The Kodadek laboratory works in the general field of chemical biology. Our research encompasses two broad areas: 1) the enzymology and regulation of eukaryotic gene expression, and 2) proteomics. All of the ongoing projects employ a wide array of techniques, including molecular biology, protein biochemistry, organic and inorganic chemistry and many biophysical techniques.
Research in the transcription area focuses on novel roles of the proteasome in gene expression. We have discovered that the proteasome and its sub-complexes play a variety of both proteolytic and non-proteolytic roles in RNA polymerase II-mediated gene expression, including: 1) stimulating promoter escape and elongation, 2) regulating the lifetime of transcription factor-promoter interactions and 3) resolving stalled RNA polymerase-template complexes. The mechanistic underpinnings of all of these events and their impact on the regulation of gene expression are under investigation.
Our proteomics efforts are directed towards the development of new chemical techniques to monitor and manipulate protein activities and interactions. Specific projects include: 1) the development of protein-detecting microarrays based on synthetic peptides and peptoids, 2) new protein cross-linking and analysis methods for the elucidation of protein-protein interactions in complexes, 3) development of cell-based assays for the identification of neuroactive compounds, particularly species that recognize receptors important in sleep homeostasis.
RESEARCH INTERESTS
Chemical Biology
Proteomics
Transcription Regulation
RECENT PUBLICATIONS
Lim, H.-Y., Archer, C.T. and Kodadek, T., "Identification of a peptoid inhibitor of the proteasome 19S regulatory particle" J. Amer. Chem. Soc., 129:7750-7751, Summer 2007
Xiao, X., Yu, P., Lim, H.-S., Sikder, D. and Kodadek, T., "A cell permeable transcription factor mimic" Angew. Chem. Intl. Ed., 46:2865-2868, Spring 2007
Ferdous, A., Sikder, D., Gillette, T., Nalley, K., Kodadek, T. and Johnston, S.A., "The Role of the Proteasomal ATPases and Activator Mono-Ubiquitylation in Regulating Gal4 Binding to Promoters" Genes & Development, 21:112-123, January 2007
Nalley, K., Johnston, S.A. and Kodadek, T., "Proteolytic turnover of Gal4 is not required for function in vivo" Nature, 442:1054-1057, Spring 2006
Reddy, M.M. and Kodadek, T., "Protein fingerprinting in complex mixtures using peptoid microarrays" Proc. Natl. Acad. Sci. USA, 102:12672-12677, Fall 2005
SIGNIFICANT PUBLICATIONS
Sikder, D., Johnston, S.A. and Kodadek, T., "Widespread, but non-identical, association of proteasomal 19S and 20S proteins with yeast chromatin" J. Biol. Chem., 281:27346-27355, September 2006
Kodadek, T., Sikder, D. and Nalley, K., "Keeping transcriptional activators under control" Cell, 127:261-264, October 2006
Fancy, D.A., Kodadek, T., "Chemistry for the analysis of protein-protein interactions: Rapid and efficient cross-linking triggered by long wavelength light" Proc. Natl. Acad. Sci. USA, 96:6020-6024
Gonzalez, F., Delahoude, A., Kodadek, T. and Johnston, S.A., "A sub-complex of the 19S proteasome regulatory complex is recruited to an activated promoter" Science, 296:548-550
Alluri, P.G. Reddy, M.M., Bacchawat-Sikder, K., Olivos, H.J. and Kodadek, T., "Isolation of protein ligands from large peptoid libraries" J. Amer. Chem. Soc., 125:13995-14004, Summer 2003
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