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
Site-specific introduction of an acetyl-lysine mimic into peptides and proteins by cysteine alkylation.
Authors: Authors: Huang R, Holbert MA, Tarrant MK, Curtet S, Colquhoun DR, Dancy BM, Dancy BC, Hwang Y, Tang Y, Meeth K, Marmorstein R, Cole RN, Khochbin S, Cole PA.
J Am Chem Soc
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Enhanced interrogation: emerging strategies for cell signaling inhibition.
Authors: Authors: Huang R, Martinez-Ferrando I, Cole PA.
Nat Struct Mol Biol
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Virtual ligand screening of the p300/CBP histone acetyltransferase: identification of a selective small molecule inhibitor.
Authors: Authors: Bowers EM, Yan G, Mukherjee C, Orry A, Wang L, Holbert MA, Crump NT, Hazzalin CA, Liszczak G, Yuan H, Larocca C, Saldanha SA, Abagyan R, Sun Y, Meyers DJ, Marmorstein R, Mahadevan LC, Alani RM, Cole PA.
Chem Biol
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Electrophilic tuning of the chemoprotective natural product sulforaphane.
Authors: Authors: Ahn YH, Hwang Y, Liu H, Wang XJ, Zhang Y, Stephenson KK, Boronina TN, Cole RN, Dinkova-Kostova AT, Talalay P, Cole PA.
Proc Natl Acad Sci U S A
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Butyrate greatly enhances derivation of human induced pluripotent stem cells by promoting epigenetic remodeling and the expression of pluripotency-associated genes.
Authors: Authors: Mali P, Chou BK, Yen J, Ye Z, Zou J, Dowey S, Brodsky RA, Ohm JE, Yu W, Baylin SB, Yusa K, Bradley A, Meyers DJ, Mukherjee C, Cole PA, Cheng L.
Stem Cells
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Comparative analysis of small molecules and histone substrate analogues as LSD1 lysine demethylase inhibitors.
Authors: Authors: Culhane JC, Wang D, Yen PM, Cole PA.
J Am Chem Soc
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Analysis of p300/CBP histone acetyltransferase regulation using circular permutation and semisynthesis.
Authors: Authors: Karukurichi KR, Wang L, Uzasci L, Manlandro CM, Wang Q, Cole PA.
J Am Chem Soc
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Phosphatidylinositol 3-kinase/Akt pathway targets acetylation of Smad3 through Smad3/CREB-binding protein interaction: contribution to transforming growth factor beta1-induced Epstein-Barr virus reactivation.
Authors: Authors: Oussaief L, Hippocrate A, Ramirez V, Rampanou A, Zhang W, Meyers D, Cole P, Khelifa R, Joab I.
J Biol Chem
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In vitro enzymatic characterization of near full length EGFR in activated and inhibited states.
Authors: Authors: Qiu C, Tarrant MK, Boronina T, Longo PA, Kavran JM, Cole RN, Cole PA, Leahy DJ.
Biochemistry
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Negative regulation of TSHalpha target gene by thyroid hormone involves histone acetylation and corepressor complex dissociation.
Authors: Authors: Wang D, Xia X, Liu Y, Oetting A, Walker RL, Zhu Y, Meltzer P, Cole PA, Shi YB, Yen PM.
Mol Endocrinol
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