Photo of Philip Cole,  MD, PhD

Philip Cole, MD, PhD

Brigham And Women's Hospital

Brigham And Women's Hospital
Phone: (617) 525-5208


pacole@bwh.harvard.edu

Philip Cole, MD, PhD

Brigham And Women's Hospital

EDUCATIONAL TITLES

  • Professor, Medicine, Harvard Medical School
  • Senior Investigator, Division of Genetics, Medicine, Brigham And Women's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

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.

Publications

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  • 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. Discovery of Spirohydantoins as Selective, Orally Bioavailable Inhibitors of p300/CBP Histone Acetyltransferases. Bioorg Med Chem Lett 2021. PubMed
  • Jiang H, Dempsey DR, Cole PA. Ubiquitin Ligase Activities of WWP1 Germline Variants K740N and N745S. Biochemistry 2021; 60:357-364. PubMed
  • Huang H, Zhang D, Weng Y, Delaney K, Tang Z, Yan C, Qi S, Peng C, Cole PA, Roeder RG, Zhao Y. The regulatory enzymes and protein substrates for the lysine β-hydroxybutyrylation pathway. Sci Adv 2021. PubMed
  • Jiang H, Cole PA. N-Terminal Protein Labeling with N-Hydroxysuccinimide Esters and Microscale Thermophoresis Measurements of Protein-Protein Interactions Using Labeled Protein. Curr Protoc 2021; 1:e14. PubMed
  • Wang ZA, Cole PA. The Chemical Biology of Reversible Lysine Post-translational Modifications. Cell Chem Biol 2020; 27:953-969. PubMed
  • Hsu JW, Bai M, Li K, Yang JS, Chu N, Cole PA, Eck MJ, Li J, Hsu VW. The protein kinase Akt acts as a coat adaptor in endocytic recycling. Nat Cell Biol 2020. PubMed
  • Wang ZA, Millard CJ, Lin CL, Gurnett JE, Wu M, Lee K, Fairall L, Schwabe JW, Cole PA. Diverse nucleosome Site-Selectivity among histone deacetylase complexes. Elife 2020. PubMed
  • Morrison-Smith CD, Knox TM, Filic I, Soroko KM, Eschle BK, Wilkens MK, Gokhale PC, Giles F, Griffin A, Brown B, Shapiro GI, Zucconi BE, Cole PA, Lemieux ME, French CA. Combined Targeting of the BRD4-NUT-p300 Axis in NUT Midline Carcinoma by Dual Selective Bromodomain Inhibitor, NEO2734. Mol Cancer Ther 2020. PubMed
  • Xiong Y, Wang L, Di Giorgio E, Akimova T, Beier UH, Han R, Trevisanut M, Kalin JH, Cole PA, Hancock WW. Inhibiting the coregulator CoREST impairs Foxp3+ Treg function and promotes antitumor immunity. J Clin Invest 2020; 130:1830-1842. PubMed
  • Song Y, Dagil L, Fairall L, Robertson N, Wu M, Ragan TJ, Savva CG, Saleh A, Morone N, Kunze MBA, Jamieson AG, Cole PA, Hansen DF, Schwabe JWR. Mechanism of Crosstalk between the LSD1 Demethylase and HDAC1 Deacetylase in the CoREST Complex. Cell Rep 2020; 30:2699-2711.e8. PubMed
  • Jiang H, D'Agostino GD, Cole PA, Dempsey DR. Selective protein N-terminal labeling with N-hydroxysuccinimide esters. Methods Enzymol 2020; 639:333-353. PubMed
  • Chu N, Viennet T, Bae H, Salguero A, Boeszoermenyi A, Arthanari H, Cole PA. The structural determinants of PH domain-mediated regulation of Akt revealed by segmental labeling. Elife 2020. PubMed
  • Anastas JN, Zee BM, Kalin JH, Kim M, Guo R, Alexandrescu S, Blanco MA, Giera S, Gillespie SM, Das J, Wu M, Nocco S, Bonal DM, Nguyen QD, Suva ML, Bernstein BE, Alani R, Golub TR, Cole PA, Filbin MG, Shi Y. Re-programing Chromatin with a Bifunctional LSD1/HDAC Inhibitor Induces Therapeutic Differentiation in DIPG. Cancer Cell 2019; 36:528-544.e10. PubMed
  • Miller SA, Policastro RA, Savant SS, Sriramkumar S, Ding N, Lu X, Mohammad HP, Cao S, Kalin JH, Cole PA, Zentner GE, O'Hagan HM. Lysine-Specific Demethylase 1 Mediates AKT Activity and Promotes Epithelial-to-Mesenchymal Transition in -Mutant Colorectal Cancer. Mol Cancer Res 2019. PubMed
  • Jiang H, Thomas SN, Chen Z, Chiang CY, Cole PA. Comparative analysis of the catalytic regulation of NEDD4-1 and WWP2 ubiquitin ligases. J Biol Chem 2019. PubMed
  • Van de Velde S, Wiater E, Tran M, Hwang Y, Cole PA, Montminy M. CREB Promotes Beta Cell Gene Expression by Targeting Its Coactivators to Tissue-Specific Enhancers. Mol Cell Biol 2019. PubMed
  • Henager SH, Henriquez S, Dempsey DR, Cole PA. Analysis of Site-Specific Phosphorylation of PTEN by Using Enzyme-Catalyzed Expressed Protein Ligation. Chembiochem 2019. PubMed
  • Kim E, Zucconi BE, Wu M, Nocco SE, Meyers DJ, McGee JS, Venkatesh S, Cohen DL, Gonzalez EC, Ryu B, Cole PA, Alani RM. MITF Expression Predicts Therapeutic Vulnerability to p300 Inhibition in Human Melanoma. Cancer Res 2019; 79:2649-2661. PubMed
  • Zucconi BE, Makofske JL, Meyers DJ, Hwang Y, Wu M, Kuroda MI, Cole PA. Combination Targeting of the Bromodomain and Acetyltransferase Active Site of p300/CBP. Biochemistry 2019; 58:2133-2143. PubMed
  • Liu Y, Bao C, Wang L, Han R, Beier UH, Akimova T, Cole PA, Dent SYR, Hancock WW. Complementary Roles of GCN5 and PCAF in Foxp3+ T-Regulatory Cells. Cancers (Basel) 2019. PubMed
  • Cole PA, Chu N, Salguero AL, Bae H. AKTivation mechanisms. Curr Opin Struct Biol 2019; 59:47-53. PubMed
  • Kalin JH, Eroglu A, Liu H, Holtzclaw WD, Leigh I, Proby CM, Fahey JW, Cole PA, Dinkova-Kostova AT. Investigation into the use of histone deacetylase inhibitor MS-275 as a topical agent for the prevention and treatment of cutaneous squamous cell carcinoma in an SKH-1 hairless mouse model. PLoS ONE 2019; 14:e0213095. PubMed
  • Chu N, Salguero AL, Liu AZ, Chen Z, Dempsey DR, Ficarro SB, Alexander WM, Marto JA, Li Y, Amzel LM, Gabelli SB, Cole PA. Akt Kinase Activation Mechanisms Revealed Using Protein Semisynthesis. Cell 2018; 174:897-907.e14. PubMed
  • Wang Z, Kim MS, Martinez-Ferrando I, Koleske AJ, Pandey A, Cole PA. Analysis of Cellular Tyrosine Phosphorylation via Chemical Rescue of Conditionally Active Abl Kinase. Biochemistry 2018; 57:1390-1398. PubMed
  • Dempsey DR, Jiang H, Kalin JH, Chen Z, Cole PA. Site-Specific Protein Labeling with N-Hydroxysuccinimide-Esters and the Analysis of Ubiquitin Ligase Mechanisms. J Am Chem Soc 2019; 140:9374-9378. PubMed
  • Dempsey DR, Cole PA. Protein Chemical Approaches to Understanding PTEN Lipid Phosphatase Regulation. Methods Enzymol 2019; 607:405-422. PubMed
  • Bhat S, Hwang Y, Gibson MD, Morgan MT, Taverna SD, Zhao Y, Wolberger C, Poirier MG, Cole PA. Hydrazide Mimics for Protein Lysine Acylation To Assess Nucleosome Dynamics and Deubiquitinase Action. J Am Chem Soc 2019; 140:9478-9485. PubMed
  • Weiser BP, Rodriguez G, Cole PA, Stivers JT. N-terminal domain of human uracil DNA glycosylase (hUNG2) promotes targeting to uracil sites adjacent to ssDNA-dsDNA junctions. Nucleic Acids Res 2019; 46:7169-7178. PubMed
  • Weinert BT, Narita T, Satpathy S, Srinivasan B, Hansen BK, Schölz C, Hamilton WB, Zucconi BE, Wang WW, Liu WR, Brickman JM, Kesicki EA, Lai A, Bromberg KD, Cole PA, Choudhary C. Time-Resolved Analysis Reveals Rapid Dynamics and Broad Scope of the CBP/p300 Acetylome. Cell 2019; 174:231-244.e12. PubMed
  • Wu M, Hayward D, Kalin JH, Song Y, Schwabe JW, Cole PA. Lysine-14 acetylation of histone H3 in chromatin confers resistance to the deacetylase and demethylase activities of an epigenetic silencing complex. Elife 2019. PubMed
  • Esadze A, Rodriguez G, Weiser BP, Cole PA, Stivers JT. Measurement of nanoscale DNA translocation by uracil DNA glycosylase in human cells. Nucleic Acids Res 2018; 45:12413-12424. PubMed
  • Boija A, Mahat DB, Zare A, Holmqvist PH, Philip P, Meyers DJ, Cole PA, Lis JT, Stenberg P, Mannervik M. CBP Regulates Recruitment and Release of Promoter-Proximal RNA Polymerase II. Mol Cell 2019; 68:491-503.e5. PubMed
  • Rodriguez G, Esadze A, Weiser BP, Schonhoft JD, Cole PA, Stivers JT. Disordered N-Terminal Domain of Human Uracil DNA Glycosylase (hUNG2) Enhances DNA Translocation. ACS Chem Biol 2018; 12:2260-2263. PubMed
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