Yamamoto, Keith - University of California, San Francisco - Department of Chemistry and Chemical Biology

个人简介

Education: B.Sc. 1968 Biochemistry and Biophysics Iowa State University Ph.D. 1973 Biochemical Sciences Princeton University Research and Professional Activities: 1973-1975 Postdoctoral Fellow Department of Biochemistry and Biophysics University of California, San Francisco (UCSF) 1976-1979 Assistant Professor of Biochemistry Department of Biochemistry and Biophysics, UCSF 1979-1983 Associate Professor of Biochemistry Department of Biochemistry and Biophysics, UCSF 1983-2003 Professor of Biochemistry Department of Biochemistry and Biophysics, UCSF 1985-1994 Vice Chairman Department of Biochemistry and Biophysics, UCSF 1988-2001 Director Biochemistry and Molecular Biology Program Program in Biological Sciences, UCSF 1994– Professor Department of Cellular and Molecular Pharmacology, UCSF 1994-2003 Chairman Department of Cellular and Molecular Pharmacology, UCSF 2002-2003 Vice Dean for Research School of Medicine, UCSF 2004– Executive Vice Dean School of Medicine, UCSF 2011– Vice Chancellor for Research, UCSF

研究领域

Our lab studies members of the nuclear receptor (NR) superfamily, an essential class of metazoan transcriptional regulatory factors. Upon binding cognate hormones, we showed that the glucocoticoid receptor (GR), the founding member of the superfamily, binds to specific genomic sites termed glucocorticoid response elements (GREs), and activates or represses transcription of nearby target genes; regulation, it appeared, would be elegant and simple. Since those discoveries in the early 1980’s, we and others have come to appreciate that metazoan transcriptional regulation is indeed elegant, but far from simple. We now know, for example, that GREs are composite elements, comprised of specific GR binding sequences linked to gene-specific arrays of sequence motifs recognized by non-GR regulatory factors, and that response elements are nucleation centers for the dynamic assembly and disassembly of multifactor regulatory complexes containing gene-, cell- and physiologic state-specific combinations of roughly 102 different genome binding regulatory factors and coregulatory factors associated through protein:protein interactions. Two additional levels of combinatorial complexity, observed with GR and many other regulators, should be noted. First, “crosstalk”, in which unrelated regulatory factors affect each other’s activities, demonstrates that metazoan regulation is specified by nonlinear networks. Second, coregulators display a spectrum of different activities (recruitment of general transcription factors, addition or removal of histone marks, posttranslational modifications of nonhistone proteins, chromatin remodeling), implying that regulation from a given response element is likely comprised of multiple “layers” of different mechanisms.

近期论文

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Ratnappan, R., Amrit, F.R., Ward, J., Gill, H., Holden, K., Chen, S.-W., Olsen, C.P., Yamamoto, K.R., Ghazi, A. (2014) Germline signals deploy NHR-49/PPARa to modulate fatty-acid b-oxidation and desaturation in somatic tissues of c. elegans. PLoS Genetics. 10, e1004829. Ward, J.D., Yamamoto, K.R., Asahina, M. (2014) SUMO as a nuclear hormone receptor effector: New insights into combinatorial transcriptional regulation. Worm. 2, e29317. Schiller, B.J, Chodankar, R., Watson, L.C., Stallcup, M.R., Yamamoto, K.R. (2014) Glucocorticoid receptor binds half sites as a monomer and regulates specific target genes. Genome Biology. 15, 418. Ward, J.D., Mullaney, B., Schiller, B.J., He le, D., Petnic, S.E., Couillault, C., Pujol, N., Bernal, T.U., Van Gilst, M.R., Ashrafi, K., Ewbank, J.J., Yamamoto, K.R. (2014). Defects in the C. elegans acyl-CoA synthase, acs-3, and nuclear hormone receptor, nhr-25, cause sensitivity to distinct, but overlapping stresses. PLoS One. 20, e92552. Chokandar, R., Dai-Ying, W., Schiller, B.J., Yamamoto, K.R., Stallcup, M.R. (2014) Hic-5 is a transcription coregulator that acts before and/or after glucocorticoid receptor genome occupancy in a gene-selective manner. Proc Natl Acad Sci. USA. 111, 4007-12. Ward, J.D., Bojanala, N., Bernal, T., Ashrafi, A., Asahina, M. and Yamamoto, K.R. (2013) Sumoylated NHR-25/NR5A regulates cell fate during C. elegans vulval development. PLoS Genet. 9, e1003992. Thomas-Chollier, M., Watson, L.C., Cooper, S.B., Pufall, M.A., Liu, J.S., Borzym, K., Vingron, M., Yamamoto, K.R., Meijsing, S.H. (2013) A naturally occurring single amino acid insertion rewires transcriptional regulation by glucocorticoid receptor isoforms. Proc Natl Acad Sci USA. 110, 17826-31. Watson, L.C., Kuchenbecker, K.M., Schiller, B.J., Gross, J.D., Pufall, M.A., Yamamoto, K.R. (2013) The glucocorticoid receptor dimer interface allosterically transmits sequence-specific DNA signals. Nature Struc Mol Biol. 20, 876-83. Chen, S.-H., Masuno, K., Cooper, S., Yamamoto, K.R. (2013) An incoherent feed-forward regulatory logic underpinning glucocorticoid receptor action. Proc Natl Acad Sci USA. 110, 1964-9. Ziv, L., Muto, A., Schoonheim, P.J., Meijsing, S.H., Strasser, D., Ingraham, H.A., Schaaf, M.J.M., Yamamoto, K.R., Baier, H. (2012) An affective disorder in zebrafish with mutation of the glucocorticoid receptor. Mol. Psychiatry. doi: 10.1038/mp.2012.64. [epub ahead of print] Hood, L.E., Omenn, G.S., Moritz R.L., Aebersold, R., Yamamoto, K.R., Amos, M., Hunter-Cevera, J., Locascio, L.; Workshop Participants. (2012) New and improved proteomics technologies for understanding complex biological systems: addressing a grad challenge in the life sciences. Proteomics. 12, 2773-83. Engel K.B., Yamamoto K.R. (2011) The glucocorticoid receptor and the coregulator Brm selectively modulate each other’s occupancy and activity in a gene-specific manner. Mol. Cell. Biol. 31, 3267-76. pdf Holdorf, M.M., Cooper, S.B., Yamamoto, K.R., Miranda, J.J. (2011) Occupancy of chromatin organizers in the Epstein-Barr virus genome. Virology. 415, 1-5. Ou, C.-Y., LaBonte, M.J., Manegold, P.C., So, A. L., Ianculescu, I., Gerke, D.S., Yamamoto, K.R., Ladner, R.D., Kahn, M., Kim, J.-H., Stallcup, M.R. (2011) A coactivator role of CARM1 in the dysregulation of β-catenin activity in colorectal cancer cell growth and gene expression. Mol. Cancer Res. 9, 660-70. Cvoro, A., Yuan, C., Paruthiyil, S., Miller, O.H., Yamamoto, K.R., Leitman, D.C. (2011) Cross Talk between Glucocorticoid and Estrogen Receptors Occurs at a Subset of Proinflammatory Genes. J Immunol. 186, 4354-60. Costa, M.J., So, A.Y., Kaasik, K., Krueger, K.C., Pillsbury, M.L., Fu, Y.H., Ptacek, L.J., Yamamoto, K.R., Feldman, B.J. (2011) Circadian rhythm gene period 3 is an inhibitor of the adipocyte cell fate. J. Biol. Chem. 286, 9063-70.