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Cigall Kadoch, PhD


Researcher


Researcher

  • Associate Professor of Pediatrics, Harvard Medical School
  • Institute Member, Broad Institute of MIT and Harvard
  • Co-Director, Epigenomics Program, Broad Institute of MIT and Harvard

Contact Information

  • Office Phone Number617-632-3789

Bio

Cigall Kadoch, Ph.D., is an Associate Professor of Pediatric Oncology at the Dana-Farber Cancer Institute and Harvard Medical School, Affiliate Faculty of Biological Chemistry and Molecular Biology at Harvard Medical School, and Institute Member and Epigenomics Program Co-Director at the Broad Institute of MIT and Harvard.

She established her independent laboratory in 2014, at age 28, one of the youngest scientists ever appointed to the Harvard Medical School faculty, immediately following completion of her Ph.D. studies in Cancer Biology at Stanford University. She has quickly become a leading expert in chromatin and gene regulation and is internationally recognized for her groundbreaking studies in these areas. Specifically, her laboratory studies the structure and function of chromatin remodeling complexes such as the mammalian SWI/SNF (or BAF) complex, with emphasis on defining the mechanisms underlying cancer-specific perturbations. Of note, the recent surge in exome- and genome-wide sequencing efforts has unmasked a major, previously unappreciated contribution of these regulators to malignancy. Indeed, the genes encoding subunits of mammalian SWI/SNF complexes are mutated in over 25% of human cancers.

Dr. Kadoch has received numerous prestigious awards and research grants to support her academic laboratory at Harvard, including the NIH Director's New Innovator Award, the Pew Scholar Award, the American Cancer Society Research Scholar Award, the American Association for the Advancement of Sciences (AAAS) Marin and Rose Wachtel Cancer Research Prize, and the American Association for Cancer Research (AACR) Outstanding Achievement in Basic Cancer Research Award. Additionally, over the past several years, she was named to the Forbes 30 under 30 list, MIT Technology Review 35 Innovators Under 35, Popular Science Brilliant 10, Business Insider Top 30 Young leaders in Biopharma and was recently named a Blavatnik National Awards Finalist.

Recent Awards:

  • American Association for Cancer Research Outstanding Achievement in Basic Cancer Research, 2020
  • Blavatnik National Awards, Finalist, 2020
  • Early Career Life Scientist Award, American Society for Cell Biology, 2019
  • American Association for the Advancement of Science (AAAS) Martin and Rose Wachtel Cancer Research Prize, 2019
  • Inaugural Liddy Shriver Career Research Award, Liddy Shriver Sarcoma Foundation and the Connective Tissue Oncology Society (CTOS), 2018
  • Broad-Israel Science Foundation Collaborative Research Award, 2018
  • Alex's Lemonade Stand Foundation (ALSF) 'A Award' and Young Investigator Award, 2018 and 2015 Respectiviely
  • USA Today ‘Our Women in Healthcare’ (USA TODAY), 2018
  • Top 40 Under 40 in Cancer Research (The Lynx Group), 2018
  • Endpoints Under 40 List of Biopharma Professionals (Endpoints), 2018
  • Business Insider’s 30 Under 40 Top Leaders in Biotechnology and Pharma (Business Insider), 2018
  • Wilson S. Stone Memorial Award and Lecture (MD Anderson Cancer Center), 2017
  • Popular Science Brilliant 10 (Popular Science), 2016
  • Bayer Early Excellence in Science Award (Bayer Health Care), 2015
  • MIT Technology Review Innovators Under 35 (MIT Technology Review), 2015
  • Merkin Institute Distinguished Fellow- Broad Institute, 2015
  • Pew-Stewart Scholars in Cancer Research Award- Pew Charitable Trust, 2015
  • NIH Director’s New Innovator Award (DP2)- National Institutes of Health, 2014
  • American Cancer Society Research Scholar Award- American Cancer Society, 2015
  • Forbes Top 30 Under 30 in Science and Healthcare (Forbes, Inc.), 2014
  • American Association for Cancer Research (AACR) Scholar Award (AACR), 2013

Research

The 25-member Kadoch Laboratory, located at the Dana-Farber, uses multidisciplinary approaches to unravel chromatin and gene regulatory mechanisms, including biochemistry, biophysics, structural biology, human genetics, genomics, epigenomics, and systems and computational biology. We focus on large protein complexes known as ATP-dependent chromatin remodeling complexes, with emphasis on the mammalian SWI/SNF (mSWI/SNF) family, which play critical roles in governing genomic architecture and gene expression. These macromolecular machines are among the most diverse and heterogeneous enzyme-driven entities encoded by the mammalian genome, each containing a central catalytic ATPase member along with additional subunits that play specialized structural or functional roles to enable alteration of DNA-nucleosome contacts. The genes encoding chromatin remodeling complex components are frequently mutated in disease, with mammalian SWI/SNF (mSWI/SNF) complex subunits disrupted in >20% of human cancers as well as several neurodevelopmental disorders, often as sole genetic drivers, making them the most frequently perturbed chromatin regulatory family profiled to date. Such compelling and rapidly expanding human genetics coupled with an incomplete understanding and unmet biochemical challenges has inspired our comprehensive studies in to the structure and function of mammalian chromatin remodelers. Our work to date has informed new mechanistic principles of this broadly important cellular machinery in health and disease, providing requisite foundations for the development of new therapeutic approaches.

Mashtalir N, Suzuki H, Farrell DP, Sankar A, Luo J, Filipovski M, D'Avino AR, St Pierre R, Valencia AM, Onikubo T, Roeder RG, Han Y, He Y, Ranish JA, DiMaio F, Walz T, Kadoch C. A Structural Model of the Endogenous Human BAF Complex Informs Disease Mechanisms. Cell. 2020 Oct 29; 183(3):802-817.e24.
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Centore RC, Sandoval GJ, Soares LMM, Kadoch C, Chan HM. Mammalian SWI/SNF Chromatin Remodeling Complexes: Emerging Mechanisms and Therapeutic Strategies. Trends Genet. 2020 Dec; 36(12):936-950.
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McBride MJ, Mashtalir N, Winter EB, Dao HT, Filipovski M, D'Avino AR, Seo HS, Umbreit NT, St Pierre R, Valencia AM, Qian K, Zullow HJ, Jaffe JD, Dhe-Paganon S, Muir TW, Kadoch C. The nucleosome acidic patch and H2A ubiquitination underlie mSWI/SNF recruitment in synovial sarcoma. Nat Struct Mol Biol. 2020 09; 27(9):836-845.
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Shi H, Tao T, Abraham BJ, Durbin AD, Zimmerman MW, Kadoch C, Look AT. ARID1A loss in neuroblastoma promotes the adrenergic-to-mesenchymal transition by regulating enhancer-mediated gene expression. Sci Adv. 2020 Jul; 6(29):eaaz3440.
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Baranov E, McBride MJ, Bellizzi AM, Ligon AH, Fletcher CDM, Kadoch C, Hornick JL. A Novel SS18-SSX Fusion-specific Antibody for the Diagnosis of Synovial Sarcoma. Am J Surg Pathol. 2020 07; 44(7):922-933.
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Shu S, Wu HJ, Ge JY, Zeid R, Harris IS, Jovanovic B, Murphy K, Wang B, Qiu X, Endress JE, Reyes J, Lim K, Font-Tello A, Syamala S, Xiao T, Reddy Chilamakuri CS, Papachristou EK, D'Santos C, Anand J, Hinohara K, Li W, McDonald TO, Luoma A, Modiste RJ, Nguyen QD, Michel B, Cejas P, Kadoch C, Jaffe JD, Wucherpfennig KW, Qi J, Liu XS, Long H, Brown M, Carroll JS, Brugge JS, Bradner J, Michor F, Polyak K. Synthetic Lethal and Resistance Interactions with BET Bromodomain Inhibitors in Triple-Negative Breast Cancer. Mol Cell. 2020 06 18; 78(6):1096-1113.e8.
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Abou Alaiwi S, Nassar AH, Xie W, Bakouny Z, Berchuck JE, Braun DA, Baca SC, Nuzzo PV, Flippot R, Mouhieddine TH, Spurr LF, Li YY, Li T, Flaifel A, Steinharter JA, Margolis CA, Vokes NI, Du H, Shukla SA, Cherniack AD, Sonpavde G, Haddad RI, Awad MM, Giannakis M, Hodi FS, Liu XS, Signoretti S, Kadoch C, Freedman ML, Kwiatkowski DJ, Van Allen EM, Choueiri TK. Mammalian SWI/SNF Complex Genomic Alterations and Immune Checkpoint Blockade in Solid Tumors. Cancer Immunol Res. 2020 08; 8(8):1075-1084.
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Forrest SJ, Al-Ibraheemi A, Doan D, Ward A, Clinton CM, Putra J, Pinches RS, Kadoch C, Chi SN, DuBois SG, Leavey PJ, LeBoeuf NR, Mullen E, Collins N, Church AJ, Janeway KA. Genomic and Immunologic Characterization of INI1-Deficient Pediatric Cancers. Clin Cancer Res. 2020 Jun 15; 26(12):2882-2890.
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Xu G, Chhangawala S, Cocco E, Razavi P, Cai Y, Otto JE, Ferrando L, Selenica P, Ladewig E, Chan C, Da Cruz Paula A, Witkin M, Cheng Y, Park J, Serna-Tamayo C, Zhao H, Wu F, Sallaku M, Qu X, Zhao A, Collings CK, D'Avino AR, Jhaveri K, Koche R, Levine RL, Reis-Filho JS, Kadoch C, Scaltriti M, Leslie CS, Baselga J, Toska E. ARID1A determines luminal identity and therapeutic response in estrogen-receptor-positive breast cancer. Nat Genet. 2020 02; 52(2):198-207.
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Valencia AM, Collings CK, Dao HT, St Pierre R, Cheng YC, Huang J, Sun ZY, Seo HS, Mashtalir N, Comstock DE, Bolonduro O, Vangos NE, Yeoh ZC, Dornon MK, Hermawan C, Barrett L, Dhe-Paganon S, Woolf CJ, Muir TW, Kadoch C. Recurrent SMARCB1 Mutations Reveal a Nucleosome Acidic Patch Interaction Site That Potentiates mSWI/SNF Complex Chromatin Remodeling. Cell. 2019 11 27; 179(6):1342-1356.e23.
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Inoue D, Chew GL, Liu B, Michel BC, Pangallo J, D'Avino AR, Hitchman T, North K, Lee SC, Bitner L, Block A, Moore AR, Yoshimi A, Escobar-Hoyos L, Cho H, Penson A, Lu SX, Taylor J, Chen Y, Kadoch C, Abdel-Wahab O, Bradley RK. Spliceosomal disruption of the non-canonical BAF complex in cancer. Nature. 2019 10; 574(7778):432-436.
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Kadoch C. Diverse compositions and functions of chromatin remodeling machines in cancer. Sci Transl Med. 2019 07 17; 11(501).
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Hong AL, Tseng YY, Wala JA, Kim WJ, Kynnap BD, Doshi MB, Kugener G, Sandoval GJ, Howard TP, Li J, Yang X, Tillgren M, Ghandi M, Sayeed A, Deasy R, Ward A, McSteen B, Labella KM, Keskula P, Tracy A, Connor C, Clinton CM, Church AJ, Crompton BD, Janeway KA, Van Hare B, Sandak D, Gjoerup O, Bandopadhayay P, Clemons PA, Schreiber SL, Root DE, Gokhale PC, Chi SN, Mullen EA, Roberts CW, Kadoch C, Beroukhim R, Ligon KL, Boehm JS, Hahn WC. Renal medullary carcinomas depend upon SMARCB1 loss and are sensitive to proteasome inhibition. Elife. 2019 03 12; 8.
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Pan J, McKenzie ZM, D'Avino AR, Mashtalir N, Lareau CA, St Pierre R, Wang L, Shilatifard A, Kadoch C. The ATPase module of mammalian SWI/SNF family complexes mediates subcomplex identity and catalytic activity-independent genomic targeting. Nat Genet. 2019 04; 51(4):618-626.
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Valencia AM, Kadoch C. Chromatin regulatory mechanisms and therapeutic opportunities in cancer. Nat Cell Biol. 2019 02; 21(2):152-161.
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Menotti M, Ambrogio C, Cheong TC, Pighi C, Mota I, Cassel SH, Compagno M, Wang Q, Dall'Olio R, Minero VG, Poggio T, Sharma GG, Patrucco E, Mastini C, Choudhari R, Pich A, Zamo A, Piva R, Giliani S, Mologni L, Collings CK, Kadoch C, Gambacorti-Passerini C, Notarangelo LD, Anton IM, Voena C, Chiarle R. Wiskott-Aldrich syndrome protein (WASP) is a tumor suppressor in T cell lymphoma. Nat Med. 2019 01; 25(1):130-140.
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Michel BC, D'Avino AR, Cassel SH, Mashtalir N, McKenzie ZM, McBride MJ, Valencia AM, Zhou Q, Bocker M, Soares LMM, Pan J, Remillard DI, Lareau CA, Zullow HJ, Fortoul N, Gray NS, Bradner JE, Chan HM, Kadoch C. A non-canonical SWI/SNF complex is a synthetic lethal target in cancers driven by BAF complex perturbation. Nat Cell Biol. 2018 12; 20(12):1410-1420.
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Zhang H, Pandey S, Travers M, Sun H, Morton G, Madzo J, Chung W, Khowsathit J, Perez-Leal O, Barrero CA, Merali C, Okamoto Y, Sato T, Pan J, Garriga J, Bhanu NV, Simithy J, Patel B, Huang J, Raynal NJ, Garcia BA, Jacobson MA, Kadoch C, Merali S, Zhang Y, Childers W, Abou-Gharbia M, Karanicolas J, Baylin SB, Zahnow CA, Jelinek J, Graña X, Issa JJ. Targeting CDK9 Reactivates Epigenetically Silenced Genes in Cancer. Cell. 2018 11 15; 175(5):1244-1258.e26.
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Mashtalir N, D'Avino AR, Michel BC, Luo J, Pan J, Otto JE, Zullow HJ, McKenzie ZM, Kubiak RL, St Pierre R, Valencia AM, Poynter SJ, Cassel SH, Ranish JA, Kadoch C. Modular Organization and Assembly of SWI/SNF Family Chromatin Remodeling Complexes. Cell. 2018 11 15; 175(5):1272-1288.e20.
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Sandoval GJ, Pulice JL, Pakula H, Schenone M, Takeda DY, Pop M, Boulay G, Williamson KE, McBride MJ, Pan J, St Pierre R, Hartman E, Garraway LA, Carr SA, Rivera MN, Li Z, Ronco L, Hahn WC, Kadoch C. Binding of TMPRSS2-ERG to BAF Chromatin Remodeling Complexes Mediates Prostate Oncogenesis. Mol Cell. 2018 08 16; 71(4):554-566.e7.
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McBride MJ, Pulice JL, Beird HC, Ingram DR, D'Avino AR, Shern JF, Charville GW, Hornick JL, Nakayama RT, Garcia-Rivera EM, Araujo DM, Wang WL, Tsai JW, Yeagley M, Wagner AJ, Futreal PA, Khan J, Lazar AJ, Kadoch C. The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma. Cancer Cell. 2018 06 11; 33(6):1128-1141.e7.
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Pan J, Meyers RM, Michel BC, Mashtalir N, Sizemore AE, Wells JN, Cassel SH, Vazquez F, Weir BA, Hahn WC, Marsh JA, Tsherniak A, Kadoch C. Interrogation of Mammalian Protein Complex Structure, Function, and Membership Using Genome-Scale Fitness Screens. Cell Syst. 2018 05 23; 6(5):555-568.e7.
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McBride MJ, Kadoch C. Disruption of mammalian SWI/SNF and polycomb complexes in human sarcomas: mechanisms and therapeutic opportunities. J Pathol. 2018 04; 244(5):638-649.
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Otto JE, Kadoch C. A Two-Faced mSWI/SNF Subunit: Dual Roles for ARID1A in Tumor Suppression and Oncogenicity in the Liver. Cancer Cell. 2017 11 13; 32(5):542-543.
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Nakayama RT, Pulice JL, Valencia AM, McBride MJ, McKenzie ZM, Gillespie MA, Ku WL, Teng M, Cui K, Williams RT, Cassel SH, Qing H, Widmer CJ, Demetri GD, Irizarry RA, Zhao K, Ranish JA, Kadoch C. SMARCB1 is required for widespread BAF complex-mediated activation of enhancers and bivalent promoters. Nat Genet. 2017 Nov; 49(11):1613-1623.
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Boulay G, Sandoval GJ, Riggi N, Iyer S, Buisson R, Naigles B, Awad ME, Rengarajan S, Volorio A, McBride MJ, Broye LC, Zou L, Stamenkovic I, Kadoch C, Rivera MN. Cancer-Specific Retargeting of BAF Complexes by a Prion-like Domain. Cell. 2017 Sep 21; 171(1):163-178.e19.
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Michel BC, Kadoch C. A SMARCD2-containing mSWI/SNF complex is required for granulopoiesis. Nat Genet. 2017 Apr 26; 49(5):655-657.
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Pulice JL, Kadoch C. Composition and Function of Mammalian SWI/SNF Chromatin Remodeling Complexes in Human Disease. Cold Spring Harb Symp Quant Biol. 2016; 81:53-60.
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St Pierre R, Kadoch C. Mammalian SWI/SNF complexes in cancer: emerging therapeutic opportunities. Curr Opin Genet Dev. 2017 Feb; 42:56-67.
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Miller EL, Hargreaves DC, Kadoch C, Chang CY, Calarco JP, Hodges C, Buenrostro JD, Cui K, Greenleaf WJ, Zhao K, Crabtree GR. TOP2 synergizes with BAF chromatin remodeling for both resolution and formation of facultative heterochromatin. Nat Struct Mol Biol. 2017 04; 24(4):344-352.
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Kadoch C, Williams RT, Calarco JP, Miller EL, Weber CM, Braun SM, Pulice JL, Chory EJ, Crabtree GR. Dynamics of BAF-Polycomb complex opposition on heterochromatin in normal and oncogenic states. Nat Genet. 2017 Feb; 49(2):213-222.
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Stanton BZ, Hodges C, Calarco JP, Braun SM, Ku WL, Kadoch C, Zhao K, Crabtree GR. Smarca4 ATPase mutations disrupt direct eviction of PRC1 from chromatin. Nat Genet. 2017 Feb; 49(2):282-288.
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Poynter ST, Kadoch C. Polycomb and trithorax opposition in development and disease. Wiley Interdiscip Rev Dev Biol. 2016 11; 5(6):659-688.
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Hingorani P, Janeway K, Crompton BD, Kadoch C, Mackall CL, Khan J, Shern JF, Schiffman J, Mirabello L, Savage SA, Ladanyi M, Meltzer P, Bult CJ, Adamson PC, Lupo PJ, Mody R, DuBois SG, Parsons DW, Khanna C, Lau C, Hawkins DS, Randall RL, Smith M, Sorensen PH, Plon SE, Skapek SX, Lessnick S, Gorlick R, Reed DR. Current state of pediatric sarcoma biology and opportunities for future discovery: A report from the sarcoma translational research workshop. Cancer Genet. 2016 05; 209(5):182-94.
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Kadoch C. Lifting Up the HAT: Synthetic Lethal Screening Reveals a Novel Vulnerability at the CBP-p300 Axis. Cancer Discov. 2016 Apr; 6(4):350-2.
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Kadoch C, Copeland RA, Keilhack H. PRC2 and SWI/SNF Chromatin Remodeling Complexes in Health and Disease. Biochemistry. 2016 Mar 22; 55(11):1600-14.
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Kadoch C, Crabtree GR. Mammalian SWI/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics. Sci Adv. 2015 Jun; 1(5):e1500447.
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Kadoch C, Li J, Wong VS, Chen L, Cha S, Munster P, Lowell CA, Shuman MA, Rubenstein JL. Complement activation and intraventricular rituximab distribution in recurrent central nervous system lymphoma. Clin Cancer Res. 2014 Feb 15; 20(4):1029-41.
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Kadoch C, Hargreaves DC, Hodges C, Elias L, Ho L, Ranish J, Crabtree GR. Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Nat Genet. 2013 Jun; 45(6):592-601.
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Rubenstein JL, Wong VS, Kadoch C, Gao HX, Barajas R, Chen L, Josephson SA, Scott B, Douglas V, Maiti M, Kaplan LD, Treseler PA, Cha S, Hwang JH, Cinque P, Cyster JG, Lowell C. CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma. Blood. 2013 Jun 06; 121(23):4740-8.
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Kadoch C, Crabtree GR. Reversible disruption of mSWI/SNF (BAF) complexes by the SS18-SSX oncogenic fusion in synovial sarcoma. Cell. 2013 Mar 28; 153(1):71-85.
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Rubenstein JL, Li J, Chen L, Advani R, Drappatz J, Gerstner E, Batchelor T, Krouwer H, Hwang J, Auerback G, Kadoch C, Lowell C, Munster P, Cha S, Shuman MA, Damon LE. Multicenter phase 1 trial of intraventricular immunochemotherapy in recurrent CNS lymphoma. Blood. 2013 Jan 31; 121(5):745-51.
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Algazi AP, Kadoch C, Rubenstein JL. Biology and treatment of primary central nervous system lymphoma. Neurotherapeutics. 2009 Jul; 6(3):587-97.
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Matthews RH, Kadoch C, Ercal N. Alcohol as a potential contributing factor in radiation complications. Clin Adv Hematol Oncol. 2009 Apr; 7(4):257-62.
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Kadoch C, Dinca EB, Voicu R, Chen L, Nguyen D, Parikh S, Karrim J, Shuman MA, Lowell CA, Treseler PA, James CD, Rubenstein JL. Pathologic correlates of primary central nervous system lymphoma defined in an orthotopic xenograft model. Clin Cancer Res. 2009 Mar 15; 15(6):1989-97.
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Rubenstein JL, Shen A, Batchelor TT, Kadoch C, Treseler P, Shuman MA. Differential gene expression in central nervous system lymphoma. Blood. 2009 Jan 01; 113(1):266-7; author reply 267-8.
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Roy S, Josephson SA, Fridlyand J, Karch J, Kadoch C, Karrim J, Damon L, Treseler P, Kunwar S, Shuman MA, Jones T, Becker CH, Schulman H, Rubenstein JL. Protein biomarker identification in the CSF of patients with CNS lymphoma. J Clin Oncol. 2008 Jan 01; 26(1):96-105.
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Kadoch C, Treseler P, Rubenstein JL. Molecular pathogenesis of primary central nervous system lymphoma. Neurosurg Focus. 2006 Nov 15; 21(5):E1.
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Kadoch C, D'Amico AV, Matthews RH. When prostate brachytherapy fails: a case report and discussion. Oncologist. 2005 Nov-Dec; 10(10):799-805.
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