Professor and Director
Department of Pharmacology and Molecular Sciences
School of Medicine

pcole@jhmi.edu

316 Hunterian Building
725 N. Wolfe Street
Baltimore, MD 21205

Office: 410-614-0540
Lab: 410-955-0322

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.

Selected Publications
Liu, X., L. Wang, K. Zhao, P.R. Thompson, Y. Hwang, R. Marmorstein, and P.A. Cole. (2008) The structural basis of protein acetylation by the p300/CBP transcriptional coactivator. Nature 451:846-850.

Pickin, K.A., S. Chaudhury, B.C.R. Dancy, J.J. Gray, and P.A. Cole. (2008) Analysis of autophosphorylation of a protein kinase by expressed protein ligation. J. Am. Chem. Soc. 130:5667-5669.

Hwang, Y., P.R. Thompson, L. Wang, L. Jiang, N.L. Kelleher, and P.A. Cole. (2007) A selective chemical probe for coenzyme-A requiring enzymes. Angew. Chem. Int. Ed. 46:7621-7624.

Karanam, B., L. Wang, D. Wang, X. Liu, R. Marmorstein, R. Cotter, and P.A. Cole. (2007) Multiple roles for acetylation in the interaction of p300 HAT with ATF-2. Biochemistry 46:8207-8216.

Yang, M., J.C. Culhane, L.M. Szewczuk, C.B. Gocke, C.A. Brautigam, D.R. Tomchick, M. Machius, P.A. Cole, and H. Yu. (2007) Structural basis of histone demethylation by LSD1 revealed by suicide inactivation. Nat. Struct. Mol. Biol. 14:535-539.

Qiao, Y., H. Molina, A. Pandey, J. Zhang, and P.A. Cole. (2006) Chemical rescue of a mutant enzyme in living cells. Science 311:1293-1297.

Schwarzer, D., Z. Zhang, W. Zheng, and P.A. Cole. (2006) Negative regulation of a tyrosine phosphatase by tyrosine phosphorylation. J. Am. Chem. Soc. 128:4192-4193.

Culhane, J.C., L.M. Szewczuk, X. Liu, G. Da, R. Marmorstein, and P.A. Cole. (2006) A mechanism-based inactivator for histone demethylase LSD1. J. Am. Chem. Soc. 128:4356-4357.

Zhang, X., J. Gureasko, K. Shen, P.A. Cole, and J. Kuriyan. (2006) An allosteric mechanism for the activation of the kinase domain of the epidermal growth factor receptor. Cell 125:1137-1149.