Chemical and biochemical approaches in the study of signal transduction, gene regulation, and metabolism.
Our lab studies the chemical biology of protein post-translational modification and regulation. We study the structure, function, and regulation of protein kinases and protein phosphatases by phosphorylation, acetylation, and glycosylation. In this regard, we have developed a series of technologies including expressed protein ligation, chemical rescue of mutant enzymes, and bisubstrate analog inhibitors that we apply to the analysis of signaling proteins that help clarify substrate selectivity, activation state, and function. Our lab also studies histone acetyltransferases and demethylases and how they contribute to the regulation of gene expression and signaling. We have designed a series of selective inhibitors of these enzymes as tools for pharmacologic research. We employ and develop novel protein chemistry and proteomics methods including mass spectrometry to analyze the function of signaling enzymes on a broad scale. In addition, we are studying the mechanism and function of acyltransferases involved in circadian rhythm and metabolism using chemical biology strategies.
Hsiao PY, Kalin JH, Sun IH, Amin MN, Lo YC, Chiang MJ, Giddens J, Sysa-Shah P, Gabrielson K, Wang LX, Powell JD, Cole PA. An Fc-Small Molecule Conjugate for Targeted Inhibition of the Adenosine 2A Receptor. Chembiochem. 2016 PMID: 27432157.
Zucconi BE, Luef B, Xu W, Henry RA, Nodelman IM, Bowman GD, Andrews AJ, Cole PA. Modulation of p300/CBP Acetylation of Nucleosomes by Bromodomain Ligand I-CBP112. Biochemistry. 2016 PMID: 27332697.
Chen Z, Thomas SN, Bolduc DM, Jiang X, Zhang X, Wolberger C, Cole PA. Enzymatic Analysis of PTEN Ubiquitylation by WWP2 and NEDD4-1 E3 Ligases. Biochemistry. 2016 PMID: 27295432.
Chen Z, Dempsey DR, Thomas SN, Hayward D, Bolduc DM, Cole PA. Molecular Features of Phosphatase and Tensin Homolog (PTEN) Regulation by C-terminal Phosphorylation. J Biol Chem. 2016 PMID: 27226612.
Prusevich P, Kalin JH, Ming SA, Basso M, Givens J, Li X, Hu J, Taylor MS, Cieniewicz AM, Hsiao PY, Huang R, Roberson H, Adejola N, Avery LB, Casero RA Jr, Taverna SD, Qian J, Tackett AJ, Ratan RR, McDonald OG, Feinberg AP, Cole PA. A selective phenelzine analogue inhibitor of histone demethylase LSD1. ACS Chem Biol. 2014 PMID: 24707965.