Lee Bardwell

Professor, Developmental & Cell Biology
School of Biological Sciences

PH.D., Stanford University, 1992


B.A., Wesleyan University, CT, 1984

Phone: (949) 824-6902
Fax: (949) 824-4709
Email: bardwell@uci.edu

University of California, Irvine
Dept. of Developmental & Cell Biology
5207 McGaugh Hall
Mail Code: 2300
Irvine, CA 92697

picture of Lee  Bardwell

Research
Interests
How cell signaling networks work, and how they achieve specificity.
   
URL www.dbc.uci.edu/~bardwell/
   
Academic
Distinctions
2004-05 National Academies of Sciences Keck Futures Initiative Grantee
1999-02 Beckman Young Investigator Award, Beckman Foundation
1999-02 New Investigator Award - Pharmacological Sciences, Burroughs Wellcome Fund
1997-00 Special Fellow Award, Leukemia Society of America
1993-96 NIH National Research Service Award Postdoctoral Fellowship
1987-91 Predoctoral Training Grant, National Cancer Institute
1984 Phi Beta Kappa
1984 Sigma Xi
   
Appointments 1993-98 Postdoctoral Fellow, University of California, Berkeley (Laboratory of Prof. Jeremy Thorner)
   
Research
Abstract
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.
   
Publications 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.
   
  Bardwell, L (2011)
Synthetic Biology: Modulating the MAP kinase module.
Current Biology, 21:R249-51.
   
  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
   
  S Haney, L Bardwell and Q Nie (2010)
Ultrasensitive responses and specificity in cell signaling.
BMC Systems Biology 4: 119.
   
  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.
   
  AJ Bardwell, E Frankson and L Bardwell (2009)
Selectivity of docking sites in MAPK kinases.
Journal of Biological Chemistry 284: 13165-73.
   
  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.
   
  L Bardwell (2008)
Signal transduction: turning a switch into a rheostat.
Current Biology 18:R910-2.
   
  My latest publications are listed on my lab website:

http://www.dbc.uci.edu/~bardwell/
   
Grants NIH - R01 GM60366 (PI: Bardwell) “MAP Kinase Cascade Signal Transmission and Specificity"
   
NIH - R33 GM69013 (PI: E. Mjolsness), “A Signal Transduction Pathway Database/Modeling System”
   
National Academies Keck Futures Initiative (PI: Bardwell) “Intracellular Signaling Specificity: Theoretical and Computational Explorations”
   
(This is just a partial listing of past and present grants.)
   
Graduate Programs Cellular and Molecular Biosciences

Mathematical and Computational Biology

Biotechnology

   
Research Centers UCI/Chao Family Cancer Center
   
UCI Institute for Genomics and Bioinformatics
   
UCI Developmental Biology Center
   
UCI Center for Complex Biological Systems
   
   
Link to this profile http://www.faculty.uci.edu/profile.cfm?faculty_id=4549
   
Last updated 01/24/2012