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 methods.
Research in the transcription area focuses on novel roles of the proteasome in gene expression. In particular we are interested in understanding the mechanistic basis of our recent finding that a sub-complex of the proteasome plays a critical, but non-proteolytic, role in RNA polymerase II elongation.
Our proteomics efforts are directed towards developing new techniques, with an emphasis on chemical methods, and applying these technologies to the study of important receptor-initiated signaling pathways. For example, we have developed novel visible light-triggered cross-linking chemistry that is far more efficient than traditional methods and are using this to map the architecture of multi-protein complexes. A major effort is underway to develop protein-detecting microarrays based on synthetic capture agents. We have recently made a breakthrough in the isolation of very high affinity protein ligands from combinatorial libraries of peptide and peptide-like compounds. Finally, we are employing a number of methods to develop genome-wide transcription factor-DNA binding maps that should complement traditional microarray-based expression analysis in understanding how cells respond to mutations or stimuli.
