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Center for Cancer Research ANNUAL REPORT 2019-2020 Daniel Haber Photo by Scott Eisen in Cancer Research and Symposium Presented by the Our Research Program

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Center for Cancer Research ANNUAL REPORT 2019-2020 Daniel Haber Photo by Scott Eisen in Cancer Research and Symposium Presented by the Our Research Program CENTER FOR CANCER RESEARCH CANCER CENTER FOR ANNUAL REPORT 2019-2020 CENTER for CANCER RESEARCH Annual Report 2019-2020 Massachusetts General Hospital Cancer Center Cancer Hospital General Massachusetts CENTER FOR CANCER RESEARCH Charlestown Laboratories Building 149, 13th Street Charlestown, MA 02129 Jackson Laboratories Jackson Building 55 Fruit Street Boston, MA 02114 Simches Laboratories CPZN 4200 185 Cambridge Street Boston, MA 02114 www.massgeneral.org/cancerresearch/ Microfluidic device for the generation of droplets containing mixed cell populations for long term culture. Image courtesy of Rohan Thakur, Stott Laboratory Ex vivo culture of circulating tumor cells from a breast cancer patient. Image courtesy of Haber/Maheswaran Laboratory EGF stimulation rapidly triggers actin/ERM- (green) and pAkt (red) rich macropinocytic cups on the surface of Nf2-/- cells. Image courtesy of Christine Chiasson-MacKenzie, PhD, McClatchey Laboratory Report design by Catalano Design; Cover background photo by Lee Hopkins, OLP Creative Hopkins, OLP Creative Lee by photo Design; Cover background Catalano Report design by CONTENTS Message from the Director ................................................................................................................................... ii Kurt J. Isselbacher – In Memoriam ..................................................................................................................... iv Scientific Advisory Board ...................................................................................................................................... vi Jonathan Kraft Prize / The Annual MGH Award in Cancer Research ................................................................. vii Center for Cancer Research Faculty .................................................................................................................... viii Reports from the Principal Investigators ............................................................................................................ 1 Reports from the Principal Investigators Martin Aryee ....................................................... 2 Li Lan ................................................................. 52 Liron Bar-Peled .................................................. 4 David M. Langenau ............................................. 54 Nabeel Bardeesy ................................................ 6 Michael S. Lawrence .......................................... 56 Cyril Benes ......................................................... 8 Shyamala Maheswaran ...................................... 58 Bradley Bernstein .............................................. 10 Robert Manguso ................................................. 60 Priscilla K. Brastianos ....................................... 12 Marcela V. Maus ................................................. 62 Ryan Corcoran ................................................... 14 Andrea I. McClatchey .......................................... 64 Shawn Demehri .................................................. 16 David T. Miyamoto .............................................. 66 Nicholas Dyson ................................................... 18 Raul Mostoslavsky .............................................. 68 Andrew Elia ........................................................ 20 Mo Motamedi ..................................................... 70 Leif Ellisen ......................................................... 22 Christopher J. Ott ............................................... 72 David E. Fisher ................................................... 24 Shiv Pillai ............................................................ 74 Gad Getz ............................................................. 26 Luca Pinello ........................................................ 76 Timothy A. Graubert ........................................... 28 Esther Rheinbay ................................................. 78 Wilhelm Haas ..................................................... 30 Miguel N. Rivera ................................................. 80 Daniel A. Haber .................................................. 32 Dennis Sgroi ....................................................... 82 Nir Hacohen ....................................................... 34 Toshihiro Shioda ................................................. 84 Aaron Hata ......................................................... 36 David Spriggs ..................................................... 86 Konrad Hochedlinger ......................................... 38 Shannon Stott ..................................................... 88 Hanno Hock ........................................................ 40 Mario L. Suvà ...................................................... 90 Jonathan G. Hoggatt .......................................... 42 David A. Sweetser ............................................... 92 A. John Iafrate .................................................... 44 David T. Ting ....................................................... 94 Othon Iliopoulos ................................................. 46 Shobha Vasudevan ............................................. 96 Russell W. Jenkins ............................................. 48 Alexandra-Chloé Villani ..................................... 98 J. Keith Joung .................................................... 50 Lee Zou .............................................................. 100 Table of Contents i Message from the Director The Center for Cancer • defining the role of Merlin/ERM proteins in Research (CCR) is the macropinocytosis and receptor signaling major hub for basic • revealing new types of human dendritic cells and translational contributing to immune responses research within the • defining the role of the histone deacetylase SIRT6 in Massachusetts General orchestrating the Warburg effect Hospital Cancer Center. • identifying mutations caused by the APOBEC The CCR includes enzyme at DNA stem-loops, as drivers of recurrent 50 primary and affiliated mutagenesis faculty members, with multidepartmental Harvard Medical School • using an RNA-based digital circulating tumor appointments, including the Departments of Medicine, cell signature to predict drug response and early dissemination in prostate cancer Pathology, Radiation Oncology, Surgery, Dermatology and Pediatrics. These scientists are pursuing every aspect • linking changes in histone methylation to the of cancer research, from exploring cancer genetics, initiation of gene amplification in cancer cells genomics, epigenetics and proteomics to developmental • targeting RET fusions that mediate resistance to biology, cell signaling, molecular therapeutics, EGFR inhibition in lung cancer immunology, metabolism, cell cycle regulation, and • defining the scale of transcriptome-wide off-target microRNA biology. We occupy over 80,000 square feet hits using CRISPR-guided DNA base editing of laboratory space in three Mass General research • creating novel CAR-T cells secreting bispecific facilities, (Charlestown Navy Yard, Simches Research antibodies to target brain tumors Building and the Jackson Building), and our laboratories include more than 500 postdoctoral fellows, graduate This year, we are delighted to introduce four new students and technicians. We host seminar series, an CCR faculty members: Esther Rheinbay, PhD (from annual symposium, and a two-day retreat which provide the Broad Institute); Liron Bar-Peled, PhD (from the opportunities for our investigators to discuss new ideas Scripps Research Institute); Russell Jenkins, MD, PhD and spark productive collaborations. (from the Dana-Farber Cancer Institute); and Robert Manguso, PhD (from the Broad Institute). These young Some of the CCR research highlights from the past year include: investigators have already made important contributions in their respective fields and will further expand and • identifying T cell markers associated with positive strengthen our bioinformatics/computational biology, response to checkpoint immunotherapy in cell biology and cancer immunology programs. melanoma • targeting ATR response to DNA replication block in Cancer immunology and immunotherapy was the main Myelodysplastic Syndrome theme of the 2019 Jonathan Kraft Prize for Excellence ii MGH Center for Cancer Research ANNUAL REPORT 2019-2020 Daniel Haber photo by Scott Eisen in Cancer Research and Symposium presented by the our research program. During the past year Andrea Mass General Center for Cancer Research. The Prize, McClatchey, PhD was appointed as the inaugural which honors an extraordinary scientist who has made incumbent of the Poitras Family Endowed Chair in seminal contributions to cancer research, was presented Oncology and David Sweetser, MD is the inaugural to Carl June, MD from the University of Pennsylvania incumbent of the Leslie Meyer and Lewis Ball Holmes for his breakthrough contributions to the field of CAR-T Chair in Genetics and Teratology. cell therapy. He exemplifies the innovative scientist Our goal for the next year is to further advance our and thoughtful mentor that this award was intended to understanding of fundamental biological processes recognize, when established in 2014 by Robert Kraft to disrupted in cancer. We will continue our focus on honor his son Jonathan’s commitment to cancer research. developing new diagnostic and therapeutic tools that can Our investigators have successfully competed
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