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Cigall Kadoch, PhD

Cigall Kadoch, PhD

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Biography

Cigall Kadoch, PhD

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.

Researcher

Physician

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

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 Respectively
  • 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

    View Dr. Kadoch’s 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.

    Research Departments

    Support my research

    Research Website

    http://www.kadochlab.org

    Publications

      View Dr. Kadoch's Publications

      • Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer. Cancer Cell. 2023 08 14; 41(8):1516-1534.e9. View in: Pubmed

      • Landscape of mSWI/SNF chromatin remodeling complex perturbations in neurodevelopmental disorders. Nat Genet. 2023 08; 55(8):1400-1412. View in: Pubmed

      • The SWI/SNF chromatin-remodeling subunit DPF2 facilitates NRF2-dependent antiinflammatory and antioxidant gene expression. J Clin Invest. 2023 07 03; 133(13). View in: Pubmed

      • DYRK1A promotes viral entry of highly pathogenic human coronaviruses in a kinase-independent manner. PLoS Biol. 2023 06; 21(6):e3002097. View in: Pubmed

      • Structural and functional properties of mSWI/SNF chromatin remodeling complexes revealed through single-cell perturbation screens. Mol Cell. 2023 04 20; 83(8):1350-1367.e7. View in: Pubmed

      • Stepwise activities of mSWI/SNF family chromatin remodeling complexes direct T cell activation and exhaustion. Mol Cell. 2023 04 20; 83(8):1216-1236.e12. View in: Pubmed

      • Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection. Nat Genet. 2023 03; 55(3):471-483. View in: Pubmed

      • A pioneer factor locally opens compacted chromatin to enable targeted ATP-dependent nucleosome remodeling. Nat Struct Mol Biol. 2023 01; 30(1):31-37. View in: Pubmed

      • Arid1a loss potentiates pancreatic ß-cell regeneration through activation of EGF signaling. Cell Rep. 2022 11 01; 41(5):111581. View in: Pubmed

      • SMARCE1 deficiency generates a targetable mSWI/SNF dependency in clear cell meningioma. Nat Genet. 2022 06; 54(6):861-873. View in: Pubmed

      • The FUS::DDIT3 fusion oncoprotein inhibits BAF complex targeting and activity in myxoid liposarcoma. Mol Cell. 2022 05 05; 82(9):1737-1750.e8. View in: Pubmed

      • Synthesis of Oriented Hexasomes and Asymmetric Nucleosomes Using a Template Editing Process. J Am Chem Soc. 2022 02 09; 144(5):2284-2291. View in: Pubmed

      • OCT4 cooperates with distinct ATP-dependent chromatin remodelers in naïve and primed pluripotent states in human. Nat Commun. 2021 08 26; 12(1):5123. View in: Pubmed

      • A functional mammalian display screen identifies rare antibodies that stimulate NK cell-mediated cytotoxicity. Proc Natl Acad Sci U S A. 2021 08 03; 118(31). View in: Pubmed

      • Chromatin landscape signals differentially dictate the activities of mSWI/SNF family complexes. Science. 2021 07 16; 373(6552):306-315. View in: Pubmed

      • Opposing immune and genetic mechanisms shape oncogenic programs in synovial sarcoma. Nat Med. 2021 02; 27(2):289-300. View in: Pubmed

      • Author Correction: The nucleosome acidic patch and H2A ubiquitination underlie mSWI/SNF recruitment in synovial sarcoma. Nat Struct Mol Biol. 2021 Jan; 28(1):118. View in: Pubmed

      • BICRA, a SWI/SNF Complex Member, Is Associated with BAF-Disorder Related Phenotypes in Humans and Model Organisms. Am J Hum Genet. 2020 12 03; 107(6):1096-1112. View in: Pubmed

      • Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection. Cell. 2021 01 07; 184(1):76-91.e13. View in: Pubmed

      • A Structural Model of the Endogenous Human BAF Complex Informs Disease Mechanisms. Cell. 2020 10 29; 183(3):802-817.e24. View in: Pubmed

      • Mammalian SWI/SNF Chromatin Remodeling Complexes: Emerging Mechanisms and Therapeutic Strategies. Trends Genet. 2020 12; 36(12):936-950. View in: Pubmed

      • The nucleosome acidic patch and H2A ubiquitination underlie mSWI/SNF recruitment in synovial sarcoma. Nat Struct Mol Biol. 2020 09; 27(9):836-845. View in: Pubmed

      • ARID1A loss in neuroblastoma promotes the adrenergic-to-mesenchymal transition by regulating enhancer-mediated gene expression. Sci Adv. 2020 07; 6(29):eaaz3440. View in: Pubmed

      • A Novel SS18-SSX Fusion-specific Antibody for the Diagnosis of Synovial Sarcoma. Am J Surg Pathol. 2020 07; 44(7):922-933. View in: Pubmed

      • Synthetic Lethal and Resistance Interactions with BET Bromodomain Inhibitors in Triple-Negative Breast Cancer. Mol Cell. 2020 06 18; 78(6):1096-1113.e8. View in: Pubmed

      • Mammalian SWI/SNF Complex Genomic Alterations and Immune Checkpoint Blockade in Solid Tumors. Cancer Immunol Res. 2020 08; 8(8):1075-1084. View in: Pubmed

      • Genomic and Immunologic Characterization of INI1-Deficient Pediatric Cancers. Clin Cancer Res. 2020 06 15; 26(12):2882-2890. View in: Pubmed

      • ARID1A determines luminal identity and therapeutic response in estrogen-receptor-positive breast cancer. Nat Genet. 2020 02; 52(2):198-207. View in: Pubmed

      • 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. View in: Pubmed

      • Spliceosomal disruption of the non-canonical BAF complex in cancer. Nature. 2019 10; 574(7778):432-436. View in: Pubmed

      • Diverse compositions and functions of chromatin remodeling machines in cancer. Sci Transl Med. 2019 07 17; 11(501). View in: Pubmed

      • Renal medullary carcinomas depend upon SMARCB1 loss and are sensitive to proteasome inhibition. Elife. 2019 03 12; 8. View in: Pubmed

      • 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. View in: Pubmed

      • Chromatin regulatory mechanisms and therapeutic opportunities in cancer. Nat Cell Biol. 2019 02; 21(2):152-161. View in: Pubmed

      • Wiskott-Aldrich syndrome protein (WASP) is a tumor suppressor in T cell lymphoma. Nat Med. 2019 01; 25(1):130-140. View in: Pubmed

      • 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. View in: Pubmed

      • Targeting CDK9 Reactivates Epigenetically Silenced Genes in Cancer. Cell. 2018 11 15; 175(5):1244-1258.e26. View in: Pubmed

      • Modular Organization and Assembly of SWI/SNF Family Chromatin Remodeling Complexes. Cell. 2018 11 15; 175(5):1272-1288.e20. View in: Pubmed

      • Binding of TMPRSS2-ERG to BAF Chromatin Remodeling Complexes Mediates Prostate Oncogenesis. Mol Cell. 2018 08 16; 71(4):554-566.e7. View in: Pubmed

      • 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. View in: Pubmed

      • Interrogation of Mammalian Protein Complex Structure, Function, and Membership Using Genome-Scale Fitness Screens. Cell Syst. 2018 05 23; 6(5):555-568.e7. View in: Pubmed

      • Disruption of mammalian SWI/SNF and polycomb complexes in human sarcomas: mechanisms and therapeutic opportunities. J Pathol. 2018 04; 244(5):638-649. View in: Pubmed

      • 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. View in: Pubmed

      • SMARCB1 is required for widespread BAF complex-mediated activation of enhancers and bivalent promoters. Nat Genet. 2017 Nov; 49(11):1613-1623. View in: Pubmed

      • Cancer-Specific Retargeting of BAF Complexes by a Prion-like Domain. Cell. 2017 Sep 21; 171(1):163-178.e19. View in: Pubmed

      • A SMARCD2-containing mSWI/SNF complex is required for granulopoiesis. Nat Genet. 2017 Apr 26; 49(5):655-657. View in: Pubmed

      • Composition and Function of Mammalian SWI/SNF Chromatin Remodeling Complexes in Human Disease. Cold Spring Harb Symp Quant Biol. 2016; 81:53-60. View in: Pubmed

      • Mammalian SWI/SNF complexes in cancer: emerging therapeutic opportunities. Curr Opin Genet Dev. 2017 Feb; 42:56-67. View in: Pubmed

      • TOP2 synergizes with BAF chromatin remodeling for both resolution and formation of facultative heterochromatin. Nat Struct Mol Biol. 2017 04; 24(4):344-352. View in: Pubmed

      • Dynamics of BAF-Polycomb complex opposition on heterochromatin in normal and oncogenic states. Nat Genet. 2017 Feb; 49(2):213-222. View in: Pubmed

      • Smarca4 ATPase mutations disrupt direct eviction of PRC1 from chromatin. Nat Genet. 2017 Feb; 49(2):282-288. View in: Pubmed

      • Polycomb and trithorax opposition in development and disease. Wiley Interdiscip Rev Dev Biol. 2016 11; 5(6):659-688. View in: Pubmed

      • 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. View in: Pubmed

      • Lifting Up the HAT: Synthetic Lethal Screening Reveals a Novel Vulnerability at the CBP-p300 Axis. Cancer Discov. 2016 Apr; 6(4):350-2. View in: Pubmed

      • PRC2 and SWI/SNF Chromatin Remodeling Complexes in Health and Disease. Biochemistry. 2016 Mar 22; 55(11):1600-14. View in: Pubmed

      • Mammalian SWI/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics. Sci Adv. 2015 Jun; 1(5):e1500447. View in: Pubmed

      • Complement activation and intraventricular rituximab distribution in recurrent central nervous system lymphoma. Clin Cancer Res. 2014 Feb 15; 20(4):1029-41. View in: Pubmed

      • Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Nat Genet. 2013 Jun; 45(6):592-601. View in: Pubmed

      • CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma. Blood. 2013 Jun 06; 121(23):4740-8. View in: Pubmed

      • Reversible disruption of mSWI/SNF (BAF) complexes by the SS18-SSX oncogenic fusion in synovial sarcoma. Cell. 2013 Mar 28; 153(1):71-85. View in: Pubmed

      • Multicenter phase 1 trial of intraventricular immunochemotherapy in recurrent CNS lymphoma. Blood. 2013 Jan 31; 121(5):745-51. View in: Pubmed

      • Biology and treatment of primary central nervous system lymphoma. Neurotherapeutics. 2009 Jul; 6(3):587-97. View in: Pubmed

      • Alcohol as a potential contributing factor in radiation complications. Clin Adv Hematol Oncol. 2009 Apr; 7(4):257-62. View in: Pubmed

      • Pathologic correlates of primary central nervous system lymphoma defined in an orthotopic xenograft model. Clin Cancer Res. 2009 Mar 15; 15(6):1989-97. View in: Pubmed

      • Differential gene expression in central nervous system lymphoma. Blood. 2009 Jan 01; 113(1):266-7; author reply 267-8. View in: Pubmed

      • Protein biomarker identification in the CSF of patients with CNS lymphoma. J Clin Oncol. 2008 Jan 01; 26(1):96-105. View in: Pubmed

      • Molecular pathogenesis of primary central nervous system lymphoma. Neurosurg Focus. 2006 Nov 15; 21(5):E1. View in: Pubmed

      • When prostate brachytherapy fails: a case report and discussion. Oncologist. 2005 Nov-Dec; 10(10):799-805. View in: Pubmed

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