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 dissection of the effects of tyrosine phosphorylation of SHP-2.
Authors: Authors: Lu W, Shen K, Cole PA.
Biochemistry
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A role for cofactor-cofactor and cofactor-histone interactions in targeting p300, SWI/SNF and Mediator for transcription.
Authors: Authors: Huang ZQ, Li J, Sachs LM, Cole PA, Wong J.
EMBO J
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Tax recruitment of CBP/p300, via the KIX domain, reveals a potent requirement for acetyltransferase activity that is chromatin dependent and histone tail independent.
Authors: Authors: Georges SA, Giebler HA, Cole PA, Luger K, Laybourn PJ, Nyborg JK.
Mol Cell Biol
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Transcriptional activation by thyroid hormone receptor-beta involves chromatin remodeling, histone acetylation, and synergistic stimulation by p300 and steroid receptor coactivators.
Authors: Authors: Lee KC, Li J, Cole PA, Wong J, Kraus WL.
Mol Endocrinol
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The role of C-terminal tyrosine phosphorylation in the regulation of SHP-1 explored via expressed protein ligation.
Authors: Authors: Zhang Z, Shen K, Lu W, Cole PA.
J Biol Chem
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Down-regulation of p300/CBP histone acetyltransferase activates a senescence checkpoint in human melanocytes.
Authors: Authors: Bandyopadhyay D, Okan NA, Bales E, Nascimento L, Cole PA, Medrano EE.
Cancer Res
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Structure of the GCN5 histone acetyltransferase bound to a bisubstrate inhibitor.
Authors: Authors: Poux AN, Cebrat M, Kim CM, Cole PA, Marmorstein R.
Proc Natl Acad Sci U S A
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Substrate conformational restriction and CD45-catalyzed dephosphorylation of tail tyrosine-phosphorylated Src protein.
Authors: Authors: Wang D, Esselman WJ, Cole PA.
J Biol Chem
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Acetylation of nucleosomal histones by p300 facilitates transcription from tax-responsive human T-cell leukemia virus type 1 chromatin template.
Authors: Authors: Lu H, Pise-Masison CA, Fletcher TM, Schiltz RL, Nagaich AK, Radonovich M, Hager G, Cole PA, Brady JN.
Mol Cell Biol
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Development of photo-crosslinking reagents for protein kinase-substrate interactions.
Authors: Authors: Parang K, Kohn JA, Saldanha SA, Cole PA.
FEBS Lett
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