Recent Neel Lab Publications

2023

• • Genome-wide CRISPR/Cas9 screens reveal shared and cell-specific mechanisms of resistance to SHP2 inhibition
    Wei Wei , Mitchell J. Geer, Xinyi Guo, Igor Dolgalev, Neville E. Sanjana, and Benjamin G. Neel
    J Exp Med (2023) 220 (5): e20221563. doi: 10.1084/jem.20221563

2021

• Ontogeny and Vulnerabilities of Drug-Tolerant Persisters in HER2+ Breast Cancer
  Chewei Anderson Chang, Jayu Jen, Shaowen Jiang, Azin Sayad, Arvind Singh Mer, Kevin R Brown, Allison M.L Nixon, Avantika Dhabaria, Kwan Ho Tang, David Venet, Christos Sotiriou, Jiehui Deng, Kwok-Kin Wong, Sylvia Adams, Peter Meyn, Adriana Heguy, Jane A Skok, Aristotelis Tsirigos, Beatrix Ueberheide, Jason Moffat, Abhyudai Singh, Benjamin Haibe-Kains, Alireza Khodadadi-Jamayran and Benjamin G Neel
  Cancer Discov. OnlineFirst version published on December 15, 2021. doi: 10.1158/2159-8290.CD-20-1265
• Combined Inhibition of SHP2 and CXCR1/2 Promotes Anti-Tumor T Cell Response in NSCLC.
  Tang KH, Li S, Khodadadi-Jamayran A, Jen J, Han H, Guidry K, Chen T, Hao Y, Fedele C, Zebala JA, Maeda DY, Christensen JG, Olson P, Athanas A, Loomis CA, Tsirigos A, Wong KK, Neel BG.
  Cancer Discov. 2021 Aug 5:candisc.0369.2021. doi: 10.1158/2159-8290.CD-21-0369. Online ahead of print.
  PMID: 34353854
• Computational modeling of ovarian cancer dynamics suggests optimal strategies for therapy and screening.
  Shengqing Gu, Stephanie Lheureux, Azin Sayada, Paulina Cybulska, Liat Hogen, Iryna Vyarvelska, Dongsheng Tu, Wendy R. Parulekar, Matthew Nankivell, Sean Kehoe, Dennis S. Chi, Douglas A. Levine, Marcus Q. Bernardini, Barry Rosen, Amit Oza, Myles Brown, and Benjamin G. Neel
  PNAS June 22, 2021 118 (25) e2026663118; https://doi.org/10.1073/pnas.2026663118 [Contributed by Myles Brown, May 7, 2021]
• Genetically Defined, Syngeneic Organoid Platform for Developing Combination Therapies for Ovarian Cancer
  Zhang S, Iyer S, Ran H, Dolgalev I, Gu S, Wei W, Foster CJR, Loomis CA, Olvera N, Dao F, Levine DA, Weinberg RA, Neel BG.
  Cancer Discov. 2021 Feb;11(2):362-383. doi: 10.1158/2159-8290.CD-20-0455. Epub 2020 Nov 6.
  PMID: 33158842
• Genetically Defined Syngeneic Mouse Models of Ovarian Cancer as Tools for the Discovery of Combination Immunotherapy.
  Iyer S, Zhang S, Yucel S, Horn H, Smith SG, Reinhardt F, Hoefsmit E, Assatova B, Casado J, Meinsohn MC, Barrasa MI, Bell GW, Pérez-Villatoro F, Huhtinen K, Hynninen J, Oikkonen J, Galhenage PM, Pathania S, Hammond PT, Neel BG, Farkkila A, Pépin D, Weinberg RA.
  Cancer Discov. 2021 Feb;11(2):384-407. doi: 10.1158/2159-8290.CD-20-0818. Epub 2020 Nov 6.
  PMID: 33158843
• SHP2 inhibition diminishes KRASG12C cycling and promotes tumor microenvironment remodeling
  Carmine Fedele, Shuai Li, Kai Wen Teng, Connor Foster, David Peng, Hao Ran, Paolo Mita, Mitchell Geer, Takamitsu Hattori, Akiko Koide, Yubao Wang, Kwan H. Tang, Joshua Leinwand, Wei Wang, Brian Diskin, Jiehui Deng, Ting Chen, Igor Dolgalev, Ugur Ozerdem, George Miller, Shohei Koide, Kwok-Kin Wong, Benjamin G. Neel
  J Exp Med (2021) 218 (1): e20201414.
  https://doi.org/10.1084/jem.20201414 [preprint posted on bioRxiv 2020 May 31]
• Distinct fibroblast functional states drive clinical outcomes in ovarian cancer and are regulated by TCF21.
  Hussain A, Voisin V, Poon S, Karamboulas C, Bui NHB, Meens J, Dmytryshyn J, Ho VW, Tang KH, Paterson J, Clarke BA, Bernardini MQ, Bader GD, Neel BG, Ailles LE.
  J Exp Med. 2020 Aug 3;217(8):e20191094. doi: 10.1084/jem.20191094.
  PMID: 32434219
• Moyamoya Disease-Associated RNF213 Alleles Encode Dominant Negative Alleles That Globally Impair Ubiquitylation
  Abhishek Bhardwaj, Robert S. Banh, Wei Zhang, Sachdev S. Sidhu, Benjamin G. Neel
  doi: https://doi.org/10.1101/2020.05.24.113795 [preprint posted on bioRxiv 2020 May 26]

2019

• Both fallopian tube and ovarian surface epithelium are cells-of-origin for high-grade serous ovarian carcinoma.
  Shuang Zhang, Igor Dolgalev, Tao Zhang, Hao Ran, Douglas A. Levine, Benjamin G. Neel
  Nat Commun 10, 5367 (2019) doi:10.1038/s41467-019-13116-2 [preprint posted on bioRxiv 2018 Nov 29]
• The Gp1ba-Cre transgenic mouse: a new model to delineate platelet and leukocyte functions.
  Nagy Z, Vögtle T, Geer MJ, Mori J, Heising S, Di Nunzio G, Gareus R, Tarakhovsky A, Weiss A, Neel BG, Desanti GE, Mazharian A, Senis YA.
  Blood. 2019 Jan 24;133(4):331-343. doi: 10.1182/blood-2018-09-877787. Epub 2018 Nov 14. PMID: 30429161
• Computational Modeling of Ovarian Cancer Reveals Optimal Strategies for Therapy and Screening
  Shengqing S Gu, Stephanie Lheureux, Azin Sayad, Paulina Cybulska, Liat Ben-David Hogen, Iryna Vyarvelska, Dongsheng Tu, Wendy Parulekar, Douglas A Levine, Marcus Q Bernardini, Barry Rosen, Amit Oza, Benjamin G Neel
  doi: https://doi.org/10.1101/19009712 [preprint posted on MedRxiv 2019 Oct 18]
• N-Glycoproteomics of Patient-Derived Xenografts: A Strategy to Discover Tumor-Associated Proteins in High-Grade Serous Ovarian Cancer.
  Sinha A, Hussain A, Ignatchenko V, Ignatchenko A, Tang KH, Ho VWH, Neel BG, Clarke B, Bernardini MQ, Ailles L, Kislinger T.
  Cell Syst. 2019 Apr 24;8(4):345-351.e4. doi: 10.1016/j.cels.2019.03.011. Epub 2019 Apr 10. PMID: 30981729
• An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity.
  Kopper O, de Witte CJ, Lõhmussaar K, Valle-Inclan JE, Hami N, Kester L, Balgobind AV, Korving J, Proost N, Begthel H, van Wijk LM, Revilla SA, Theeuwsen R, van de Ven M, van Roosmalen MJ, Ponsioen B, Ho VWH, Neel BG, Bosse T, Gaarenstroom KN, Vrieling H, Vreeswijk MPG, van Diest PJ, Witteveen PO, Jonges T, Bos JL, van Oudenaarden A, Zweemer RP, Snippert HJG, Kloosterman WP, Clevers H.
  Nat Med. 2019 May;25(5):838-849. doi: 10.1038/s41591-019-0422-6. Epub 2019 Apr 22.
  PMID: 31011202
• The Noonan Syndrome-linked Raf1L613V mutation drives increased glial number in the mouse cortex and enhanced learning.
  Holter MC, Hewitt LT, Koebele SV, Judd JM, Xing L, Bimonte-Nelson HA, Conrad CD, Araki T, Neel BG, Snider WD, Newbern JM.
  PLoS Genet. 2019 Apr 24;15(4):e1008108. doi: 10.1371/journal.pgen.1008108. eCollection 2019 Apr. PMID: 31017896
• Phase I study of local radiation and tremelimumab in patients with inoperable locally recurrent or metastatic breast cancer.
  Jiang DM, Fyles A, Nguyen LT, Neel BG, Sacher A, Rottapel R, Wang BX, Ohashi PS, Sridhar SS.
  Oncotarget. 2019 Apr 26;10(31):2947-2958. doi: 10.18632/oncotarget.26893. eCollection 2019 Apr 26.
  PMID: 31105877
• Migration rather than proliferation transcriptomic signatures are strongly associated with breast cancer patient survival.
  Nair NU, Das A, Rogkoti VM, Fokkelman M, Marcotte R, de Jong CG, Koedoot E, Lee JS, Meilijson I, Hannenhalli S, Neel BG, de Water BV, Le Dévédec SE, Ruppin E.
  Sci Rep. 2019 Jul 29;9(1):10989. doi: 10.1038/s41598-019-47440-w.
  PMID: 31358840
• Activated Thiol Sepharose-based proteomic approach to quantify reversible protein oxidation.
  Xu Y, Andrade J, Ueberheide B, Neel BG.
  FASEB J. 2019 Nov;33(11):12336-12347. doi: 10.1096/fj.201900693R. Epub 2019 Aug 26. PMID: 31451050
• Catalytic dysregulation of SHP2 leading to Noonan syndromes impacts on platelet signaling and functions.
  Bellio M, Garcia C, Edouard T, Voisin S, Neel BG, Cabou C, Valet P, Mori J, Mazharian A, Senis YA, Yart A, Payrastre B, Severin S.
  Blood. 2019 Sep 27. pii: blood.2019001543. doi: 10.1182/blood.2019001543. [Epub ahead of print] PMID: 31562133

2018

• Both Fallopian Tube and Ovarian Surface Epithelium Can Act as Cell-of-Origin for High Grade Serous Ovarian Carcinoma
  Benjamin G Neel, Shuang Zhang, Tao Zhang, Igor Dolgalev, Hao Ran, Douglas A Levine
  bioRxiv 481200; doi: https://doi.org/10.1101/481200 [preprint posted on bioRxiv]
• The Gp1ba-Cre transgenic mouse: a new model to delineate platelet and leukocyte functions.
  Nagy Z, Vögtle T, Geer MJ, Mori J, Heising S, Di Nunzio G, Gareus R, Tarakhovsky A, Weiss A, Neel BG, Desanti GE, Mazharian A, Senis YA.
  Blood. 2018 Nov 14. pii: blood-2018-09-877787. doi: 10.1182/blood-2018-09-877787. [Epub ahead of print]

  PMID: 30429161

• Pathological Oxidation of PTPN12 Underlies ABL1 Phosphorylation in Hereditary Leiomyomatosis and Renal Cell Carcinoma.
  Xu Y, Taylor P, Andrade J, Ueberheide B, Shuch B, Glazer PM, Bindra RS, Moran MF, Linehan WM, Neel BG.
  Cancer Res. 2018 Oct 8. pii: canres.0901.2018. doi: 10.1158/0008-5472.CAN-18-0901. [Epub ahead of print]

  PMID: 30297534

• Off-target inhibition by active site-targeting SHP2 inhibitors.
  Tsutsumi R, Ran H, Neel BG.
  FEBS Open Bio. 2018 Aug 1;8(9):1405-1411. doi: 10.1002/2211-5463.12493. eCollection 2018 Sep.

  PMID: 30186742 Free PMC Article

• SHP2 Inhibition Prevents Adaptive Resistance to MEK Inhibitors in Multiple Cancer Models.
  Fedele C, Ran H, Diskin B, Wei W, Jen J, Geer MJ, Araki K, Ozerdem U, Simeone DM, Miller G, Neel BG, Tang KH.
  Cancer Discov. 2018 Oct;8(10):1237-1249. doi: 10.1158/2159-8290.CD-18-0444. Epub 2018 Jul 25.

  PMID: 30045908

• Vitamin C in Stem Cell Reprogramming and Cancer.
  Cimmino L, Neel BG, Aifantis I.
  Trends Cell Biol. 2018 Sep;28(9):698-708. doi: 10.1016/j.tcb.2018.04.001. Epub 2018 Apr 30. Review.

  PMID: 29724526

• Noonan syndrome-causing SHP2 mutants impair ERK-dependent chondrocyte differentiation during endochondral bone growth.
  Tajan M, Pernin-Grandjean J, Beton N, Gennero I, Capilla F, Neel BG, Araki T, Valet P, Tauber M, Salles JP, Yart A, Edouard T.
  Hum Mol Genet. 2018 Jul 1;27(13):2276-2289. doi: 10.1093/hmg/ddy133.

  PMID: 29659837

• SHP2 regulates skeletal cell fate by modifying SOX9 expression and transcriptional activity.
  Zuo C, Wang L, Kamalesh RM, Bowen ME, Moore DC, Dooner MS, Reginato AM, Wu Q, Schorl C, Song Y, Warman ML, Neel BG, Ehrlich MG, Yang W.
  Bone Res. 2018 Apr 6;6:12. doi: 10.1038/s41413-018-0013-z. eCollection 2018.

  PMID: 29644115 Free PMC Article

• Gain-of-function mutations in the gene encoding the tyrosine phosphatase SHP2 induce hydrocephalus in a catalytically dependent manner.
  Zheng H, Yu WM, Waclaw RR, Kontaridis MI, Neel BG, Qu CK.
  Sci Signal. 2018 Mar 20;11(522). pii: eaao1591. doi: 10.1126/scisignal.aao1591.

  PMID: 29559584 Free PMC Article

• A Genomically Characterized Collection of High-Grade Serous Ovarian Cancer Xenografts for Preclinical Testing.
  Cybulska P, Stewart JM, Sayad A, Virtanen C, Shaw PA, Clarke B, Stickle N, Bernardini MQ, Neel BG.
  Am J Pathol. 2018 May;188(5):1120-1131. doi: 10.1016/j.ajpath.2018.01.019. Epub 2018 Feb 16.

  PMID: 29458007

• Affinity purification mass spectrometry analysis of PD-1 uncovers SAP as a new checkpoint inhibitor.
  Peled M, Tocheva AS, Sandigursky S, Nayak S, Philips EA, Nichols KE, Strazza M, Azoulay-Alfaguter I, Askenazi M, Neel BG, Pelzek AJ, Ueberheide B, Mor A.
  Proc Natl Acad Sci U S A. 2018 Jan 16;115(3):E468-E477. doi: 10.1073/pnas.1710437115. Epub 2017 Dec 27.

  PMID: 29282323 Free PMC Article

2017

• Novel combinations of PI3K-mTOR inhibitors with dacomitinib or chemotherapy in PTEN-deficient patient-derived tumor xenografts.
  Brana I, Pham NA, Kim L, Sakashita S, Li M, Ng C, Wang Y, Loparco P, Sierra R, Wang L, Clarke BA, Neel BG, Siu LL, Tsao MS.
  Oncotarget. 2017 Jul 8;8(49):84659-84670. doi: 10.18632/oncotarget.19109. eCollection 2017 Oct 17.

  PMID: 29156674 Free PMC Article

• Deficiency in Protein Tyrosine Phosphatase PTP1B Shortens Lifespan and Leads to Development of Acute Leukemia.
  Le Sommer S, Morrice N, Pesaresi M, Thompson D, Vickers MA, Murray GI, Mody N, Neel BG, Bence KK, Wilson HM, Delibegović M.
  Cancer Res. 2018 Jan 1;78(1):75-87. doi: 10.1158/0008-5472.CAN-17-0946. Epub 2017 Nov 9.

  PMID: 29122767 Free PMC Article

• A ERK/RSK-mediated negative feedback loop regulates M-CSF-evoked PI3K/AKT activation in macrophages.
  Wang L, Iorio C, Yan K, Yang H, Takeshita S, Kang S, Neel BG, Yang W.
  FASEB J. 2018 Feb;32(2):875-887. doi: 10.1096/fj.201700672RR. Epub 2018 Jan 4.

  PMID: 29046360

• Assay to visualize specific protein oxidation reveals spatio-temporal regulation of SHP2.
  Tsutsumi R, Harizanova J, Stockert R, Schröder K, Bastiaens PIH, Neel BG.
  Nat Commun. 2017 Sep 6;8(1):466. doi: 10.1038/s41467-017-00503-w.

  PMID: 28878211 Free PMC Article

• Restoration of TET2 Function Blocks Aberrant Self-Renewal and Leukemia Progression.
  Cimmino L, Dolgalev I, Wang Y, Yoshimi A, Martin GH, Wang J, Ng V, Xia B, Witkowski MT, Mitchell-Flack M, Grillo I, Bakogianni S, Ndiaye-Lobry D, Martín MT, Guillamot M, Banh RS, Xu M, Figueroa ME, Dickins RA, Abdel-Wahab O, Park CY, Tsirigos A, Neel BG, Aifantis I.
  Cell. 2017 Sep 7;170(6):1079-1095.e20. doi: 10.1016/j.cell.2017.07.032. Epub 2017 Aug 17.

  PMID: 28823558 Free PMC Article

• SHP2 is required for BCR-ABL1-induced hematologic neoplasia.
  Gu S, Sayad A, Chan G, Yang W, Lu Z, Virtanen C, Van Etten RA, Neel BG.
  Leukemia. 2018 Jan;32(1):203-213. doi: 10.1038/leu.2017.250. Epub 2017 Aug 14.

  PMID: 28804122 Free PMC Article

• Cellular interplay via cytokine hierarchy causes pathological cardiac hypertrophy in RAF1-mutant Noonan syndrome.
  Yin JC, Platt MJ, Tian X, Wu X, Backx PH, Simpson JA, Araki T, Neel BG.
  Nat Commun. 2017 May 26;8:15518. doi: 10.1038/ncomms15518.

  PMID: 28548091 Free PMC Article

• Critical Role for GAB2 in Neuroblastoma Pathogenesis through the Promotion of SHP2/MYCN Cooperation.
  Zhang X, Dong Z, Zhang C, Ung CY, He S, Tao T, Oliveira AM, Meves A, Ji B, Look AT, Li H, Neel BG, Zhu S.
  Cell Rep. 2017 Mar 21;18(12):2932-2942. doi: 10.1016/j.celrep.2017.02.065.

  PMID: 28329685 Free PMC Article

• Interrogation of Functional Cell-Surface Markers Identifies CD151 Dependency in High-Grade Serous Ovarian Cancer.
  Medrano M, Communal L, Brown KR, Iwanicki M, Normand J, Paterson J, Sircoulomb F, Krzyzanowski P, Novak M, Doodnauth SA, Saiz FS, Cullis J, Al-Awar R, Neel BG, McPherson J, Drapkin R, Ailles L, Mes-Massons AM, Rottapel R.
  Cell Rep. 2017 Mar 7;18(10):2343-2358. doi: 10.1016/j.celrep.2017.02.028.

  PMID: 28273451 Free Article

• Integrated analysis of proteome, phosphotyrosine-proteome, tyrosine-kinome, and tyrosine-phosphatome in acute myeloid leukemia.
  Tong J, Helmy M, Cavalli FM, Jin L, St-Germain J, Karisch R, Taylor P, Minden MD, Taylor MD, Neel BG, Bader GD, Moran MF.
  Proteomics. 2017 Mar;17(6). doi: 10.1002/pmic.201600361.

  PMID: 28176486 Free PMC Article

• A Global Analysis of the Receptor Tyrosine Kinase-Protein Phosphatase Interactome.
  Yao Z, Darowski K, St-Denis N, Wong V, Offensperger F, Villedieu A, Amin S, Malty R, Aoki H, Guo H, Xu Y, Iorio C, Kotlyar M, Emili A, Jurisica I, Neel BG, Babu M, Gingras AC, Stagljar I.
  Mol Cell. 2017 Jan 19;65(2):347-360. doi: 10.1016/j.molcel.2016.12.004. Epub 2017 Jan 5.

  PMID: 28065597 Free PMC Article

2016

• Cancer: Bad neighbours cause bad blood.
  Chan G, Neel BG.
  Nature. 2016 Nov 10;539(7628):173-175. doi: 10.1038/nature19479. Epub 2016 Oct 26. No abstract available.

  PMID: 27783594 Free PMC Article

• Sticking It to Cancer with Molecular Glue for SHP2.
  Ran H, Tsutsumi R, Araki T, Neel BG.
  Cancer Cell. 2016 Aug 8;30(2):194-196. doi: 10.1016/j.ccell.2016.07.010.

  PMID: 27505669 Free PMC Article

• PTP1B controls non-mitochondrial oxygen consumption by regulating RNF213 to promote tumour survival during hypoxia.
  Banh RS, Iorio C, Marcotte R, Xu Y, Cojocari D, Rahman AA, Pawling J, Zhang W, Sinha A, Rose CM, Isasa M, Zhang S, Wu R, Virtanen C, Hitomi T, Habu T, Sidhu SS, Koizumi A, Wilkins SE, Kislinger T, Gygi SP, Schofield CJ, Dennis JW, Wouters BG, Neel BG.
  Nat Cell Biol. 2016 Jul;18(7):803-813. doi: 10.1038/ncb3376. Epub 2016 Jun 20.

  PMID: 27323329 Free PMC Article

• Biochemical Classification of Disease-associated Mutants of RAS-like Protein Expressed in Many Tissues (RIT1).
  Fang Z, Marshall CB, Yin JC, Mazhab-Jafari MT, Gasmi-Seabrook GM, Smith MJ, Nishikawa T, Xu Y, Neel BG, Ikura M.
  J Biol Chem. 2016 Jul 22;291(30):15641-52. doi: 10.1074/jbc.M116.714196. Epub 2016 May 18.

  PMID: 27226556 Free PMC Article

• Distinct GAB2 signaling pathways are essential for myeloid and lymphoid transformation and leukemogenesis by BCR-ABL1.
  Gu S, Chan WW, Mohi G, Rosenbaum J, Sayad A, Lu Z, Virtanen C, Li S, Neel BG, Van Etten RA.
  Blood. 2016 Apr 7;127(14):1803-13. doi: 10.1182/blood-2015-06-653006. Epub 2016 Jan 15.

  PMID: 26773044 Free PMC Article

• Functional Genomic Landscape of Human Breast Cancer Drivers, Vulnerabilities, and Resistance.
  Marcotte R, Sayad A, Brown KR, Sanchez-Garcia F, Reimand J, Haider M, Virtanen C, Bradner JE, Bader GD, Mills GB, Pe’er D, Moffat J, Neel BG.
  Cell. 2016 Jan 14;164(1-2):293-309. doi: 10.1016/j.cell.2015.11.062.

  PMID: 26771497 Free PMC Article

• Gain-of-function mutations of Ptpn11 (Shp2) cause aberrant mitosis and increase susceptibility to DNA damage-induced malignancies.
  Liu X, Zheng H, Li X, Wang S, Meyerson HJ, Yang W, Neel BG, Qu CK.
  Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):984-9. doi: 10.1073/pnas.1508535113. Epub 2016 Jan 11.

  PMID: 26755576 Free PMC Article