Photo of Bill Sellers, MD

Bill Sellers, MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 714-7110


wsellers@broadinstitute.org

Photo of Bill Sellers, MD

Dana-Farber Cancer Institute
Phone: (617) 714-7110


wsellers@broadinstitute.org

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Bill Sellers, MD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Professor, Medicine, Harvard Medical School
  • Professor, Medical Oncology, Dana-Farber Cancer Institute
  • Director, Cancer Program, Broad Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

My lab studies the link between cancer dependencies identified through functional genomic and other approaches to the development of new therapeutics for cancer. My experience in overseeing work directed at understanding the genetic basis of cancer (e.g. co-discovery of EGFR mutations in lung cancer), understanding the molecular function of oncogenic and tumor suppressor pathways (e.g. PTEN and RB), and in leading drug discovery efforts at Novartis provides me with a unique background for overseeing projects in this arena. Most recently, I conceptualized and led the Cancer Cell Line Encyclopedia collaborative project between Novartis and the Broad Institute and as part of this oversaw Project DRIVE – a comprehensive assessment of gene dependency in 392 cancer cell lines. From this work, my group was among the first to discover the role of PRMT5 as a synthetic lethal interaction with the co-deletion of MTAP. Our new lab situated at the Broad Institute is currently focused on understanding the role of PRMT5 in cancer, deploying second-generation CRISPR approaches to identify new cancer dependencies and studying the role of propeller domain proteins in human cancer. At the Broad we are immersed in a highly collaborative environment replete with expert platforms that enable experimentation in these areas across a breadth of technologies.

Publications from Harvard Catalyst Profiles

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  • Keshishian H, McDonald ER, Mundt F, Melanson R, Krug K, Porter DA, Wallace L, Forestier D, Rabasha B, Marlow SE, Jane-Valbuena J, Todres E, Specht H, Robinson ML, Jean Beltran PM, Babur O, Olive ME, Golji J, Kuhn E, Burgess M, MacMullan MA, Rejtar T, Wang K, Mani DR, Satpathy S, Gillette MA, Sellers WR, Carr SA. A highly multiplexed quantitative phosphosite assay for biology and preclinical studies. Mol Syst Biol 2021; 17:e10156. PubMed
  • McKinney DC, McMillan BJ, Ranaghan MJ, Moroco JA, Brousseau M, Mullin-Bernstein Z, O'Keefe M, McCarren P, Mesleh MF, Mulvaney KM, Robinson F, Singh R, Bajrami B, Wagner FF, Hilgraf R, Drysdale MJ, Campbell AJ, Skepner A, Timm DE, Porter D, Kaushik VK, Sellers WR, Ianari A. Discovery of a First-in-Class Inhibitor of the PRMT5-Substrate Adaptor Interaction. J Med Chem 2021; 64:11148-11168. PubMed
  • Mulvaney KM, Blomquist C, Acharya N, Li R, Ranaghan MJ, O'Keefe M, Rodriguez DJ, Young MJ, Kesar D, Pal D, Stokes M, Nelson AJ, Jain SS, Yang A, Mullin-Bernstein Z, Columbus J, Bozal FK, Skepner A, Raymond D, LaRussa S, McKinney DC, Freyzon Y, Baidi Y, Porter D, Aguirre AJ, Ianari A, McMillan B, Sellers WR. Molecular basis for substrate recruitment to the PRMT5 methylosome. Mol Cell 2021. PubMed
  • Wu X, Yang X, Xiong Y, Li R, Ito T, Ahmed TA, Karoulia Z, Adamopoulos C, Wang H, Wang L, Xie L, Liu J, Ueberheide B, Aaronson SA, Chen X, Buchanan SG, Sellers WR, Jin J, Poulikakos PI. Distinct CDK6 complexes determine tumor cell response to CDK4/6 inhibitors and degraders. 2021; 2:429-443. PubMed
  • Chang L, Ruiz P, Ito T, Sellers WR. Targeting pan-essential genes in cancer: challenges and opportunities. Cancer Cell 2021. PubMed
  • Palmer AC, Plana D, Gao H, Korn JM, Yang G, Green J, Zhang X, Velazquez R, McLaughlin ME, Ruddy DA, Kowal C, Goldovitz J, Bullock C, Rivera S, Rakiec DP, Elliott G, Fordjour P, Meyer R, Loo A, Kurth E, Engelman JA, Bitter H, Sellers WR, Williams JA, Sorger PK. A proof of concept for biomarker-guided targeted therapy against ovarian cancer based on patient-derived tumor xenografts. Cancer Res 2020. PubMed
  • Nusinow DP, Szpyt J, Ghandi M, Rose CM, McDonald ER, Kalocsay M, Jané-Valbuena J, Gelfand E, Schweppe DK, Jedrychowski M, Golji J, Porter DA, Rejtar T, Wang YK, Kryukov GV, Stegmeier F, Erickson BK, Garraway LA, Sellers WR, Gygi SP. Quantitative Proteomics of the Cancer Cell Line Encyclopedia. Cell 2020; 180:387-402.e16. PubMed
  • Li H, Bullock K, Gurjao C, Braun D, Shukla SA, Bossé D, Lalani AA, Gopal S, Jin C, Horak C, Wind-Rotolo M, Signoretti S, McDermott DF, Freeman GJ, Van Allen EM, Schreiber SL, Stephen Hodi F, Sellers WR, Garraway LA, Clish CB, Choueiri TK, Giannakis M. Metabolomic adaptations and correlates of survival to immune checkpoint blockade. Nat Commun 2019; 10:4346. PubMed
  • Weiss A, Adler F, Buhles A, Stamm C, Fairhurst RA, Kiffe M, Sterker D, Centeleghe M, Wartmann M, Kinyamu-Akunda J, Schadt HS, Couttet P, Wolf A, Wang Y, Barzaghi-Rinaudo P, Murakami M, Kauffmann A, Knoepfel T, Buschmann N, Leblanc C, Mah R, Furet P, Blank J, Hofmann F, Sellers WR, Graus Porta D. FGF401, a first-in-class highly selective and potent FGFR4 inhibitor for the treatment of FGF19-driven hepatocellular cancer. Mol Cancer Ther 2019. PubMed
  • Ghandi M, Huang FW, Jané-Valbuena J, Kryukov GV, Lo CC, McDonald ER, Barretina J, Gelfand ET, Bielski CM, Li H, Hu K, Andreev-Drakhlin AY, Kim J, Hess JM, Haas BJ, Aguet F, Weir BA, Rothberg MV, Paolella BR, Lawrence MS, Akbani R, Lu Y, Tiv HL, Gokhale PC, de Weck A, Mansour AA, Oh C, Shih J, Hadi K, Rosen Y, Bistline J, Venkatesan K, Reddy A, Sonkin D, Liu M, Lehar J, Korn JM, Porter DA, Jones MD, Golji J, Caponigro G, Taylor JE, Dunning CM, Creech AL, Warren AC, McFarland JM, Zamanighomi M, Kauffmann A, Stransky N, Imielinski M, Maruvka YE, Cherniack AD, Tsherniak A, Vazquez F, Jaffe JD, Lane AA, Weinstock DM, Johannessen CM, Morrissey MP, Stegmeier F, Schlegel R, Hahn WC, Getz G, Mills GB, Boehm JS, Golub TR, Garraway LA, Sellers WR. Next-generation characterization of the Cancer Cell Line Encyclopedia. Nature 2019; 569:503-508. PubMed
  • Zamanighomi M, Jain SS, Ito T, Pal D, Daley TP, Sellers WR. GEMINI: a variational Bayesian approach to identify genetic interactions from combinatorial CRISPR screens. Genome Biol 2019; 20:137. PubMed
  • Li H, Ning S, Ghandi M, Kryukov GV, Gopal S, Deik A, Souza A, Pierce K, Keskula P, Hernandez D, Ann J, Shkoza D, Apfel V, Zou Y, Vazquez F, Barretina J, Pagliarini RA, Galli GG, Root DE, Hahn WC, Tsherniak A, Giannakis M, Schreiber SL, Clish CB, Garraway LA, Sellers WR. The landscape of cancer cell line metabolism. Nat Med 2019; 25:850-860. PubMed
  • Jeay S, Ferretti S, Holzer P, Fuchs J, Chapeau EA, Wartmann M, Sterker D, Romanet V, Murakami M, Kerr G, Durand EY, Gaulis S, Cortes-Cros M, Ruetz S, Stachyra TM, Kallen J, Furet P, Würthner J, Guerreiro N, Halilovic E, Jullion A, Kauffmann A, Kuriakose E, Wiesmann M, Jensen MR, Hofmann F, Sellers WR. Dose and Schedule Determine Distinct Molecular Mechanisms Underlying the Efficacy of the p53-MDM2 Inhibitor HDM201. Cancer Res 2018; 78:6257-6267. PubMed
  • Kim S, Tiedt R, Loo A, Horn T, Delach S, Kovats S, Haas K, Engstler BS, Cao A, Pinzon-Ortiz M, Mulford I, Acker MG, Chopra R, Brain C, di Tomaso E, Sellers WR, Caponigro G. The potent and selective cyclin-dependent kinases 4 and 6 inhibitor ribociclib (LEE011) is a versatile combination partner in preclinical cancer models. 2018; 9:35226-35240. PubMed
  • Jiang P, Sellers WR, Liu XS. Big Data Approaches for Modeling Response and Resistance to Cancer Drugs. Annu Rev Biomed Data Sci 2018; 1:1-27. PubMed
  • Shao W, Mishina YM, Feng Y, Caponigro G, Cooke VG, Rivera S, Wang Y, Shen F, Korn JM, Mathews Griner LA, Nishiguchi G, Rico A, Tellew J, Haling JR, Aversa R, Polyakov V, Zang R, Hekmat-Nejad M, Amiri P, Singh M, Keen N, Dillon MP, Lees E, Ramurthy S, Sellers WR, Stuart DD. Antitumor Properties of RAF709, a Highly Selective and Potent Inhibitor of RAF Kinase Dimers, in Tumors Driven by Mutant RAS or BRAF. Cancer Res 2018; 78:1537-1548. PubMed
  • McDonald ER, de Weck A, Schlabach MR, Billy E, Mavrakis KJ, Hoffman GR, Belur D, Castelletti D, Frias E, Gampa K, Golji J, Kao I, Li L, Megel P, Perkins TA, Ramadan N, Ruddy DA, Silver SJ, Sovath S, Stump M, Weber O, Widmer R, Yu J, Yu K, Yue Y, Abramowski D, Ackley E, Barrett R, Berger J, Bernard JL, Billig R, Brachmann SM, Buxton F, Caothien R, Caushi JX, Chung FS, Cortés-Cros M, deBeaumont RS, Delaunay C, Desplat A, Duong W, Dwoske DA, Eldridge RS, Farsidjani A, Feng F, Feng J, Flemming D, Forrester W, Galli GG, Gao Z, Gauter F, Gibaja V, Haas K, Hattenberger M, Hood T, Hurov KE, Jagani Z, Jenal M, Johnson JA, Jones MD, Kapoor A, Korn J, Liu J, Liu Q, Liu S, Liu Y, Loo AT, Macchi KJ, Martin T, McAllister G, Meyer A, Mollé S, Pagliarini RA, Phadke T, Repko B, Schouwey T, Shanahan F, Shen Q, Stamm C, Stephan C, Stucke VM, Tiedt R, Varadarajan M, Venkatesan K, Vitari AC, Wallroth M, Weiler J, Zhang J, Mickanin C, Myer VE, Porter JA, Lai A, Bitter H, Lees E, Keen N, Kauffmann A, Stegmeier F, Hofmann F, Schmelzle T, Sellers WR. Project DRIVE: A Compendium of Cancer Dependencies and Synthetic Lethal Relationships Uncovered by Large-Scale, Deep RNAi Screening. Cell 2017; 170:577-592.e10. PubMed
  • Bialucha CU, Collins SD, Li X, Saxena P, Zhang X, Dürr C, Lafont B, Prieur P, Shim Y, Mosher R, Lee D, Ostrom L, Hu T, Bilic S, Rajlic IL, Capka V, Jiang W, Wagner JP, Elliott G, Veloso A, Piel JC, Flaherty MM, Mansfield KG, Meseck EK, Rubic-Schneider T, London AS, Tschantz WR, Kurz M, Nguyen D, Bourret A, Meyer MJ, Faris JE, Janatpour MJ, Chan VW, Yoder NC, Catcott KC, McShea MA, Sun X, Gao H, Williams J, Hofmann F, Engelman JA, Ettenberg SA, Sellers WR, Lees E. Discovery and Optimization of HKT288, a Cadherin-6-Targeting ADC for the Treatment of Ovarian and Renal Cancers. 2017; 7:1030-1045. PubMed
  • Wang HQ, Halilovic E, Li X, Liang J, Cao Y, Rakiec DP, Ruddy DA, Jeay S, Wuerthner JU, Timple N, Kasibhatla S, Li N, Williams JA, Sellers WR, Huang A, Li F. Combined ALK and MDM2 inhibition increases antitumor activity and overcomes resistance in human mutant neuroblastoma cell lines and xenograft models. Elife 2017. PubMed
  • Mavrakis KJ, McDonald ER, Schlabach MR, Billy E, Hoffman GR, deWeck A, Ruddy DA, Venkatesan K, Yu J, McAllister G, Stump M, deBeaumont R, Ho S, Yue Y, Liu Y, Yan-Neale Y, Yang G, Lin F, Yin H, Gao H, Kipp DR, Zhao S, McNamara JT, Sprague ER, Zheng B, Lin Y, Cho YS, Gu J, Crawford K, Ciccone D, Vitari AC, Lai A, Capka V, Hurov K, Porter JA, Tallarico J, Mickanin C, Lees E, Pagliarini R, Keen N, Schmelzle T, Hofmann F, Stegmeier F, Sellers WR. Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5. Science 2016; 351:1208-13. PubMed
  • Munoz DM, Cassiani PJ, Li L, Billy E, Korn JM, Jones MD, Golji J, Ruddy DA, Yu K, McAllister G, DeWeck A, Abramowski D, Wan J, Shirley MD, Neshat SY, Rakiec D, de Beaumont R, Weber O, Kauffmann A, McDonald ER, Keen N, Hofmann F, Sellers WR, Schmelzle T, Stegmeier F, Schlabach MR. CRISPR Screens Provide a Comprehensive Assessment of Cancer Vulnerabilities but Generate False-Positive Hits for Highly Amplified Genomic Regions. 2016; 6:900-13. PubMed
  • Mounir Z, Korn JM, Westerling T, Lin F, Kirby CA, Schirle M, McAllister G, Hoffman G, Ramadan N, Hartung A, Feng Y, Kipp DR, Quinn C, Fodor M, Baird J, Schoumacher M, Meyer R, Deeds J, Buchwalter G, Stams T, Keen N, Sellers WR, Brown M, Pagliarini RA. ERG signaling in prostate cancer is driven through PRMT5-dependent methylation of the Androgen Receptor. Elife 2016. PubMed
  • Chen YN, LaMarche MJ, Chan HM, Fekkes P, Garcia-Fortanet J, Acker MG, Antonakos B, Chen CH, Chen Z, Cooke VG, Dobson JR, Deng Z, Fei F, Firestone B, Fodor M, Fridrich C, Gao H, Grunenfelder D, Hao HX, Jacob J, Ho S, Hsiao K, Kang ZB, Karki R, Kato M, Larrow J, La Bonte LR, Lenoir F, Liu G, Liu S, Majumdar D, Meyer MJ, Palermo M, Perez L, Pu M, Price E, Quinn C, Shakya S, Shultz MD, Slisz J, Venkatesan K, Wang P, Warmuth M, Williams S, Yang G, Yuan J, Zhang JH, Zhu P, Ramsey T, Keen NJ, Sellers WR, Stams T, Fortin PD. Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases. Nature 2016; 535:148-52. PubMed
  • Gao H, Korn JM, Ferretti S, Monahan JE, Wang Y, Singh M, Zhang C, Schnell C, Yang G, Zhang Y, Balbin OA, Barbe S, Cai H, Casey F, Chatterjee S, Chiang DY, Chuai S, Cogan SM, Collins SD, Dammassa E, Ebel N, Embry M, Green J, Kauffmann A, Kowal C, Leary RJ, Lehar J, Liang Y, Loo A, Lorenzana E, Robert McDonald E, McLaughlin ME, Merkin J, Meyer R, Naylor TL, Patawaran M, Reddy A, Röelli C, Ruddy DA, Salangsang F, Santacroce F, Singh AP, Tang Y, Tinetto W, Tobler S, Velazquez R, Venkatesan K, Von Arx F, Wang HQ, Wang Z, Wiesmann M, Wyss D, Xu F, Bitter H, Atadja P, Lees E, Hofmann F, Li E, Keen N, Cozens R, Jensen MR, Pryer NK, Williams JA, Sellers WR. High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response. Nat Med 2015; 21:1318-25. PubMed
  • Jeay S, Gaulis S, Ferretti S, Bitter H, Ito M, Valat T, Murakami M, Ruetz S, Guthy DA, Rynn C, Jensen MR, Wiesmann M, Kallen J, Furet P, Gessier F, Holzer P, Masuya K, Würthner J, Halilovic E, Hofmann F, Sellers WR, Graus Porta D. A distinct p53 target gene set predicts for response to the selective p53-HDM2 inhibitor NVP-CGM097. Elife 2015. PubMed
  • Bhang HE, Ruddy DA, Krishnamurthy Radhakrishna V, Caushi JX, Zhao R, Hims MM, Singh AP, Kao I, Rakiec D, Shaw P, Balak M, Raza A, Ackley E, Keen N, Schlabach MR, Palmer M, Leary RJ, Chiang DY, Sellers WR, Michor F, Cooke VG, Korn JM, Stegmeier F. Studying clonal dynamics in response to cancer therapy using high-complexity barcoding. Nat Med 2015; 21:440-8. PubMed
  • Fritsch C, Huang A, Chatenay-Rivauday C, Schnell C, Reddy A, Liu M, Kauffmann A, Guthy D, Erdmann D, De Pover A, Furet P, Gao H, Ferretti S, Wang Y, Trappe J, Brachmann SM, Maira SM, Wilson C, Boehm M, Garcia-Echeverria C, Chene P, Wiesmann M, Cozens R, Lehar J, Schlegel R, Caravatti G, Hofmann F, Sellers WR. Characterization of the novel and specific PI3Kα inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol Cancer Ther 2014; 13:1117-29. PubMed
  • Jaffe JD, Wang Y, Chan HM, Zhang J, Huether R, Kryukov GV, Bhang HE, Taylor JE, Hu M, Englund NP, Yan F, Wang Z, Robert McDonald E, Wei L, Ma J, Easton J, Yu Z, deBeaumount R, Gibaja V, Venkatesan K, Schlegel R, Sellers WR, Keen N, Liu J, Caponigro G, Barretina J, Cooke VG, Mullighan C, Carr SA, Downing JR, Garraway LA, Stegmeier F. Global chromatin profiling reveals NSD2 mutations in pediatric acute lymphoblastic leukemia. Nat Genet 2013; 45:1386-91. PubMed
  • Das Thakur M, Salangsang F, Landman AS, Sellers WR, Pryer NK, Levesque MP, Dummer R, McMahon M, Stuart DD. Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance. Nature 2013; 494:251-5. PubMed
  • Guagnano V, Kauffmann A, Wöhrle S, Stamm C, Ito M, Barys L, Pornon A, Yao Y, Li F, Zhang Y, Chen Z, Wilson CJ, Bordas V, Le Douget M, Gaither LA, Borawski J, Monahan JE, Venkatesan K, Brümmendorf T, Thomas DM, Garcia-Echeverria C, Hofmann F, Sellers WR, Graus-Porta D. FGFR genetic alterations predict for sensitivity to NVP-BGJ398, a selective pan-FGFR inhibitor. 2012; 2:1118-33. PubMed
  • Brachmann SM, Kleylein-Sohn J, Gaulis S, Kauffmann A, Blommers MJ, Kazic-Legueux M, Laborde L, Hattenberger M, Stauffer F, Vaxelaire J, Romanet V, Henry C, Murakami M, Guthy DA, Sterker D, Bergling S, Wilson C, Brümmendorf T, Fritsch C, Garcia-Echeverria C, Sellers WR, Hofmann F, Maira SM. Characterization of the mechanism of action of the pan class I PI3K inhibitor NVP-BKM120 across a broad range of concentrations. Mol Cancer Ther 2012; 11:1747-57. PubMed
  • Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S, Wilson CJ, Lehár J, Kryukov GV, Sonkin D, Reddy A, Liu M, Murray L, Berger MF, Monahan JE, Morais P, Meltzer J, Korejwa A, Jané-Valbuena J, Mapa FA, Thibault J, Bric-Furlong E, Raman P, Shipway A, Engels IH, Cheng J, Yu GK, Yu J, Aspesi P, de Silva M, Jagtap K, Jones MD, Wang L, Hatton C, Palescandolo E, Gupta S, Mahan S, Sougnez C, Onofrio RC, Liefeld T, MacConaill L, Winckler W, Reich M, Li N, Mesirov JP, Gabriel SB, Getz G, Ardlie K, Chan V, Myer VE, Weber BL, Porter J, Warmuth M, Finan P, Harris JL, Meyerson M, Golub TR, Morrissey MP, Sellers WR, Schlegel R, Garraway LA. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 2012; 483:603-7. PubMed
  • Maira SM, Pecchi S, Huang A, Burger M, Knapp M, Sterker D, Schnell C, Guthy D, Nagel T, Wiesmann M, Brachmann S, Fritsch C, Dorsch M, Chène P, Shoemaker K, De Pover A, Menezes D, Martiny-Baron G, Fabbro D, Wilson CJ, Schlegel R, Hofmann F, García-Echeverría C, Sellers WR, Voliva CF. Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor. Mol Cancer Ther 2012; 11:317-28. PubMed
  • Sellers WR. A blueprint for advancing genetics-based cancer therapy. Cell 2011; 147:26-31. PubMed
  • Caponigro G, Sellers WR. Advances in the preclinical testing of cancer therapeutic hypotheses. Nat Rev Drug Discov 2011; 10:179-87. PubMed
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Learn how these members are similar
Similar Members

DF/HCC members that share similar concepts* with Bill Sellers, MD but have yet to coauthor a publication with this researcher.

* Concepts are MeSH terms, automatically derived from member publications

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