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
Deubiquitinase processing of a non-natural linkage of ubiquitinated-PTEN.
Authors: Authors: Iwase R, Maisonet IJ, Lee K, Buhrlage SJ, Cole PA.
Bioorg Chem
View full abstract on Pubmed
Converging mechanism of UM171 and KBTBD4 neomorphic cancer mutations.
Authors: Authors: Xie X, Zhang O, Yeo MJR, Lee C, Tao R, Harry SA, Payne NC, Nam E, Paul L, Li Y, Kwok HS, Jiang H, Mao H, Hadley JL, Lin H, Batts M, Gosavi PM, D'Angiolella V, Cole PA, Mazitschek R, Northcott PA, Zheng N, Liau BB.
Nature
View full abstract on Pubmed
UM171 glues asymmetric CRL3-HDAC1/2 assembly to degrade CoREST corepressors.
Authors: Authors: Yeo MJR, Zhang O, Xie X, Nam E, Payne NC, Gosavi PM, Kwok HS, Iram I, Lee C, Li J, Chen NJ, Nguyen K, Jiang H, Wang ZA, Lee K, Mao H, Harry SA, Barakat IA, Takahashi M, Waterbury AL, Barone M, Mattevi A, Carr SA, Udeshi ND, Bar-Peled L, Cole PA, Mazitschek R, Liau BB, Zheng N.
Nature
View full abstract on Pubmed
A novel DNA repair protein, N-Myc downstream regulated gene 1 (NDRG1), links stromal tumour microenvironment to chemoresistance.
Authors: Authors: Kozlova N, Cruz KA, Doh HM, Ruzette AA, Willis NA, Hong SM, Gonzalez RS, Vyas M, Selfors LM, Dreyer S, Upstill-Goddard R, Faia KL, Wenglowsky S, Close J, Beutel AK, Jutric Z, Oliphant MUJ, 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, Nørrelykke SF, Scully R, Muranen T.
bioRxiv
View full abstract on Pubmed
AANAT kinetics of CoASH-targeted electrophiles of tryptamine and related analogs.
Authors: Authors: Wandrey N, Hamilton L, Boley J, Haynes A, Redinger M, Hill M, Hagemeister M, Cole PA, Moxley MA, Thomas AA.
Bioorg Med Chem Lett
View full abstract on Pubmed
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, Ficcaro S, Marto J, Stransky S, Duke-Cohan J, Geethadevi A, Raabe E, Sidoli S, Hicks CW, Keskin DB, Wu CJ, Cole PA, Alani RM.
bioRxiv
View full abstract on Pubmed
Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation and gliomagenesis.
Authors: Authors: Liu R, Ren X, Park YE, Feng H, Sheng X, Song X, AminiTabrizi R, Shah H, Li L, Zhang Y, Abdullah KG, Dubois-Coyne S, Lin H, Cole PA, DeBerardinis RJ, McBrayer SK, Huang H, Zhao Y.
Cell Metab
View full abstract on Pubmed
Circular Engineered Sortase for Interrogating Histone H3 in Chromatin.
Authors: Authors: Whedon SD, Lee K, Wang ZA, Zahn E, Lu C, Yapa Abeywardana M, Fairall L, Nam E, DuBois-Coyne S, De Ioannes P, Sheng X, Andrei A, Lundberg E, Jiang J, Armache KJ, Zhao Y, Schwabe JWR, Wu M, Garcia BA, Cole PA.
J Am Chem Soc
View full abstract on Pubmed
Targeting lysine acetylation readers and writers.
Authors: Authors: Zhou MM, Cole PA.
Nat Rev Drug Discov
View full abstract on Pubmed
A circular engineered sortase for interrogating histone H3 in chromatin.
Authors: Authors: Whedon SD, Lee K, Wang ZA, Zahn E, Lu C, Yapa-Abeywardana M, Fairall L, Nam E, Dubois-Coyne S, Ioannes P, Sheng X, Andrei A, Lundberg E, Jiang J, Armache KJ, Zhao Y, Schwabe JWR, Wu M, Garcia BA, Cole PA.
bioRxiv
View full abstract on Pubmed