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
Chemical rescue of a mutant protein-tyrosine kinase.
Authors: Authors: Williams DM, Wang D, Cole PA.
J Biol Chem
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Probing the catalytic mechanism of the insulin receptor kinase with a tetrafluorotyrosine-containing peptide substrate.
Authors: Authors: Ablooglu AJ, Till JH, Kim K, Parang K, Cole PA, Hubbard SR, Kohanski RA.
J Biol Chem
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Activator-dependent transcription from chromatin in vitro involving targeted histone acetylation by p300.
Authors: Authors: Kundu TK, Palhan VB, Wang Z, An W, Cole PA, Roeder RG.
Mol Cell
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p300/CBP-associated factor histone acetyltransferase processing of a peptide substrate. Kinetic analysis of the catalytic mechanism.
Authors: Authors: Lau OD, Courtney AD, Vassilev A, Marzilli LA, Cotter RJ, Nakatani Y, Cole PA.
J Biol Chem
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Tyrosine analogues as alternative substrates for protein tyrosine kinase Csk: insights into substrate selectivity and catalytic mechanism.
Authors: Authors: Kim K, Parang K, Lau OD, Cole PA.
Bioorg Med Chem
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Tethered blockers as molecular 'tape measures' for a voltage-gated K+ channel.
Authors: Authors: Blaustein RO, Cole PA, Williams C, Miller C.
Nat Struct Biol
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HATs off: selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF.
Authors: Authors: Lau OD, Kundu TK, Soccio RE, Ait-Si-Ali S, Khalil EM, Vassilev A, Wolffe AP, Nakatani Y, Roeder RG, Cole PA.
Mol Cell
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Mechanism-based inhibition of the melatonin rhythm enzyme: pharmacologic exploitation of active site functional plasticity.
Authors: Authors: Khalil EM, De Angelis J, Ishii M, Cole PA.
Proc Natl Acad Sci U S A
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Domain interactions in protein tyrosine kinase Csk.
Authors: Authors: Sondhi D, Cole PA.
Biochemistry
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Synthesis of (2S,3R)-beta-methyltyrosine catalyzed by tyrosine phenol-lyase.
Authors: Authors: Kim K, Cole PA.
Bioorg Med Chem Lett
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