University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
David O. Morgan, PhD, FRS

David O. Morgan, PhD, FRS

Professor, Department of Physiology; Vice Dean for Research, School of Medicine, UCSF
Jack D. and De Loris Lange Chair in Physiology, UCSF

Cancer Center Program Memberships

Affiliate Member

Research Summary

My work focuses on a fundamental biological problem: understanding the regulatory system that guides the eukaryotic cell through the stages of the cell division cycle. My laboratory studies this problem primarily in the budding yeast Saccharomyces cerevisiae, but my findings have broad significance for human diseases, such as cancer, that arise from defects in cell proliferation or chromosome behavior. The research strategy of my laboratory is to use quantitative biochemical analysis to understand the detailed mechanisms of key enzymes involved in cell cycle control. We also use molecular genetics, proteomics, advanced light microscopy, and computational methods to explore how these enzymes are assembled into a robust regulatory system that drives accurate cell cycle progression and chromosome segregation.

Education

University of Calgary, Canada, B.Sc. (Hon.), 1980, Animal Biology
University of California San Francisco, Ph.D., 1986, Endocrinology
University of California San Francisco, Post-Doc, 1986-1989, Biochemistry


Professional Experience

  • 1981-1986
    Ph.D. student in Endocrinology, Department of Physiology, UCSF, with Richard A. Roth
  • 1986-1987
    Postdoctoral fellow with William J. Rutter, Department of Biochemistry & Biophysics, UCSF
  • 1987-1989
    Postdoctoral fellow with Harold E. Varmus, Department of Microbiology & Immunology, UCSF
  • 1989-1995
    Assistant Professor, Department of Physiology, UCSF. Joint appointment in Department of Biochemistry and Biophysics as of July, 1991
  • 1995-1997
    Associate Professor, Departments of Physiology and Biochemistry & Biophysics, UCSF
  • 1997-present
    Professor, Departments of Physiology and Biochemistry & Biophysics, UCSF
  • 7/98-present
    Vice-chair, Dept. of Physiology, UCSF
  • 1/13-present   
    Director, UCSF Tetrad Graduate Program.

Honors & Awards

  • 1987-1989
    Helen Hay Whitney Foundation Postdoctoral Fellowship
  • 1990-1993
    Searle Scholar Award
  • 1990-1992
    March of Dimes Basil O'Connor Starter Scholar Award
  • 1991-1996
    Rita Allen Foundation Scholar Award
  • 2007-present
    Jack D. and DeLoris Lange Endowed Chair in Physiology
  • 1997, 2003, 2006, 2008, 2010, 2012
    UCSF Medical School Teaching Award for Outstanding Lecture Series
  • 2010
    UCSF Kaiser Award for Excellence in Teaching in the Classroom Setting
  • 2010
    UCSF Graduate Students Association Outstanding Faculty Mentorship Award
  • 2011
    MERIT award, NIGMS
  • 2012
    Fellow, Royal Society of London

Selected Publications

  • De Bondt, H.L., Rosenblatt, J., Jancarik, J., Jones, H.D., Morgan, D.O., and Kim, S.-H. (1993) Crystal structure of cyclin-dependent kinase 2. Nature 363, 595-602.
  • Gu, Y., Turck, C.W., and Morgan, D.O. (1993) Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit. Nature 366, 707-710.
  • Fisher, R.P., and Morgan, D.O. (1994) A novel cyclin associates with MO15/CDK7 to form the CDK activating kinase. Cell 78, 713-724.
  • Shiekhattar, R., Mermelstein, F., Fisher, R.P., Drapkin, R., Dynlacht, B., Wessling, H.C., Morgan, D.O., and Reinberg, D. (1995) Cdk-activating kinase (CAK) complex is a component of human transcription factor IIH. Nature 374, 283-287.
  • Fisher, R.P., Jin, P., Chamberlin, H.M., and Morgan, D.O. (1995) Alternative mechanisms of CAK assembly require an assembly factor or an activating kinase. Cell 83, 47-57.
  • Espinoza, F.H., Farrell, A., Erdjument-Bromage, H., Tempst, P., and Morgan, D.O. (1996) A major cyclin-dependent-kinase-activating kinase (CAK) in budding yeast unrelated to vertebrate CAK. Science 273, 1714-1717.
  • Kim, K.-K., Chamberlin, H.M., Morgan, D.O., and Kim, S.-H. (1996) Three-dimensional structure of human cyclin H, a positive regulator of the CDK-activating kinase. Nature Structural Biology 3, 849-855.
  • Jin, P., Hardy, S., and Morgan, D.O. (1998) Nuclear localization of cyclin B1 controls mitotic entry after DNA damage. J. Cell Biol. 141, 875-885.
  • Jaspersen, S.L., Charles, J.F., Tinker-Kulberg, R.L., and Morgan, D.O. (1998) A late mitotic regulatory network controlling cyclin destruction in Saccharomyces cerevisiae. Mol. Biol. Cell 9, 2803-2817.
  • Jaspersen, S.L., Charles, J.F., and Morgan, D.O. (1999) Inhibitory phosphorylation of the APC regulator Hct1 is controlled by the kinase Cdc28 and the phosphatase Cdc14. Curr. Biol. 9, 227-236.
  • Takizawa, C.G., Weis, K., and Morgan, D.O. (1999) Ran-independent nuclear import of cyclin B1-Cdc2 by importin-beta. Proc. Natl. Acad. Sci. USA 96, 7938-7943.
  • Tinker-Kulberg, R., and Morgan, D.O. (1999) Pds1 and Esp1 control both anaphase and mitotic exit in normal cells and following DNA damage. Genes Dev. 13, 1936-1949.
  • Jaspersen, S.L., and Morgan, D.O. (2000) Cdc14 activates Cdc15 to promote mitotic exit in budding yeast. Curr. Biol. 10, 615-618.
  • Bishop, A.C., Ubersax, J.A., Petsch, D.T., Matheos, D., Gray, N.S., Blethrow, J., Shimizu, E., Tsien, J.Z., Schultz, P.G., Rose, M.D., Wood, J.L., Morgan, D.O., and Shokat, K.M. (2000) A chemical switch for inhibitor-sensitive alleles of any protein kinase. Nature 407, 395-401.
  • Garrett, S., Barton, W.A., Knights, R., Jin, P., Morgan, D.O., and Fisher, R.P. (2001) Reciprocal activation by CDK2 and CDK7 is directed by substrate specificity determinants outside the T-loop. Mol. Cell Biol. 21, 88-99.
  • Kraybill, B.C., Elkin, L.L., Blethrow, J.D., Morgan, D.O., and Shokat, K.M. (2002) Inhibitor scaffolds as new allele-specific kinase substrates. J. Amer. Chem. Soc. 124, 12118-12128.
  • Carroll, C.W., and Morgan, D.O. (2002) The Doc1 subunit is a processivity factor for the anaphase-promoting complex. Nat. Cell Biol. 4, 880-887.
  • Ubersax, J.A., Woodbury, E.L., Quang, P.N., Paraz, M., Blethrow, J.D., Shah, K., Shokat, K.M., and Morgan, D.O. (2003) Targets of the cyclin-dependent kinase Cdk1. Nature, 425, 859-864.
  • Carroll, C.W., Enquist-Newman, M., and Morgan, D.O. (2005) The APC subunit Doc1 promotes recognition of the substrate destruction box. Curr. Biol. 15, 11-18.
  • Loog, M., and Morgan, D.O. (2005) Cyclin specificity in the phosphorylation of cyclin-dependent kinase substrates. Nature 434, 104-108. (Commentary: Nature 434, 34-35; and Nat. Rev. Mol. Cell Biol. 6, 280)
  • Carroll, C.W., and Morgan, D.O. (2005) Enzymology of the Anaphase-Promoting Complex. Meth. Enzymol. 398, 219-230.
  • Thornton, B.R., Ng, T.M., Matyskiela, M.E., Carroll, C.W., Morgan, D.O., and Toczyski, D.P. (2006) An architectural map of the anaphase-promoting complex. Genes Dev. 20, 449-460.
  • Woodbury, E.L., and Morgan, D.O. (2007) Cdk and APC activities limit the spindle-stabilizing function of Fin1 to anaphase. Nat. Cell Biol. 9, 106-112.
  • Holt, L.J., Hutti, J.E., Cantley, L.C., and Morgan, D.O. (2007) Evolution of Ime2 phosphorylation sites on Cdk1 substrates provides a mechanism to limit the effects of the phosphatase Cdc14 in meiosis. Mol. Cell 25, 689-702.
  • Rodrigo-Brenni, M.C., and Morgan, D.O. (2007) Sequential E2s drive polyubiquitin chain assembly on APC targets. Cell 130, 127-139.
  • Goga, A., Tward, A., Morgan, D.O., and Bishop, J.M. (2007) Inhibition of Cdk1 as a potential therapy for tumors over-expressing MYC. Nature Medicine, 13, 820-827.
  • Blethrow, J.D., Glavy, J.S., Morgan, D.O., and Shokat, K.M. (2008) Covalent capture of kinase-specific phosphopeptides reveals novel Cdk1-cyclin B substrates. Proc. Natl. Acad. Sci. USA 105, 1442-1447.
  • Enquist-Newman, M., Sullivan, M., and Morgan, D.O. (2008) Modulation of the mitotic regulatory network by APC-dependent destruction of the Cdh1 inhibitor Acm1. Mol. Cell 30, 437-446.
  • Holt, L.J., Krutchinsky, A.N., and Morgan, D.O. (2008) Positive feedback sharpens the anaphase switch. Nature 454, 353-357.
  • Benanti, J.A., Matyskiela, M.E., Morgan, D.O., and Toczyski, D.P. (2009) Functionally distinct isoforms of Cik1 are differentially regulated by APC/C-mediated proteolysis. Mol. Cell 33, 581-590.
  • Matyskiela, M.E., and Morgan, D.O. (2009) Analysis of activator-binding sites on the APC/C supports a cooperative substrate-binding mechanism. Mol. Cell 34, 68-80.
  • Holt, L.J., Tuch, B.B., Villen, J., Johnson, A.D., Gygi, S.P., and Morgan, D.O. (2009) Global analysis of Cdk1 phosphorylation sites provides insights into evolution. Science 325, 1682-1686.
  • Rodrigo-Brenni, M.C., Foster, S.A., and Morgan, D.O. (2010) Catalysis of lysine 48-specific ubiquitin chain assembly by residues in E2 and ubiquitin. Mol. Cell 39, 548-559.