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.

Research Funding

  • May 1, 2016 - April 30, 2026 - Regulatory Enzymes and Systems in Cell Cycle Control , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R35GM118053
  • July 1, 1979 - June 30, 2021 - Cell Biology, Genetics, and Biochemistry Training Grant , Principal Investigator . Sponsor: NIH, Sponsor Award ID: T32GM007810
  • January 1, 2004 - March 31, 2017 - Cell Cycle Control by Cyclin-Dependent Kinases , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM069901
  • August 3, 1990 - August 31, 2016 - Molecular Control of Cell Proliferation , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R37GM053270

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

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

  1. Hartooni N, Sung J, Jain A, Morgan DO. Single-molecule analysis of specificity and multivalency in binding of short linear substrate motifs to the APC/C. Nat Commun. 2022 01 17; 13(1):341.  View on PubMed
  2. Asfaha JB, Örd M, Carlson CR, Faustova I, Loog M, Morgan DO. Multisite phosphorylation by Cdk1 initiates delayed negative feedback to control mitotic transcription. Curr Biol. 2022 Jan 10; 32(1):256-263.e4.  View on PubMed
  3. Yu J, Raia P, Ghent CM, Raisch T, Sadian Y, Cavadini S, Sabale PM, Barford D, Raunser S, Morgan DO, Boland A. Structural basis of human separase regulation by securin and CDK1-cyclin B1. Nature. 2021 08; 596(7870):138-142.  View on PubMed
  4. Carlson CR, Asfaha JB, Ghent CM, Howard CJ, Hartooni N, Safari M, Frankel AD, Morgan DO. Phosphoregulation of Phase Separation by the SARS-CoV-2 N Protein Suggests a Biophysical Basis for its Dual Functions. Mol Cell. 2020 12 17; 80(6):1092-1103.e4.  View on PubMed
  5. Carlson CR, Asfaha JB, Ghent CM, Howard CJ, Hartooni N, Morgan DO. Phosphorylation modulates liquid-liquid phase separation of the SARS-CoV-2 N protein. bioRxiv. 2020 Jun 29.  View on PubMed
  6. Mizrak A, Morgan DO. Polyanions provide selective control of APC/C interactions with the activator subunit. Nat Commun. 2019 12 20; 10(1):5807.  View on PubMed
  7. Rosen LE, Klebba JE, Asfaha JB, Ghent CM, Campbell MG, Cheng Y, Morgan DO. Cohesin cleavage by separase is enhanced by a substrate motif distinct from the cleavage site. Nat Commun. 2019 11 15; 10(1):5189.  View on PubMed
  8. Qin L, Mizrak A, Guimarães DSPSF, Tambrin HM, Morgan DO, Hall MC. The pseudosubstrate inhibitor Acm1 inhibits the anaphase-promoting complex/cyclosome by combining high-affinity activator binding with disruption of Doc1/Apc10 function. J Biol Chem. 2019 11 15; 294(46):17249-17261.  View on PubMed
  9. Seoane AI, Morgan DO. Firing of Replication Origins Frees Dbf4-Cdc7 to Target Eco1 for Destruction. Curr Biol. 2017 Sep 25; 27(18):2849-2855.e2.  View on PubMed
  10. Davey NE, Morgan DO. Building a Regulatory Network with Short Linear Sequence Motifs: Lessons from the Degrons of the Anaphase-Promoting Complex. Mol Cell. 2016 10 06; 64(1):12-23.  View on PubMed
  11. Galli M, Morgan DO. Cell Size Determines the Strength of the Spindle Assembly Checkpoint during Embryonic Development. Dev Cell. 2016 Feb 08; 36(3):344-52.  View on PubMed
  12. Lu D, Girard JR, Li W, Mizrak A, Morgan DO. Quantitative framework for ordered degradation of APC/C substrates. BMC Biol. 2015 Nov 16; 13:96.  View on PubMed
  13. Girard JR, Tenthorey JL, Morgan DO. An E2 accessory domain increases affinity for the anaphase-promoting complex and ensures E2 competition. J Biol Chem. 2015 Oct 02; 290(40):24614-25.  View on PubMed
  14. Lu D, Hsiao JY, Davey NE, Van Voorhis VA, Foster SA, Tang C, Morgan DO. Multiple mechanisms determine the order of APC/C substrate degradation in mitosis. J Cell Biol. 2014 Oct 13; 207(1):23-39.  View on PubMed
  15. Eshleman HD, Morgan DO. Sgo1 recruits PP2A to chromosomes to ensure sister chromatid bi-orientation during mitosis. J Cell Sci. 2014 Nov 15; 127(Pt 22):4974-83.  View on PubMed
  16. Van Voorhis VA, Morgan DO. Activation of the APC/C ubiquitin ligase by enhanced E2 efficiency. Curr Biol. 2014 Jul 07; 24(13):1556-62.  View on PubMed
  17. Naylor SG, Morgan DO. Cdk1-dependent phosphorylation of Iqg1 governs actomyosin ring assembly prior to cytokinesis. J Cell Sci. 2014 Mar 01; 127(Pt 5):1128-37.  View on PubMed
  18. Morgan DO. The D box meets its match. Mol Cell. 2013 Jun 06; 50(5):609-10.  View on PubMed
  19. Lyons NA, Fonslow BR, Diedrich JK, Yates JR, Morgan DO. Sequential primed kinases create a damage-responsive phosphodegron on Eco1. Nat Struct Mol Biol. 2013 Feb; 20(2):194-201.  View on PubMed
  20. Foster SA, Morgan DO. The APC/C subunit Mnd2/Apc15 promotes Cdc20 autoubiquitination and spindle assembly checkpoint inactivation. Mol Cell. 2012 Sep 28; 47(6):921-32.  View on PubMed

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