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 screen identifies diverse and novel HDAC inhibitors as repressors of NUT function: implications for NUT carcinoma pathogenesis and treatment.
Authors: Authors: Shiota H, Alekseyenko AA, Wang ZA, Filic I, Knox TM, Luong NM, Huang Y, Scott DA, Jones KL, Gokhale PC, Lemieux ME, Cole PA, Kuroda MI, French CA.
Mol Cancer Res
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HDAC2 targeting stabilizes the CoREST complex in renal tubular cells and protects against renal ischemia/reperfusion injury.
Authors: Authors: Aufhauser DD, Hernandez P, Concors SJ, O'Brien C, Wang Z, Murken DR, Samanta A, Beier UH, Krumeich L, Bhatti TR, Wang Y, Ge G, Wang L, Cheraghlou S, Wagner FF, Holson EB, Kalin JH, Cole PA, Hancock WW, Levine MH.
Sci Rep
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Discovery of Spirohydantoins as Selective, Orally Bioavailable Inhibitors of p300/CBP Histone Acetyltransferases.
Authors: Authors: Ji Z, Clark RF, Bhat V, Matthew Hansen T, Lasko LM, Bromberg KD, Manaves V, Algire M, Martin R, Qiu W, Torrent M, Jakob CG, Liu H, Cole PA, Marmorstein R, Kesicki EA, Lai A, Michaelides MR.
Bioorg Med Chem Lett
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The regulatory enzymes and protein substrates for the lysine ß-hydroxybutyrylation pathway.
Authors: Authors: Huang H, Zhang D, Weng Y, Delaney K, Tang Z, Yan C, Qi S, Peng C, Cole PA, Roeder RG, Zhao Y.
Sci Adv
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Ubiquitin Ligase Activities of WWP1 Germline Variants K740N and N745S.
Authors: Authors: Jiang H, Dempsey DR, Cole PA.
Biochemistry
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N-Terminal Protein Labeling with N-Hydroxysuccinimide Esters and Microscale Thermophoresis Measurements of Protein-Protein Interactions Using Labeled Protein.
Authors: Authors: Jiang H, Cole PA.
Curr Protoc
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Elucidation of remdesivir cytotoxicity pathways through genome-wide CRISPR-Cas9 screening and transcriptomics.
Authors: Authors: Akinci E, Cha M, Lin L, Yeo G, Hamilton MC, Donahue CJ, Bermudez-Cabrera HC, Zanetti LC, Chen M, Barkal SA, Khowpinitchai B, Chu N, Velimirovic M, Jodhani R, Fife JD, Sovrovic M, Cole PA, Davey RA, Cassa CA, Sherwood RI.
bioRxiv
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The Structural Determinants of PH Domain-Mediated Regulation of Akt Revealed by Segmental Labeling.
Authors: Authors: Chu N, Viennet T, Bae H, Salguero A, Boeszoermenyi A, Arthanari H, Cole PA.
Elife
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The Chemical Biology of Reversible Lysine Post-translational Modifications.
Authors: Authors: Wang ZA, Cole PA.
Cell Chem Biol
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The protein kinase Akt acts as a coat adaptor in endocytic recycling.
Authors: Authors: Hsu JW, Bai M, Li K, Yang JS, Chu N, Cole PA, Eck MJ, Li J, Hsu VW.
Nat Cell Biol
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