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
A central role for regulated protein stability in the control of TFE3 and MITF by nutrients.
Authors: Authors: Nardone C, Palanski BA, Scott DC, Timms RT, Barber KW, Gu X, Mao A, Leng Y, Watson EV, Schulman BA, Cole PA, Elledge SJ.
Mol Cell
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KATs off: Biomedical insights from lysine acetyltransferase inhibitors.
Authors: Authors: Whedon SD, Cole PA.
Curr Opin Chem Biol
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Enzymatic Analysis of WWP2 E3 Ubiquitin Ligase Using Protein Microarrays Identifies Autophagy-Related Substrates.
Authors: Authors: Jiang H, Chiang CY, Chen Z, Nathan S, D'Agostino G, Paulo JA, Song G, Zhu H, Gabelli SB, Cole PA.
J Biol Chem
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Histone H2B Deacylation Selectivity: Exploring Chromatin's Dark Matter with an Engineered Sortase.
Authors: Authors: Wang ZA, Whedon SD, Wu M, Wang S, Brown EA, Anmangandla A, Regan L, Lee K, Du J, Hong JY, Fairall L, Kay T, Lin H, Zhao Y, Schwabe JWR, Cole PA.
J Am Chem Soc
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Multifaceted Regulation of Akt by Diverse C-Terminal Post-translational Modifications.
Authors: Authors: Salguero AL, Chen M, Balana AT, Chu N, Jiang H, Palanski BA, Bae H, Wright KM, Nathan S, Zhu H, Gabelli SB, Pratt MR, Cole PA.
ACS Chem Biol
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Site-Specific 5-Formyl Cytosine Mediated DNA-Histone Cross-Links: Synthesis and Polymerase Bypass by Human DNA Polymerase ?.
Authors: Authors: Pujari SS, Wu M, Thomforde J, Wang ZA, Chao C, Olson N, Erber L, Pomerantz WCK, Cole P, Tretyakova NY.
Angew Chem Int Ed Engl
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p300 suppresses the transition of myelodysplastic syndromes to acute myeloid leukemia.
Authors: Authors: Man N, Mas G, Karl DL, Sun J, Liu F, Yang Q, Torres-Martin M, Itonaga H, Martinez C, Chen S, Xu Y, Duffort S, Hamard PJ, Chen C, Zucconi BE, Cimmino L, Yang FC, Xu M, Cole PA, Figueroa ME, Nimer SD.
JCI Insight
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Epigenetic Silencing of BMP6 by the SIN3A-HDAC1/2 Repressor Complex Drives Melanoma Metastasis via FAM83G/PAWS1.
Authors: Authors: Min D, Byun J, Lee EJ, Khan AA, Liu C, Loudig O, Hu W, Zhao Y, Herlyn M, Tycko B, Cole PA, Ryu B.
Mol Cancer Res
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The structural basis of PTEN regulation by multi-site phosphorylation.
Authors: Authors: Dempsey DR, Viennet T, Iwase R, Park E, Henriquez S, Chen Z, Jeliazkov JR, Palanski BA, Phan KL, Coote P, Gray JJ, Eck MJ, Gabelli SB, Arthanari H, Cole PA.
Nat Struct Mol Biol
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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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