Bardwell Lab

 

Principal investigator: Lee Bardwell

Department of Developmental and Cell Biology                                                                              

School of Biological Sciences

University of California, Irvine

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The Bardwell Lab is in the Department of Developmental and Cell Biology of the School of Biological Sciences at the University of California, Irvine.

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Research Interests

            Mechanisms of Specificity and Integration in Cell Signaling

The research in my laboratory is aimed at achieving an integrated molecular and systems-level understanding of the mechanisms by which intracellular signal transduction cascades execute a diverse repertoire of responses with efficiency and fidelity, and how this impacts human disease.  We focus not just on individual pathways, but also on the issues raised by the interactions of multiple pathways.  To this end, we study conserved signaling pathways controlling growth, development and stress responses in yeast and mammalian cells, using the techniques of molecular cell biology, biochemistry and biophysics, genetics and genomics, and mathematical & computational biology to address the fundamental questions of cell signaling and regulation.  We are particular motivated by trying to answer the following questions:

·       How do protein kinases find their correct substrates?  Can we predict new substrates?  Can we visualize kinase-substrate transactions in live cells?

·       How is specificity from signal to cellular response maintained when networks are highly interconnected, and different pathways use similar or overlapping components?

·       What evolutionary logic underlies the structure of signaling and gene regulatory networks?  Why are they so complicated and interconnected?  What performance objectives might these designs achieve?

·       How can we translate our increasingly sophisticated systems-level understanding of regulatory processes into new ideas for treating human disease?

Our present emphasis is on mitogen-activated protein kinase (MAPK) signaling pathways.  MAPK cascades participate in the regulation many biologically (and medically) important processes, including normal and pathological aspects of cell growth, division, differentiation, and death.  The ubiquity and versatility of MAPK cascades make them ideal for addressing the above questions.

See our publications to get a better idea of what we do.

More Research Details

Selected Recent Publications

  1. Bernardo, AS, Faial, T, Gardner, L, Niakan, KK, Ortmann, D, Senner, CE, Callery, EM, Trotter, MW, Hemberger, M, Smith, JC, Bardwell, L, Moffett, A, Pedersen, RA (2011)
    BRACHYURY and CDX2 mediate BMP-induced differentiation of human and mouse pluripotent stem cells into embryonic and extraembryonic lineages. 
    Cell Stem Cell, 9:144-55. Abstract
  2. Bardwell, L (2011)
    Synthetic Biology: Modulating the MAP kinase module.
    Current Biology, 21:R249-51.  Abstract
  3. TC Whisenant, DT Ho, RW Benz, JS Rogers, RM Kaake, EA Gordon, L Huang, P Baldi, L Bardwell (2010)
    Computational Prediction and Experimental Verification of New MAP Kinase Docking Sites and Substrates Including Gli Transcription Factors.
    PLoS Computational Biology 6:e10009084 Abstract  Download from PLoS
  4. S Haney, L Bardwell and Q Nie (2010)
    Ultrasensitive responses and specificity in cell signaling.
    BMC Systems Biology 4: 119. Abstract  Download from BMC
  5. X Liu, L Bardwell and Q Nie (2010)
    A combination of multisite phosphorylation and substrate sequestration produces switch-like responses.
    Biophysical Journal 98: 1396-407. Abstract
  6. AJ Bardwell, E Frankson and L Bardwell (2009)
    Selectivity of docking sites in MAPK kinases.
    Journal of Biological Chemistry 284: 13165-73. Abstract
  7. Z Hilioti, W Sabbagh Jr, S Paliwal, A Bergmann, MD Goncalves, L Bardwell, A Levchenko (2008)
    Oscillatory phosphorylation of yeast Fus3 MAP kinase controls periodic gene expression and morphogenesis.
    Current Biology 18:1700-6. Abstract
  8. L Bardwell (2008)
    Signal transduction: turning a switch into a rheostat.
    Current Biology 18:R910-2. Abstract
  9. L Bardwell,  X Zou, Q Nie and N Komarova (2007)
    Mathematical models of specificity in cell signaling.
    Biophysical Journal     92:3425-41. Abstract
  10. L Bardwell (2006)
    Mechanisms of MAPK signalling specificity.
    Biochemical Society Transactions     34:837-41. Abstract
  11. L Bardwell and K Shah (2006)
    Analysis of mitogen-activated protein kinase activation and interactions with regulators and substrates.
    Methods     40:213-23. Abstract
  12. DT Ho, AJ Bardwell, S Grewal, C Iverson and L Bardwell (2006)
    Interacting JNK-docking sites in MKK7 promote binding and activation of JNK mitogen-activated protein kinases.
    Journal of Biological Chemistry     281:13169-79. Abstract
  13. S Grewal, DM Molina and L Bardwell (2006)
    Mitogen-activated protein kinase (MAPK)-docking sites in MAPK kinases function as tethers that are crucial for MAPK regulation in vivo.
    Cellular Signalling     18:123-134. Abstract
  14. DM Molina, S Grewal and L Bardwell (2005)
    Characterization of an ERK-binding domain in MITF and differential inhibition of ERK2-mediated substrate phosphorylation.
    Journal of Biological Chemistry     280:42051-60. Abstract
  15. NL Komarova, X Zou, Q Nie and L Bardwell (2005)
    A theoretical framework for specificity in cell signaling.
    Molecular Systems Biology    , doi:10.1038/msb4100031, E1-E5. Online/pdf
  16. LJ Flatauer, S Zadeh and L Bardwell (2005)
    MAP Kinases With Distinct Requirements for Ste5 Scaffolding Influence Signaling Specificity in Yeast.
    Molecular and Cellular Biology     25: 1793-1803. Abstract -- Get pdf
  17. L Bardwell (2005)
    A walk-through of the yeast mating pheromone response pathway.
    Peptides     26 339-350. Abstract -- Download pdf
  18. PJ Cullen, W Sabbagh, M Irick, E Graham, E van Olden, C Neal, J Delrow, L Bardwell and GF Sprague, Jr. (2004)
    Msb2 is a Signaling Mucin at the Head of the Yeast Filamentous Growth MAPK Pathway.
    Genes & Development     18:1695-1708. Abstract
  19. AB Kusari, DM Molina, W Sabbagh Jr., C Lau and L Bardwell (2004)
    A conserved protein interaction network involving the yeast MAP kinases Fus3 and Kss1.
    Journal of Cell Biology     164:267-277. Abstract -- Get pdf
  20. AJ Bardwell, M Abdollahi and L Bardwell (2004)
    Anthrax lethal factor-cleavage products of mitogen-activated protein kinase (MAPK) kinases exhibit reduced binding to their cognate MAPKs.
    Biochemical Journal     378:569-577. Abstract -- Get pdf
  21. DT Ho, AJ Bardwell, M Abdollahi and L Bardwell (2003)
    A docking site in MKK4 mediates high-affinity binding to JNK MAP kinases and competes with similar docking sites in JNK substrates
    Journal of Biological Chemistry     278:32662-72. Abstract
  22. AJ Bardwell, M Abdollahi and L Bardwell (2003)
    Docking sites on mitogen-activated protein kinase (MAPK) kinases, MAPK phosphatases and the Elk-1 transcription factor compete for MAPK binding and are crucial for enzymic activity
    Biochemical Journal     370:1077-1085. Abstract
  23. W Sabbagh Jr, LJ Flatauer, AJ Bardwell and L Bardwell (2001)
    Specificity of MAPK signaling in yeast differentiation involves transient vs. sustained MAPK activation
    Molecular Cell     8:683-691. Abstract
  24. AJ Bardwell, LJ Flatauer, K Matsukuma, J Thorner and L Bardwell (2001)
    A conserved docking site in MEKs mediates high-affinity binding to MAP kinases and cooperates with a scaffold protein to enhance signal transmission
    Journal of Biological Chemistry     276:10374-10386. Abstract

More Publications

Last modified 20 August 2011. Back to top