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Lin CHENOffice Phone: 303 735 0071
E-mail: Lin.Chen@colorado.edu
FAX: 303 492 6194
Lab: Cristol Chemistry 241
Lab Phone: 303 492 4503
Group Website: http://keres.colorado.edu
Ph.D.: Harvard University, 1994
Structural Biology and Biochemistry
Our laboratory is interested in the structure and function of molecular complexes that control the specificity of signal transduction and transcription regulation inside cells. A major focus of our research is on calcium-mediated biological responses in immune, muscle and nervous systems. Two main pathways are being studied. One is the NFAT pathway regulated by calmodulin (CaM)-dependent calcineurin. The other is the MEF2 pathway regulated by CaM-dependent kinases (CaMK). We use X-ray crystallography and other biochemical methods to characterize molecular complexes of both pathways. Based on the structures, we make mutants to analyze further the functions of these complexes.
An important aspect of our research is to combine structural biology and chemical design to study the function of bio-macromolecular complexes. Specifically, we will attempt to develop cell permeable small molecule inhibitors of specific NFAT and MEF2 complexes to address further their functions in vivo. These studies have the potential to develop drugs for treating transplant rejection, heart diseases, and HIV infection.
Selected Publications
Lee T., Hoofnagle A.N., Stroud J., Min X., Goldsmith E.J., Chen L., Resing K.A., Ahn N.G., "Docking motif interactions in MAP kinases revealed by hydrogen exchange mass spectrometry", Mol. Cell, in press. 2004.
James C. Stroud and Lin Chen, "Structure of NFAT bound to DNA as a monomer", J. Mol. Biol., 334, 1009-1022, 2003.
Patrick G. Hogan, Lin Chen, Julie Nardone, and Anjana Rao, "Transcriptional regulation by calcium, calcineurin and NFAT",Genes & Development, 17, 2205-2232, 2003.
Guinevere A. Murphy, Erik Spedale, Sean Powell, Lorraine Pillus, Steve C. Schultz, Lin Chen, "The C-terminal coiled coil of Sir4p is required for telomeric and mating type loci silencing in S. cerevisiae", J. Mol. Biol. 334, 769-780, 2003.
Lei Jin, Piotr Sliz, Fernando Macian, Anjana Rao, Patrick Hogan, Lin Chen, Stephen C. Harrison, "An asymmetric NFAT1 dimer on a pseudo-palindromic KB-like DNA site", Nat. Struct. Biol., 807-11, 2003.
Michael J. Giffin, James C. Stroud, Darren Bates, Konstanze V. Koenig, Lin Chen, "Structure of NFAT1 bound to the HIV-1 LTR KB element as a cooperative dimer", Nat. Struct. Biol. 10, 800-6, 2003.
Dong U. Lee, Orly Avni, Lin Chen, Anjana Rao, "A distal enhancer in the IFN-gamma locus revealed by genome sequence comparison", J. Biol. Chem. 279, 4802-4810, 2003.
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