LUDWIG LINK | AUGUST 2020 IN THIS ISSUE LUDWIG 7 | Remembering 21 | Ask a Sam Gambhir scientist LINK Renowned scientist, A special section Ludwig Professor, mentor on COVID-19 and AUGUST 2020 and inventor dies at 57 cancer research LIFE-CHANGING SCIENCE 1 ON THE COVER The cover image of this issue derives from a Zoom “whiteboard” generated during a townhall meeting of the Ludwig New York office. Attendees were asked to paint the word or phrase each associates with the genuine achievement of diversity and inclusiveness. The activity was inspired by discussions following the death of George Floyd, which has provoked sustained protests against systemic racism in the U.S. and a broader social awakening to prejudice in its many forms. The cover incorporates a slice of the result. LUDWIG LINK | AUGUST 2020 2 LUDWIG LINK ludwigcancerresearch.org AUGUST 2020 LETTER TABLE OF CONTENTS Cancer isn’t waiting for COVID-19 to go away. Nor are Ludwig scientists. Awards and distinctions 4 For high-impact research 4 Though lockdowns imposed by For general scientific excellence 4 the pandemic have disrupted lab For linking science to human benefit 5 operations, Ludwig researchers For illuminating the dark genome 6 have been hard at work, analyzing For a stellar start 6 data, preparing papers and planning new experiments. You’ll In memoriam 7 find here a brief report on the Ludwig Scientific Insights Sanjiv Sam Gambhir 7 webinars this past quarter, which shared tips and resources Navigating the pandemic 8 on managing through the pandemic. Managing the new normal 8 The research news in this issue includes a brief on a clinical People on the move 9 trial launched by Ludwig Johns Hopkins researchers to A new scientific advisor 9 evaluate a generic blood pressure drug as a preventive News roundup 9 intervention for the deadliest consequence of COVID-19, the Diverse landscapes 9 cytokine storm. Our other features include items on, among Toward early detection 10 other things, a urine test to detect lung cancer and a new An ounce of prevention 11 CAR-T cell that can be switched on and off on demand. A nip in the bud 12 A CAR-T full of promise 12 LUDWIG LINK | AUGUST 2020 We also have some sad news in this issue: Ludwig Professor Very smart toilet 13 at Stanford Sanjiv Sam Gambhir died in July from a cancer Helpful bugs 13 Secondhand sensitivity 14 of unknown origin. A physician-scientist and an inspired Early warning system 14 inventor, Sam was also a beloved colleague, teacher and A long read 15 mentor to many. He will be missed. Bugs sting cancer 15 Traitorous targets 16 Along the usual honors and awards won by Ludwig Innate potential 16 researchers, you’ll learn a little in this issue about the Calculated odds 17 accomplished immunologist Bob Schreiber—a new member Foci for research 17 of the Ludwig Institute’s Scientific Advisory Committee. Kill switch 18 We also thought we’d ask Ludwig scientists to share their Telltale number 18 thoughts on how the pandemic is likely to influence their own An environment of resistance 19 work and cancer research and care in general. Find out what CRISPR replicas 19 Ventilatory warning 20 they said in our special Ask a scientist section. Ask a scientist 21 Happy reading! A special section on COVID-19 and cancer research 21 Rachel Reinhardt Required reading 35 Senior Vice President for Communications 3 Awards and distinctions FOR HIGH-IMPACT RESEARCH Five Ludwig scientists were named Fellows of the Academy of the American Association for Cancer Research (AACR) Class of 2020 in May. The honorees include Ludwig Oxford’s Sir Peter Ratcliffe—who was recognized for his landmark discoveries on how cells sense Peter Ratcliffe Rakesh Jain oxygen and respond to its depletion—and Ludwig Oxford Ludwig Harvard four Ludwig Harvard researchers. Rakesh Jain was recognized for his investigations of how the tumor microenvironment fuels tumor progression and confers resistance, and how anti-angiogenic therapy can normalize tumor blood vessels and improve chemo- and immunotherapies; Kornelia Polyak for dissecting the role of intratumoral heterogeneity in breast cancer and cancer metastasis; Alan D’Andrea for LUDWIG LINK | AUGUST 2020 his contributions to the field of DNA Kornelia Polyak Alan D’Andrea damage and repair, and for defining how Ludwig Harvard Ludwig Harvard such defects drive Fanconi anemia; and Myles Brown for his discoveries on the role steroid hormones and their cellular receptors play in the initiation and progression of various cancers. Election to the Academy is an honor bestowed by the AACR on those whose scientific contributions have “propelled significant innovation and progress against cancer.” Myles Brown Ludwig Harvard 4 Awards and distinctions FOR GENERAL FOR LINKING SCIENCE SCIENTIFIC EXCELLENCE TO HUMAN BENEFIT In April, Ludwig Oxford Director Xin Lu Ludwig Harvard Co-director George was elected to the Fellowship of the Demetri was named the recipient of the Royal Society. Xin was recognized by the 2020 David A. Karnofsky Award in April. Royal Society for her contributions to He will deliver the Karnofsky Lecture at our understanding of cancer cell biology, the virtual ASCO meeting in August 2020. particularly her work on the regulation Among the most prestigious honors of p53, a tumor suppressor protein bestowed by the American Society of whose inactivation or mutation aids the Xin Lu Clinical Oncology, the Karnofsky Award progression of a wide variety of cancers. Ludwig Oxford recognizes outstanding contributions She is perhaps best known for leading the to cancer research, diagnosis and discovery and functional characterization treatment. George has made major of the ASPP family of proteins, which contributions to our understanding and control p53 activity. Aside from opening treatment of cancers that arise in the new approaches to selectively killing soft tissue and bone, known as sarcomas. cancer cells, Xin’s continuing exploration His development of selective inhibitors of those proteins has exposed their role of the mutated KIT oncogene led in 2002 in other disorders, including sudden to historic approval of the first targeted cardiac death and brain abnormalities. therapy, imatinib, for gastrointestinal Xin has directed Ludwig’s Oxford Branch stromal tumors (GISTs), the most common LUDWIG LINK | AUGUST 2020 since it was established in 2007 and is sarcoma. Imatinib was initially developed a Professor in the Nuffield Department to inhibit the fusion oncoprotein, BCR- of Medicine at the University of Oxford, George Demetri ABL, in chronic myeloid leukemia; GIST a Fellow of the Academy of Medical Ludwig Harvard was the second approval. With George’s Sciences and the Royal Society of Biology, collaboration, the drug has also been a Fellow by election of the Royal College approved for DFSP, a different sarcoma of Pathologists and a member of the driven by a PDGF-gene fusion and other European Molecular Biology Organization. blood cancers. George’s subsequent Founded in 1660, the Royal Society is a research led to the approval of second storied fellowship of eminent scientists, and third generation treatments for GISTs, engineers and technologists in the UK as well as treatments for other sarcomas. and the Commonwealth whose mission His work has influenced the development is to “recognize, promote, and support of drugs for a wide range of malignancies, excellence in science and to encourage including the recent inhibitors of the development and use of science for oncogenic TRK-fusions in rare subsets of the benefit of humanity.” virtually all cancers. 5 Awards and distinctions FOR ILLUMINATING THE DARK GENOME Ludwig Stanford Professor Howard Chang positional identity—work that led to his was elected to the National Academy lab’s discovery of a sprawling family of of Sciences (NAS) and the American genes encoding long noncoding RNAs Academy of Arts and Sciences (AAAS) that regulate gene activity and play in April. Howard’s lab has developed critical roles in an array of biological powerful new technologies to explore processes, including cancer. Established how the large expanses of the genome in 1780, the AAAS honors excellence and that encode no proteins—98% of seeks “to cultivate every art and science Howard Chang the whole—control the expression which may tend to advance the interest, Ludwig Stanford of the remaining 2%. Applying these honor, dignity, and happiness of a free, technologies, Howard and his colleagues independent, and virtuous people.” The have made transformative discoveries on NAS was established in 1863 and charged how regulatory DNA sequences in these with providing independent, objective regions influence biological phenomena advice to the nation on matters related ranging from embryonic development to science and technology. Election to to aging to the genesis of cancers. the NAS is considered one of the highest Howard has also explored how cells of honors a scientist can receive. the body establish and maintain their LUDWIG LINK | AUGUST 2020 FOR A STELLAR START In May, Ludwig Johns Hopkins researcher odds for a cure. Jonathan also received Jonathan Dudley was named a winner this year’s Benjamin Castleman Award of this year’s prestigious Damon Runyon from the United States and Canadian Physician-Scientist Training Award for Academy of Pathology at its national his work on a new approach to screening conference. The award is given to one for bladder, endometrial and ovarian pathologist under forty each year for an cancers. A board-certified pathologist, outstanding paper in the field of human Jonathan is developing a way to detect pathology. Jonathan was recognized for Jonathan Dudley cells in urine and pap smears that have work he initiated during his residency Ludwig Johns Hopkins abnormal amounts of DNA, or aneuploidy. and fellowship with Ludwig Stanford Aneuploidy is present in over 90% of investigators Maximilian Diehn and Ash cancers, but is difficult to detect with Alizadeh creating a method to detect traditional liquid biopsy methods in the bladder cancer from cell-free DNA in urine early stages of tumor growth.