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 160E

Boston, MA 02115

Publications View
Histone modification cross-talk: analytical tools and molecular mechanisms.
Authors: Authors: Jiang J, DuBois-Coyne S, Nam E, Whedon SD, Lee K, Cole PA.
Biochem J
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Cancer-associated fibroblasts regulate DNA repair in pancreatic cancer through NDRG1-mediated R-loop processing.
Authors: Authors: Kozlova N, Cruz KA, Ruzette AA, Doh HM, Willis NA, Hong SM, Gonzalez RS, Vyas M, Selfors LM, Dreyer S, Upstill-Goddard R, Faia KL, Wenglowsky S, Close J, Beutel A, Jutric Z, Oliphant MUJ, Poluben L, Thapa B, Taylor MS, Mustonen V, Mangalath P, Halbrook CJ, Grossman JE, Hwang RF, Clohessy JG, Ruskamo S, Kursula P, Petrova B, Kanarek N, Cole PA, Chang DK, Evans CL, Nørrelykke SF, Scully R, Muranen T.
Nat Cell Biol
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Genetic mutations and inhibitors of p300 and CBP.
Authors: Authors: Robaszkiewicz A, Cole PA.
Biochim Biophys Acta Rev Cancer
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Interaction of NDRG1 and MRE11 Modulates DNA Replication and Repair.
Authors: Authors: Doh HM, Kozlova N, Wang ZA, Bae H, Cole PA, Muranen T.
Cancers (Basel)
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Structural basis for the recruitment and selective phosphorylation of Akt by mTORC2.
Authors: Authors: Taylor MS, Chen M, Hancock M, Wranik M, Miller BD, O'Meara TR, Palanski BA, Ficarro SB, Groendyke BJ, Xiang Y, Kondo KT, Linde-Garelli KY, Lee MJ, Mondal D, Freund D, Congreve S, Matas K, Hennink M, Xibinaku K, Valenstein ML, van Eeuwen T, Marto JA, Sali A, Shi Y, Gray NS, Sabatini DM, Chu N, Rogala KB, Cole PA.
Science
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Histone 3 lysine 9 dimethylation by the G9a-GLP heterodimer requires intranucleosomal product reading.
Authors: Authors: Yousefi F, Simental EA, Du Y, Whedon S, Trnka MJ, Darling D, Jia S, Panning B, Cole PA, Halic M, Al-Sady B.
bioRxiv
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Biochemistry and regulation of histone lysine L-lactylation.
Authors: Authors: Sheng X, Lin H, Cole PA, Zhao Y.
Nat Rev Mol Cell Biol
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Hydantion indolinones as AANAT inhibitors.
Authors: Authors: Wandrey N, Boley J, Gómez-Galicia D, Hill M, Bach M, Gawrych S, Hagemeister M, Cole PA, Moxley MA, Thomas AA.
Bioorg Med Chem Lett
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CoREST complex inhibition alters RNA splicing to promote neoantigen expression and enhance tumor immunity.
Authors: Authors: Fisher RJ, Park K, Lee K, Pinjusic K, Vanasse A, Ennis CS, Farokh P, Ficarro SB, Marto JA, Jiang H, Nam E, Stransky S, Duke-Cohan J, Akinci MA, Geethadevi A, Raabe E, Fiszbein A, Demehri S, Sidoli S, Hicks CW, Keskin DB, Wu CJ, Cole PA, Alani RM.
JCI Insight
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DNA bendability regulates transcription factor binding to nucleosomes.
Authors: Authors: Mariani L, Liu X, Lee K, Gisselbrecht SS, Cole PA, Bulyk ML.
Nat Struct Mol Biol
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