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Center for Cancer Research CENTER FOR CANCER RESEARCH Annual Report 2018-2019 Light blue staining shows activated STAT5 in luminal mammary epithelial cells, which is required for terminal differentiation, and the absence of which may be an early step in breast cancer progression. Image created by Nicole Forster PhD Ellisen Laboratory The image is an Immunofluorescence image from induced pluripotent stem (iPS) cells derived from a human patient with an homozygous mutation in the chromatin factor SIRT6. The iPS cells were forced to differentiate into neural progenitors cells, and stained with a neural marker (Nestin-green) and an early embryo marker (Sox2-red). Note that Sox2 is still expressed in these cells (normal NPCs silenced Sox2 at this stage). Image Credit: Christina Ferrer Motoslavsky Laboratory Glioblastoma tumor cells (green) by surrounded and lysed by CAR T cells (red). Image acquired by Ana Castano, MD in Maus lab. Maus Laboratory Multispectral image of a tumor specimen from a head and neck patient. Image courtesy of Joao Oliveira Da Costa, PhD Stott Laboratory Indirect immunofluorescence image of a human RPE-1 exiting mitosis with several missegregation events. Cell was stained for microtubules (red), centromeres (green) and DNA (blue). Image credit: Lilian Kabeche, PhD Zou Laboratory Use of X chromosome reporter to isolate male and female blastocysts for subsequent methylation analysis. Depicted are blastocysts from a cross between male mice carrying an X-linked GFP reporter and wild-type female mice. GFP-positive blastocysts are female while GFP-negative blastocysts are male. Image credit: Jiho Choi Hochedlinger Laboratory CONTENTS Scientific Advisory Board .............................................................................................................................................................. ii Jonathan Kraft Prize / The Annual MGH Award in Cancer Research ............................................................................... iii Center for Cancer Research Faculty ............................................................................................................................................ iv Reports from the Principal Investigators .................................................................................................................................. 1 Reports from the Principal Investigators Martin Aryee ................................................................ 2 Li Lan .............................................................................. 54 Liron Bar-Peled ............................................................ 4 David Langenau ........................................................... 56 Nabeel Bardeesy .......................................................... 6 Michael Lawrence ....................................................... 58 Cyril Benes .................................................................... 8 Shyamala Maheswaran ............................................. 60 Bradley Bernstein ......................................................... 10 Marcela Maus .............................................................. 62 Priscilla Brastianos ...................................................... 12 Andrea McClatchey .................................................... 64 Mark Cobbold ............................................................... 14 David Miyamoto .......................................................... 66 Ryan Corcoran .............................................................. 16 Raul Mostoslavsky ...................................................... 68 Shawn Demehri ............................................................ 18 Mo Motamedi .............................................................. 70 Nick Dyson .................................................................... 20 Christopher Ott ........................................................... 72 Andrew Elia .................................................................... 22 Shiv Pillai ........................................................................ 74 Leif Ellisen ...................................................................... 24 Luca Pinello ................................................................... 76 David Fisher ................................................................... 26 Esther Rheinbay............................................................. 78 Gad Getz ........................................................................ 28 Miguel Rivera ................................................................ 80 Timothy Graubert ........................................................ 30 Dennis Sgroi .................................................................. 82 Wilhelm Haas ............................................................... 32 Toshihiro Shioda ........................................................... 84 Daniel Haber ................................................................. 34 David Spriggs ............................................................... 86 Nir Hacohen .................................................................. 36 Shannon Stott ............................................................... 88 Aaron Hata ................................................................... 38 Mario Suvà .................................................................... 90 Konrad Hochedlinger .................................................. 40 David Sweetser ............................................................ 92 Hanno Hock .................................................................. 42 David Ting ..................................................................... 94 Jonathan Hoggatt ........................................................ 44 Shobha Vasudevan ...................................................... 96 A. John Iafrate .............................................................. 46 Alexandra-Chloé Villani ............................................ 98 Othon Iliopoulos .......................................................... 48 Johnathan Whetstine ............................................... 100 Russell Jenkins ............................................................. 50 Lee Zou ......................................................................... 102 Keith Joung ................................................................... 52 Table of Contents i Scientific Advisory Board 2018 Members Peter Howley, MD Julian Adams, PhD Harvard Medical School Gamida Cell Richard Hynes, PhD Massachusetts Institute of Technology Joan S. Brugge, PhD Harvard Medical School Tyler Jacks, PhD MIT Cancer Center David E. Fisher, MD, PhD Massachusetts General Hospital Alfred G. Knudson Jr., MD, PhD Fox Chase Cancer Center Robert E. Kingston, PhD Massachusetts General Hospital David Livingston, MD Dana-Farber Cancer Institute David N. Louis, MD Massachusetts General Hospital Scott Lowe, PhD Cold Spring Harbor Laboratory Phillip A. Sharp, PhD Massachusetts Institute of Technology Frank McCormick, PhD University of California, San Francisco Arlene Sharpe, MD, PhD Harvard Medical School Stuart Orkin, MD Children’s Hospital and Dana-Farber Cancer Institute Past Members Terry Orr-Weaver, PhD Whitehead Institute Spyros Artavanis-Tsakonas, PhD Yale University School of Medicine Anthony Pawson, FRS, PhD Samuel Lunenfeld Research Institute, Joseph Avruch, MD Mount Sinai Hospital Massachusetts General Hospital Carol Prives, PhD David Baltimore, PhD Columbia University California Institute of Technology Gerald M. Rubin, PhD Cori Bargmann, PhD University of California, Berkeley University of California, San Francisco Gary Ruvkun, PhD Edward J. Benz Jr., MD Massachusetts General Hospital Dana-Farber Cancer Institute Jeffrey Settleman, PhD Donald Ganem, MD Calico, Inc. University of California, San Francisco Eileen White, PhD Walter J. Gehring, PhD Rutgers University Cancer Institute of New Jersey Biozentrum University of Basel David Hogness, PhD Stanford University School of Medicine David Housman, PhD Massachusetts Institute of Technology ii MGH Center For Cancer Research ANNUAL REPORT 2018-2019 Jonathan Kraft Prize for Excellence in Cancer Research Presented by the Massachusetts General Hospital Cancer Center 2019 2016 Carl H. June, MD Joan A. Steitz, PhD Professor in Immunotherapy Sterling Professor of Molecular Biophysics and Biochemistry, Yale Director, Center for Cellular Immunotherapies School of Medicine University of Pennsylvania Perelman School of Medicine 2018 2015 Charles Swanton, MD, PhD C. David Allis, MD, PhD Professor and Chair, Personalized Cancer Medicine Joy and Jack Fishman Professor, Laboratory of Chromatin Biology University College London Cancer Institute, London, UK and Epigenetics, Rockefeller University 2017 Kevan M. Shokat, PhD Professor and Chair, Department of Cellular and Molecular Pharmacology, UCSF Professor, Department of Chemistry, UC Berkeley The Annual MGH Award in Cancer Research In memory of Nathan and Grace Shiff 2014 2009 Hans Clevers, MD, PhD Bert Vogelstein, MD President of the Royal Netherlands Academy of Director of the Ludwig Center for Cancer Genetics & Therapeutics Arts and Sciences Sidney Kimmel Comprehensive Cancer Center Professor of Molecular Genetics Johns Hopkins University, Maryland University Utrecht, Netherlands 2008 2013 Titia de Lange, PhD James Allison, PhD Associate Director of the Anderson Cancer Center Chair, Department of Immunology Rockefeller University, New York MD Anderson Cancer Center,
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