Picture of Phil Cole

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

Professor of Medicine and Biological Chemistry and Molecular Pharmacology

Our research involves the chemical biology of protein post-translational modifcations (PTMs) in the context of signaling, epigenetics, and cancer.  We develop and apply chemical approaches including protein semisynthesis and small molecule probes to the study of protein phosphorylation, acetylation, ubiquitination, and other PTMs in enzymes and cellular networks. 

Phil Cole graduated from Yale University with a B.S. in Chemistry in 1984 and then spent a year as a Churchill Scholar at the University of Cambridge.  Cole went on to obtain M.D. and Ph.D. degrees from Johns Hopkins where he pursued research in bioorganic chemistry in 1991.  Cole then entered clinical and post-doctoral training at Brigham and Women's Hospital and Harvard Medical School prior to joining Rockefeller University in 1996 as a junior lab head.  In 1999, Cole returned to Johns Hopkins as professor and director of pharmacology where he served until 2017, when he moved to Harvard Medical School and Brigham and Women's Hospital as professor of medicine and biological chemistry and molecular pharmacology.  His research interests are in the area of chemical biology, protein post-translational modifications, cell signaling, and epigenetics.

Research:

Our research involves the chemical biology of protein post-translational modifcations (PTMs) in the context of signaling, epigenetics, and cancer.  We develop and apply chemical approaches including protein semisynthesis and small molecule probes to the study of protein phosphorylation, acetylation, ubiquitination, and other PTMs in enzymes and cellular networks.  We are currently investigating the functions, regulation, and mechanisms of PTEN lipid phosphatase, Akt protein kinase, NEDD4 ubiquitin ligases, LSD1 histone demethylase, HDAC1 deacetylase, the CoREST complex, and p300/CBP acetyltransferase.  We strive to translate our findings in signaling and epigenetics to identify novel therapeutic opportunities for the treatment of cancer and other diseases.

Address: 

New Research Building

77 Avenue Louis Pasteur

Room 168C

Boston, MA 02115

Publications View
Investigation into the use of histone deacetylase inhibitor MS-275 as a topical agent for the prevention and treatment of cutaneous squamous cell carcinoma in an SKH-1 hairless mouse model.
Authors: Authors: Kalin JH, Eroglu A, Liu H, Holtzclaw WD, Leigh I, Proby CM, Fahey JW, Cole PA, Dinkova-Kostova AT.
PLoS One
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N-terminal domain of human uracil DNA glycosylase (hUNG2) promotes targeting to uracil sites adjacent to ssDNA-dsDNA junctions.
Authors: Authors: Weiser BP, Rodriguez G, Cole PA, Stivers JT.
Nucleic Acids Res
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Akt Kinase Activation Mechanisms Revealed Using Protein Semisynthesis.
Authors: Authors: Chu N, Salguero AL, Liu AZ, Chen Z, Dempsey DR, Ficarro SB, Alexander WM, Marto JA, Li Y, Amzel LM, Gabelli SB, Cole PA.
Cell
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Hydrazide Mimics for Protein Lysine Acylation To Assess Nucleosome Dynamics and Deubiquitinase Action.
Authors: Authors: Bhat S, Hwang Y, Gibson MD, Morgan MT, Taverna SD, Zhao Y, Wolberger C, Poirier MG, Cole PA.
J Am Chem Soc
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Site-Specific Protein Labeling with N-Hydroxysuccinimide-Esters and the Analysis of Ubiquitin Ligase Mechanisms.
Authors: Authors: Dempsey DR, Jiang H, Kalin JH, Chen Z, Cole PA.
J Am Chem Soc
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Time-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome.
Authors: Authors: Weinert BT, Narita T, Satpathy S, Srinivasan B, Hansen BK, Schölz C, Hamilton WB, Zucconi BE, Wang WW, Liu WR, Brickman JM, Kesicki EA, Lai A, Bromberg KD, Cole PA, Choudhary C.
Cell
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Lysine-14 acetylation of histone H3 in chromatin confers resistance to the deacetylase and demethylase activities of an epigenetic silencing complex.
Authors: Authors: Wu M, Hayward D, Kalin JH, Song Y, Schwabe JW, Cole PA.
Elife
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Author Correction: Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours.
Authors: Authors: Lasko LM, Jakob CG, Edalji RP, Qiu W, Montgomery D, Digiammarino EL, Hansen TM, Risi RM, Frey R, Manaves V, Shaw B, Algire M, Hessler P, Lam LT, Uziel T, Faivre E, Ferguson D, Buchanan FG, Martin RL, Torrent M, Chiang GG, Karukurichi K, Langston JW, Weinert BT, Choudhary C, de Vries P, Kluge AF, Patane MA, Van Drie JH, Wang C, McElligott D, Kesicki EA, Marmorstein R, Sun C, Cole PA, Rosenberg SH, Michaelides MR, Lai A, Bromberg KD.
Nature
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Analysis of Cellular Tyrosine Phosphorylation via Chemical Rescue of Conditionally Active Abl Kinase.
Authors: Authors: Wang Z, Kim MS, Martinez-Ferrando I, Koleske AJ, Pandey A, Cole PA.
Biochemistry
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Discovery of Spiro Oxazolidinediones as Selective, Orally Bioavailable Inhibitors of p300/CBP Histone Acetyltransferases.
Authors: Authors: Michaelides MR, Kluge A, Patane M, Van Drie JH, Wang C, Hansen TM, Risi RM, Mantei R, Hertel C, Karukurichi K, Nesterov A, McElligott D, de Vries P, Langston JW, Cole PA, Marmorstein R, Liu H, Lasko L, Bromberg KD, Lai A, Kesicki EA.
ACS Med Chem Lett
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