2208 Natural Sciences I
University of California Irvine
Irvine, CA 92697
Tel: (949) 824-6902
Fax: (949) 824-4709
Website: Lab Homepage
Cell Signaling – We study conserved signaling pathways controlling growth, development and stress responses in yeast and mammalian cells. We use techniques from molecular cell biology, biochemistry and biophysics, genetics and genomics, and mathematical & computational biology to address fundamental questions of cell signaling and regulation. We are particular motivated by trying to answer the following questions:
- How do protein kinases find their substrates? Can we use this knowledge to identify new substrates and regulatory strategies, and to find new ways to treat cancer and other diseases?
- 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?
- Can we combine biochemistry, genetics, math/computation and cutting-edge imaging to visualize, model and understand what really happens in space and time during intracellular signal transduction?
- 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.
- Compani, B, Su, T, Chang, I, Cheng, J, Shah, K, Whisenant, T, Dou, Y, Bergmann, A, Cheong, R, Bardwell, L, Levchenko, A, Baldi, P, Mjolsness, E (2010) A Scalable and Integrative System for Pathway Bioinformatics and Systems Biology. Adv. Exp. Med. Biol., 680:523-534
- Whisenant, TM, Benz, R, Ho, DM, Rogers, JM, Kaake, RM, Gordon, EA, Huang, L, Baldi, P, and Bardwell, L (2010) Computational prediction and experimental verification of novel MAP kinase substrates including Gli transcription factors. PLoS Computational Biology, 6:e10009084.
- Haney, S., Bardwell, L+, and Nie, Q+ (2010) Ultrasensitive responses and specificity of cell signaling. BMC Systems Biology, 4:119.
- Liu, X, Bardwell, L+ and Nie, Q+ (2010) A combination of multisite phosphorylation and substrate sequestration produces switch-like responses. Biophysical Journal, 98:1396-407.
- Bardwell, AJ, Frankson, E and Bardwell, L (2009) Selectivity of docking sites in MAPK kinases. J. Biol. Chem. 284:13165-73.