Selected Publications


Rocklin GJ, Chidyausiku TM, Goreshnik I, Ford A, Houliston S, Lemak A, Carter L, Ravichandran R, Mulligan VK, Chevalier A, Arrowsmith CH, Baker D. Global analysis of protein folding using massively parallel design, synthesis, and testing. Science 357: 168-175 (2017).

Wyatt HD, Laister RC, Martin SR, Arrowsmith CH, West SC. The SMX DNA Repair Tri-nuclease. Mol Cell 65: 848-860 (2017).

Houliston RS, Lemak A, Iqbal A, Ivanochko D, Duan S, Kaustov L, Ong MS, Fan L, Senisterra G, Brown PJ, Wang YX, Arrowsmith CH. Conformational dynamics of the TTD-PHD histone reader module of the UHRF1 epigenetic regulator reveals multiple histone-binding states, allosteric regulation, and druggability. J Biol Chem 292: 20947-20959 (2017).

He Y, Selvaraju S, Curtin ML, Jakob CG, Zhu H, Comess KM, Shaw B, The J, Lima-Fernandes E, Szewczyk MM, Cheng D, Klinge KL, Li HQ, Pliushchev M, Algire MA, Maag D, Guo J, Dietrich J, Panchal SC, Petros AM, Sweis RF, Torrent M, Bigelow LJ, Senisterra G, Li F, Kennedy S, Wu Q, Osterling DJ, Lindley DJ, Gao W, Galasinski S, Barsyte-Lovejoy D, Vedadi M, Buchanan FG, Arrowsmith CH, Chiang GG, Sun C, Pappano WN. The EED protein-protein interaction inhibitor A-395 inactivates the PRC2 complex. Nat Chem Biol 13: 389-395 (2017).

Schapira M, Tyers M, Torrent M, Arrowsmith CH. W40 repeat domain proteins; a novel target class? Nat Rev Drug Discov 16: 773-786 (2017).

Stuckey JI, Dickson BM, Cheng N, Liu Y, Norris JL, Cholensky SH, Tempel W, Qin S, Huber KG, Sagum C, Black K, Li F, Huang XP, Roth BL, Baughman BM, Senisterra G, Pattenden SG, Vedadi M, Brown PJ, Bedford MT, Min J, Arrowsmith CH, James LI, Frye SV. A cellular chemical probe targeting the chromodomains of Polycomb repressive complex 1. Nat Chem Biol 12: 180-187 (2016).

Zhu J, Sammons MA, Donahue G, Dou Z, Vedadi M, Getlik M, Barsyte-Lovejoy D, Al-awar R, Katona BW, Shilatifard A, Huang J, Hua X, Arrowsmith CH, Berger SL. Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth. Nature 525: 206-211 (2015).

Grebien F, Vedadi M, Getlik M, Giambruno R, Grover A, Avellino R, Skucha A, Vittori S, Kuznetsova E, Smil D, Barsyte-Lovejoy D, Li F, Poda G, Schapira M, Wu H, Dong A, Senisterra G, Stukalov A, Huber KV, Schönegger A, Marcellus R, Bilban M, Bock C, Brown PJ, Zuber J, Bennett KL, Al-Awar R, Delwel R, Nerlov C, Arrowsmith CH, Superti-Furga G. Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia. Nat Chem Biol 11: 571-578 (2015).

Edwards AM, Arrowsmith CH, Bountra C, Bunnage ME, Feldmann M, Knight JC, Patel DD, Prinos P, Taylor MD, Sundström M, ; SGC Open Source Target-Discovery Partnership Preclinical target validation using patient-derived cells. Nat Rev Drug Discov 14: 149-150 (2015).

Tardat M, Albert M, Kunzmann R, Liu Z, Kaustov L, Thierry R, Duan S, Brykczynska U, Arrowsmith CH, Peters AH. Cbx2 Targets PRC1 to Constitutive Heterochromatin in Mouse Zygotes in a Parent-of-Origin-Dependent Manner. Mol Cell 58: 157-171 (2015).

Shah MA, Denton EL, Arrowsmith CH, Lupien M, Schapira M. A global assessment of cancer genomic alterations in epigenetic mechanisms. Epigenetics Chromatin 7: 29 (2014).

Barsyte-Lovejoy D, Li F, Oudhoff MJ, Tatlock JH, Dong A, Zeng H, Wu H, Freeman SA, Schapira M, Senisterra GA, Kuznetsova E, Marcellus R, Allali-Hassani A, Kennedy S, Lambert JP, Couzens AL, Aman A, Gingras AC, Al-Awar R, Fish PV, Gerstenberger BS, Roberts L, Benn CL, Grimley RL, Braam MJ, Rossi FM, Sudol M, Brown PJ, Bunnage ME, Owen DR, Zaph C, Vedadi M, Arrowsmith CH. (R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells. Proc Natl Acad Sci USA 111: 12853-12858 (2014).

Gelato KA, Tauber M, Ong MS, Winter S, Hiragami-Hamada K, Sindlinger J, Lemak A, Bultsma Y, Houliston S, Schwarzer D, Divecha N, Arrowsmith CH, Fischle W. Accessibility of different histone H3-binding domains of UHRF1 is allosterically regulated by phosphatidylinositol 5-phosphate. Mol Cell 54: 905-19 (2014).

Lemak A, Wu B, Yee A, Houliston S, Lee HW, Gutmanas A, Fang X, Garcia M, Semesi A, Wang YX, Prestegard JH, Arrowsmith CH. Structural characterization of a flexible two-domain protein in solution using small angle X-ray scattering and NMR data. Structure 22:1862-1874 (2014).

Senisterra G, Wu H, Allali-Hassani A, Wasney GA, Barsyte-Lovejoy D, Dombrovski L, Dong A, Nguyen KT, Smil D, Bolshan Y, Hajian T, He H, Seitova A, Chau I, Li F, Poda G, Couture JF, Brown PJ, Al-Awar R, Schapira M, Arrowsmith CH, Vedadi M.Small molecule inhibition of MLL activity by disruption of its interaction with WDR5. Biochem J 449: 151-159 (2013)

James LI, Barsyte-Lovejoy D, Zhong N, Krichevsky L, Korboukh VK, Herold JM, MacNevin CJ, Norris JL, Sagum CA, Tempel W, Marcon E, Guo H, Gao C, Huang XP, Duan S, Emili A, Greenblatt JF, Kireev DB, Jin J, Janzen WP, Brown PJ, Bedford MT, Arrowsmith CH, Frye SV.  Discovery of a chemical probe for the L3MBTL3 methyllysine reader domain. Nat Chem Biol 9: 184-91 (2013).

Rothbart SB, Krajewski K, Nady N, Tempel W, Xue S, Badeaux AI, Barsyte-Lovejoy D, Martinez JY, Bedford MT, Fuchs SM, Arrowsmith CH, Strahl BD. Association of UHRF1 with H3K9 methylation directs the maintenance of DNA methylation. Nat Struct Mol Biol 19: 1155-60 (2012).

Nady N, Krichevsky L, Zhong N, Duan S, Tempel W, Amaya MF, Ravichandran M, Arrowsmith CH. Histone recognition by human malignant brain tumor domains. J Mol Biol 423: 702-18 (2012).

Yu W, Chory EJ, Wernimont AK, Tempel W, Scopton A, Federation A, Marineau JJ, Qi J, Barsyte-Lovejoy D, Yi J, Marcellus R, Iacob RE, Engen JR, Griffin C, Aman A, Wienholds E, Li F, Pineda J, Estiu G, Shatseva T, Hajian T, Al-Awar R, Dick JE, Vedadi M, Brown PJ, Arrowsmith CH, Bradner JE, Schapira M. Catalytic site remodeling of the DOT1L methyltransferase by selective inhibitors Nat Commun 3: 1288 (2012)

Kaustov L, Ouyang H, Amaya M, Lemak A, Nady N, Duan S, Wasney GA, Li Z, Vedadi M, Schapira M, Min J, Arrowsmith CH. Recognition and specificity determinants of the human Cbx chromodomains. J Biol Chem 286: 521-9 (2011).

Lemak A, Gutmanas A, Chitayat S, Karra M, Farès C, Sunnerhagen M, Arrowsmith CH. A novel strategy for NMR resonance assignment and protein structure determination. J Biomol NMR 49: 27-38 (2011).

Nady N, Lemak A, Walker JR, Avvakumov GV, Kareta MS, Achour M, Xue S, Duan S, Allali-Hassani A, Zuo X, Wang YX, Bronner C, Chédin F, Arrowsmith CH, Dhe-Paganon S. Recognition of Multivalent Histone States Associated with Heterochromatin by UHRF1 Protein. J Biol Chem 286: 24300-24311 (2011).

Vedadi M, Barsyte-Lovejoy D, Liu F, Rival-Gervier S, Allali-Hassani A, Labrie V, Wigle TJ, Dimaggio PA, Wasney GA, Siarheyeva A, Dong A, Tempel W, Wang SC, Chen X, Chau I, Mangano TJ, Huang XP, Simpson CD, Pattenden SG, Norris JL, Kireev DB, Tripathy A, Edwards A, Roth BL, Janzen WP, Garcia BA, Petronis A, Ellis J, Brown PJ, Frye SV, Arrowsmith CH, Jin J. A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nat Chem Biol 7: 566 (2011).

Schuetz A, Min J, Allali-Hassani A, Schapira M, Shuen M, Loppnau P, Mazitschek R, Kwiatkowski NP, Lewis TA, Maglathin RL, McLean TH, Bochkarev A, Plotnikov AN, Vedadi M, Arrowsmith CH. Human HDAC7 harbors a class IIa histone deacetylase-specific zinc binding motif and cryptic deacetylase activity. J Biol Chem 283: 11355-11363 (2008).

Nady N, Min J, Kareta MS, Chédin F, Arrowsmith CH. A SPOT on the chromatin landscape? Histone peptide arrays as a tool for epigenetic research. Trends Biochem Sci 33: 305-313 (2008).

Sheng Y, Laister RC, Lemak A, Wu B, Tai E, Duan S, Lukin J, Sunnerhagen M, Srisailam S, Karra M, Benchimol S, Arrowsmith CH. Molecular Basis of Pirh2-mediated p53 ubiquitylation. Nat Struct Mol Biol 15: 1334-1342 (2008).

Avvakumov GV, Walker JR, Xue S, Li Y, Duan S, Bronner C, Arrowsmith CH, Dhe-Paganon S. Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1. Nature 455: 822-825 (2008).

Min J, Allali-Hassani A, Nady N, Qi C, Ouyang H, Liu Y, MacKenzie F, Vedadi M, Arrowsmith CH. L3MBTL1 recognition of mono- and dimethylated histones. Nat Struct Mol Biol 14: 1229-1230 (2007).

Sheng Y, Saridakis V, Sarkari F, Duan S, Wu T, Arrowsmith CH, Frappier L. Molecular recognition of p53 and MDM2 by USP7/HAUSP. Nat Struct Mol Biol. 13: 285-291 (2006).

Schuetz A, Allali-Hassani A, Martín F, Loppnau P, Vedadi M, Bochkarev A, Plotnikov AN, Arrowsmith CH, Min J. Structural basis for molecular recognition and presentation of histone H3 By WDR5. EMBO J 25: 4245-4252 (2006).

Saridakis V, Sheng Y, Sarkari F, Holowaty MN, Shire K, Nguyen T, Zhang RG, Liao J, Lee W, Edwards AM, Arrowsmith CH, Frappier L. Structure of the p53 binding domain of HAUSP/USP7 bound to Epstein-Barr nuclear antigen 1 implications for EBV-mediated immortalization. Mol Cell 18: 25-36 (2005).

Bochkareva E, Kaustov L, Ayed A, Yi GS, Lu Y, Pineda-Lucena A, Liao JC, Okorokov AL, Milner J, Arrowsmith CH, Bochkarev A. Single-stranded DNA mimicry in the p53 transactivation domain interaction with replication protein A. Proc Natl Acad Sci USA 102: 15412-15417 (2005).

Yee A, Chang X, Pineda-Lucena A, Wu B, Semesi A, Le B, Ramelot T, Lee GM, Bhattacharyya S, Gutierrez P, Denisov A, Lee CH, Cort JR, Kozlov G, Liao J, Finak G, Chen L, Wishart D, Lee W, McIntosh LP, Gehring K, Kennedy MA, Edwards AM, Arrowsmith CH. An NMR approach to structural proteomics. Proc Natl Acad Sci USA 99: 1825-1830 (2002).

Christendat D, Yee A, Dharamsi A, Kluger Y, Savchenko A, Cort JR, Booth V, Mackereth CD, Saridakis V, Ekiel I, Kozlov G, Maxwell KL, Wu N, McIntosh LP, Gehring K, Kennedy MA, Davidson AR, Pai EF, Gerstein M, Edwards AM, Arrowsmith CH. Structural proteomics of an archeon. Nat Struct Biol 7: 903-909 (2000).