Philip Cole, M.D., Ph.D.

We use chemical approaches to study cell signal transduction hormonal control of circadian rhythm and gene regulation. We are interested in understanding the basis for molecular recognition of protein kinases. We employ substrate analogs, site-directed mutagenesis, and kinetic methods to elucidate protein kinase-substrate relationships. We are also pursuing the mechanism and inhibition of melatonin production. A new protein engineering method called expressed protein ligation, which allows for the ligation of synthetic peptides to recombinant proteins developed by us in collaboration with Tom Muir's laboratory, is being applied to these systems and others to elucidate protein function. We have also developed selective HAT (histone acetyltransferase) and demethylase inhibitors to investigate the role of the protein acetylation and methylation.