Photo of Cigall Kadoch, PhD

Cigall Kadoch, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute


cigall_kadoch@dfci.harvard.edu

Photo of Cigall Kadoch, PhD

Dana-Farber Cancer Institute


cigall_kadoch@dfci.harvard.edu

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Cigall Kadoch, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Associate Professor, Pediatrics, Harvard Medical School
  • Associate Professor, Pediatric Oncology, Dana-Farber Cancer Institute
  • Principal Investigator, Pediatric Oncology, Dana-Farber Cancer Institute
  • Institute Member and Co-Director, Epigenomics Program, Cancer Program, Broad Institute of MIT and Harvard
  • Associate Professor, Pediatrics, Harvard Medical School
  • Affiliated Faculty, Biological Chemistry and Molecular Pharmacology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

Recent whole-genome sequencing studies of human cancers and other diseases have heralded the discovery of several new, surprising classes of genes not previously known to play causal oncogenic roles. One of the most significant findings unveiled in these genetic studies is the high mutation frequency in genes involved in epigenomic and chromatin biology-based processes. The most frequent and widespread among them are mutations in the genes encoding subunits of the mammalian SWI/SNF (mSWI/SNF or BAF) family of ATP-dependent chromatin remodeling complexes, recurrently perturbed in >20% of all human cancers. The central focus of our laboratory is to understand the structure and function of this large, diverse class of chromatin remodeling machines and to define their roles in human disease.

Publications from Harvard Catalyst Profiles

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  • Kang E, Kadoch C, Rubenstein JL, Lanier LL, Wells JA. A functional mammalian display screen identifies rare antibodies that stimulate NK cell-mediated cytotoxicity. Proc Natl Acad Sci U S A 2021. PubMed
  • Mashtalir N, Dao HT, Sankar A, Liu H, Corin AJ, Bagert JD, Ge EJ, D'Avino AR, Filipovski M, Michel BC, Dann GP, Muir TW, Kadoch C. Chromatin landscape signals differentially dictate the activities of mSWI/SNF family complexes. Science 2021; 373:306-315. PubMed
  • Huang X, Park KM, Gontarz P, Zhang B, Pan J, McKenzie Z, Fischer LA, Dong C, Dietmann S, Xing X, Shliaha PV, Yang J, Li D, Ding J, Lungjangwa T, Mitalipova M, Khan SA, Imsoonthornruksa S, Jensen N, Wang T, Kadoch C, Jaenisch R, Wang J, Theunissen TW. OCT4 cooperates with distinct ATP-dependent chromatin remodelers in naïve and primed pluripotent states in human. Nat Commun 2021; 12:5123. PubMed
  • Jerby-Arnon L, Neftel C, Shore ME, Weisman HR, Mathewson ND, McBride MJ, Haas B, Izar B, Volorio A, Boulay G, Cironi L, Richman AR, Broye LC, Gurski JM, Luo CC, Mylvaganam R, Nguyen L, Mei S, Melms JC, Georgescu C, Cohen O, Buendia-Buendia JE, Segerstolpe A, Sud M, Cuoco MS, Labes D, Gritsch S, Zollinger DR, Ortogero N, Beechem JM, Petur Nielsen G, Chebib I, Nguyen-Ngoc T, Montemurro M, Cote GM, Choy E, Letovanec I, Cherix S, Wagle N, Sorger PK, Haynes AB, Mullen JT, Stamenkovic I, Rivera MN, Kadoch C, Wucherpfennig KW, Rozenblatt-Rosen O, Suvà ML, Riggi N, Regev A. Opposing immune and genetic mechanisms shape oncogenic programs in synovial sarcoma. Nat Med 2021; 27:289-300. PubMed
  • 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; 183:802-817.e24. PubMed
  • 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; 27:836-845. PubMed
  • Centore RC, Sandoval GJ, Soares LMM, Kadoch C, Chan HM. Mammalian SWI/SNF Chromatin Remodeling Complexes: Emerging Mechanisms and Therapeutic Strategies. Trends Genet 2020. PubMed
  • 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; 6:eaaz3440. PubMed
  • Shu S, Wu HJ, Ge JY, Zeid R, Harris IS, Jovanović 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; 78:1096-1113.e8. PubMed
  • 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. PubMed
  • 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. PubMed
  • Forrest SJ, Al-Ibraheemi A, Doan D, Ward A, Clinton CM, Putra J, Pinches RS, Kadoch C, Chi S, Dubois SG, Leavey P, LeBoeuf NR, Mullen E, Collins N, Church AJ, Janeway KA. Genomic and immunologic characterization of INI1-deficient pediatric cancers. Clin Cancer Res 2020. PubMed
  • 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; 52:198-207. PubMed
  • Barish S, Barakat TS, Michel BC, Mashtalir N, Phillips JB, Valencia AM, Ugur B, Wegner J, Scott TM, Bostwick B, , Murdock DR, Dai H, Perenthaler E, Nikoncuk A, van Slegtenhorst M, Brooks AS, Keren B, Nava C, Mignot C, Douglas J, Rodan L, Nowak C, Ellard S, Stals K, Lynch SA, Faoucher M, Lesca G, Edery P, Engleman KL, Zhou D, Thiffault I, Herriges J, Gass J, Louie RJ, Stolerman E, Washington C, Vetrini F, Otsubo A, Pratt VM, Conboy E, Treat K, Shannon N, Camacho J, Wakeling E, Yuan B, Chen CA, Rosenfeld JA, Westerfield M, Wangler M, Yamamoto S, Kadoch C, Scott DA, Bellen HJ. BICRA, a SWI/SNF Complex Member, Is Associated with BAF-Disorder Related Phenotypes in Humans and Model Organisms. Am J Hum Genet 2020; 107:1096-1112. PubMed
  • 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; 179:1342-1356.e23. PubMed
  • Kadoch C. Diverse compositions and functions of chromatin remodeling machines in cancer. Sci Transl Med 2019. PubMed
  • 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; 51:618-626. PubMed
  • 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 loss and are sensitive to proteasome inhibition. Elife 2019. PubMed
  • Valencia AM, Kadoch C. Chromatin regulatory mechanisms and therapeutic opportunities in cancer. Nat Cell Biol 2019. PubMed
  • 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; 574:432-436. PubMed
  • 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 2018. PubMed
  • 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; 20:1410-1420. PubMed
  • 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; 175:1272-1288.e20. PubMed
  • 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; 175:1244-1258.e26. PubMed
  • 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; 71:554-566.e7. PubMed
  • 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; 33:1128-1141.e7. PubMed
  • 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; 6:555-568.e7. PubMed
  • McBride MJ, Kadoch C. Disruption of mammalian SWI/SNF and polycomb complexes in human sarcomas: mechanisms and therapeutic opportunities. J Pathol 2018; 244:638-649. PubMed
  • 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; 32:542-543. PubMed
  • 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. PubMed
  • 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; 171:163-178.e19. PubMed
  • Michel BC, Kadoch C. A SMARCD2-containing mSWI/SNF complex is required for granulopoiesis. Nat Genet 2017; 49:655-657. PubMed
  • Pierre RS, Kadoch C. Mammalian SWI/SNF complexes in cancer: emerging therapeutic opportunities. Curr Opin Genet Dev 2017; 42:56-67. PubMed
  • 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; 24:344-352. PubMed
  • 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; 49:282-288. PubMed
  • 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; 49:213-222. PubMed
  • Poynter ST, Kadoch C. Polycomb and trithorax opposition in development and disease. Wiley Interdiscip Rev Dev Biol 2016. PubMed
  • 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; 209:182-94. PubMed
  • Kadoch C. Lifting Up the HAT: Synthetic Lethal Screening Reveals a Novel Vulnerability at the CBP-p300 Axis. 2016; 6:350-2. PubMed
  • Kadoch C, Copeland RA, Keilhack H. PRC2 and SWI/SNF Chromatin Remodeling Complexes in Health and Disease. Biochemistry 2016; 55:1600-14. PubMed
  • 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. PubMed
  • Kadoch C, Crabtree GR. Mammalian SWI/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics. Sci Adv 2015; 1:e1500447. PubMed
  • 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. PubMed
  • 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; 121:4740-8. PubMed
  • 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; 45:592-601. PubMed
  • Kadoch C, Crabtree GR. Reversible disruption of mSWI/SNF (BAF) complexes by the SS18-SSX oncogenic fusion in synovial sarcoma. Cell 2013; 153:71-85. PubMed
  • 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; 121:745-51. PubMed
  • Algazi AP, Kadoch C, Rubenstein JL. Biology and treatment of primary central nervous system lymphoma. 2009; 6:587-97. PubMed
  • 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; 15:1989-97. PubMed
  • Rubenstein JL,Shen A,Batchelor TT,Kadoch C,Treseler P,Shuman MA. Differential gene expression in central nervous system lymphoma. Blood 2009; 113:266-7; author reply 267-8. PubMed
  • 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; 26:96-105. PubMed
  • Kadoch C, Treseler P, Rubenstein JL. Molecular pathogenesis of primary central nervous system lymphoma. Neurosurg Focus 2006; 21:E1. PubMed
  • Kadoch C, D'Amico AV, Matthews RH. When prostate brachytherapy fails: a case report and discussion. Oncologist 2005; 10:799-805. PubMed
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DF/HCC members that share similar concepts* with Cigall Kadoch, PhD but have yet to coauthor a publication with this researcher.

* Concepts are MeSH terms, automatically derived from member publications

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