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
Multifaceted regulation of Sirtuin 2 (Sirt2) Deacetylase Activity.
Authors: Authors: Abeywardana MY, Whedon SD, Lee K, Nam E, Dovarganes R, Dubois-Coyne S, Haque IA, Wang ZA, Cole PA.
J Biol Chem
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The CoREST complex is a therapeutic vulnerability in malignant peripheral nerve sheath tumors.
Authors: Authors: Soukar I, Fisher R, Bhagavatula S, Collard M, Cole PA, Alani RM.
bioRxiv
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Structural requirements for activity of Mind bomb1 in Notch signaling.
Authors: Authors: Cao R, Gozlan O, Airich A, Tveriakhina L, Zhou H, Jiang H, Cole PA, Aster JC, Klein T, Sprinzak D, Blacklow SC.
Structure
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Protein semisynthesis reveals plasticity in HECT E3 ubiquitin ligase mechanisms.
Authors: Authors: Jiang H, Miller BD, Viennet T, Kim H, Lee K, Arthanari H, Cole PA.
Nat Chem
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p300 KAT regulates SOX10 stability and function in human melanoma.
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Cancer Res Commun
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Uncoupling histone modification crosstalk by engineering lysine demethylase LSD1.
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Nat Chem Biol
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A MOZ-TIF2 leukemia mouse model displays KAT6-dependent H3K23 propionylation and overexpression of a set of active developmental genes.
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Proc Natl Acad Sci U S A
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An autoinhibitory switch of the LSD1 disordered region controls enhancer silencing.
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Mol Cell
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KBTBD4 Cancer Hotspot Mutations Drive Neomorphic Degradation of HDAC1/2 Corepressor Complexes.
Authors: Authors: Xie X, Zhang O, Yeo MJR, Lee C, Harry SA, Paul L, Li Y, Payne NC, Nam E, 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.
bioRxiv
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Asymmetric Engagement of Dimeric CRL3 KBTBD4 by the Molecular Glue UM171 Licenses Degradation of HDAC1/2 Complexes.
Authors: Authors: Yeo MJ, Zhang O, Xie X, Nam E, Payne NC, Gosavi PM, Kwok HS, Iram I, Lee C, Li J, Chen NJ, Jiang H, Wang ZA, Lee K, Mao H, Harry SA, Barakat IA, Takahashi M, Waterbury AL, Barone M, Mattevi A, Bar-Peled L, Cole PA, Mazitschek R, Liau BB, Zheng N.
bioRxiv
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