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
Structural basis of nSH2 regulation and lipid binding in PI3Ka.
Authors: Authors: Miller MS, Schmidt-Kittler O, Bolduc DM, Brower ET, Chaves-Moreira D, Allaire M, Kinzler KW, Jennings IG, Thompson PE, Cole PA, Amzel LM, Vogelstein B, Gabelli SB.
Oncotarget
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A selective phenelzine analogue inhibitor of histone demethylase LSD1.
Authors: Authors: 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, Taverna SD, Qian J, Tackett AJ, Ratan RR, McDonald OG, Feinberg AP, Cole PA.
ACS Chem Biol
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Structure of the p300 histone acetyltransferase bound to acetyl-coenzyme A and its analogues.
Authors: Authors: Maksimoska J, Segura-Peña D, Cole PA, Marmorstein R.
Biochemistry
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An Fc domain protein-small molecule conjugate as an enhanced immunomodulator.
Authors: Authors: Chiang MJ, Holbert MA, Kalin JH, Ahn YH, Giddens J, Amin MN, Taylor MS, Collins SL, Chan-Li Y, Waickman A, Hsiao PY, Bolduc D, Leahy DJ, Horton MR, Wang LX, Powell JD, Cole PA.
J Am Chem Soc
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Control of Foxo1 gene expression by co-activator P300.
Authors: Authors: Wondisford AR, Xiong L, Chang E, Meng S, Meyers DJ, Li M, Cole PA, He L.
J Biol Chem
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Sulphoxythiocarbamates modify cysteine residues in HSP90 causing degradation of client proteins and inhibition of cancer cell proliferation.
Authors: Authors: Zhang Y, Dayalan Naidu S, Samarasinghe K, Van Hecke GC, Pheely A, Boronina TN, Cole RN, Benjamin IJ, Cole PA, Ahn YH, Dinkova-Kostova AT.
Br J Cancer
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Catalytic mechanisms and regulation of protein kinases.
Authors: Authors: Wang Z, Cole PA.
Methods Enzymol
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Tyrosine phosphorylation of mig6 reduces its inhibition of the epidermal growth factor receptor.
Authors: Authors: Wang Z, Raines LL, Hooy RM, Roberson H, Leahy DJ, Cole PA.
ACS Chem Biol
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Architectural organization of the metabolic regulatory enzyme ghrelin O-acyltransferase.
Authors: Authors: Taylor MS, Ruch TR, Hsiao PY, Hwang Y, Zhang P, Dai L, Huang CR, Berndsen CE, Kim MS, Pandey A, Wolberger C, Marmorstein R, Machamer C, Boeke JD, Cole PA.
J Biol Chem
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Acetylation of RNA polymerase II regulates growth-factor-induced gene transcription in mammalian cells.
Authors: Authors: Schröder S, Herker E, Itzen F, He D, Thomas S, Gilchrist DA, Kaehlcke K, Cho S, Pollard KS, Capra JA, Schnölzer M, Cole PA, Geyer M, Bruneau BG, Adelman K, Ott M.
Mol Cell
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