, C. L. Edamatsu, H. Tamanoi, F. Chaudhuri, G. , Potentiation of nitric oxide-induced apoptosis of MDA-MB-468 cells by farnesyltransferase inhibitor: Implications in breast cancer, Cancer Research, 2001, 61 ( 12), 4701-4706.
Tamanoi, F. Gau, C. L. Jiang, C. Edamatsu, H. Kato-Stankiewicz, J. , Protein farnesylation in mammalian cells: effects of farnesyltransferase inhibitors on cancer cells, Cellular and Molecular Life Sciences, 2001, 58 ( 11), 1636-1649.
Finlin, B. S. Gau, C. L. Murphy, G. A. Shao, H. P. Kimel, T. Seitz, R. S. Chiu, Y. F. Botstein, D. Brown, P. O. Tamanoi, F. Andres, D. A. Perou, C. M. , RERG is a novel ras-related, estrogen-regulated and growth-inhibitory gene in breast cancer, Journal of Biological Chemistry, 2001, 276 ( 45), 42259-42267.
Guo, W. Tamanoi, F. Novick, P. , Spatial regulation of the exocyst complex by Rho1 GTPase, Nature Cell Biology, 2001, 3 ( 4), 353-360.
Edamatsu, H. Gau, C. L. Nemoto, T. Guo, L. Tamanoi, F. , Cdk inhibitors, roscovitine and olomoucine, synergize with farnesyltransferase inhibitor (FTI) to induce efficient apoptosis of human cancer cell lines, Oncogene, 2000, 19 ( 27), 3059-3068.
Chia, S. Y. Urano, J. Tamanoi, F. Dunn, B. Zink, J. I. , Patterned hexagonal arrays of living cells in sol-gel silica films, Journal of the American Chemical Society, 2000, 122 ( 27), 6488-6489.
Yang, W. L. Urano, J. Tamanoi, F. , Protein farnesylation is critical for maintaining normal cell morphology and canavanine resistance in Schizosaccharomyces pombe, Journal of Biological Chemistry, 2000, 275 ( 1), 429-438.
Urano, J. Tabancay, A. P. Yang, W. L. Tamanoi, F. , The Saccharomyces cerevisiae Rheb G-protein is involved in regulating canavanine resistance and arginine uptake, Journal of Biological Chemistry, 2000, 275 ( 15), 11198-11206.
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