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
Paradoxical enhancement of fear extinction memory and synaptic plasticity by inhibition of the histone acetyltransferase p300.
Authors: Authors: Marek R, Coelho CM, Sullivan RK, Baker-Andresen D, Li X, Ratnu V, Dudley KJ, Meyers D, Mukherjee C, Cole PA, Sah P, Bredy TW.
J Neurosci
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Dynamic acetylation of all lysine-4 trimethylated histone H3 is evolutionarily conserved and mediated by p300/CBP.
Authors: Authors: Crump NT, Hazzalin CA, Bowers EM, Alani RM, Cole PA, Mahadevan LC.
Proc Natl Acad Sci U S A
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Structure of the Rtt109-AcCoA/Vps75 complex and implications for chaperone-mediated histone acetylation.
Authors: Authors: Tang Y, Holbert MA, Delgoshaie N, Wurtele H, Guillemette B, Meeth K, Yuan H, Drogaris P, Lee EH, Durette C, Thibault P, Verreault A, Cole PA, Marmorstein R.
Structure
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Probing the reaction coordinate of the p300/CBP histone acetyltransferase with bisubstrate analogs.
Authors: Authors: Karukurichi KR, Cole PA.
Bioorg Chem
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Drug discovery: Reader's block.
Authors: Authors: Taverna SD, Cole PA.
Nature
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Glucose and weight control in mice with a designed ghrelin O-acyltransferase inhibitor.
Authors: Authors: Barnett BP, Hwang Y, Taylor MS, Kirchner H, Pfluger PT, Bernard V, Lin YY, Bowers EM, Mukherjee C, Song WJ, Longo PA, Leahy DJ, Hussain MA, Tschöp MH, Boeke JD, Cole PA.
Science
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BCL6 repression of EP300 in human diffuse large B cell lymphoma cells provides a basis for rational combinatorial therapy.
Authors: Authors: Cerchietti LC, Hatzi K, Caldas-Lopes E, Yang SN, Figueroa ME, Morin RD, Hirst M, Mendez L, Shaknovich R, Cole PA, Bhalla K, Gascoyne RD, Marra M, Chiosis G, Melnick A.
J Clin Invest
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Discovery of entry inhibitors for HIV-1 via a new de novo protein design framework.
Authors: Authors: Bellows ML, Taylor MS, Cole PA, Shen L, Siliciano RF, Fung HK, Floudas CA.
Biophys J
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Acetylation of tau inhibits its degradation and contributes to tauopathy.
Authors: Authors: Min SW, Cho SH, Zhou Y, Schroeder S, Haroutunian V, Seeley WW, Huang EJ, Shen Y, Masliah E, Mukherjee C, Meyers D, Cole PA, Ott M, Gan L.
Neuron
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Oncogenesis by sequestration of CBP/p300 in transcriptionally inactive hyperacetylated chromatin domains.
Authors: Authors: Reynoird N, Schwartz BE, Delvecchio M, Sadoul K, Meyers D, Mukherjee C, Caron C, Kimura H, Rousseaux S, Cole PA, Panne D, French CA, Khochbin S.
EMBO J
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