3Rd Joint Meeting of BSA and NCAB
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Tyler Jacks, Phd President, Break Through Cancer; Founding Director, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
Tyler Jacks, PhD President, Break Through Cancer; Founding Director, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology www.breakthroughcancer.org Dr. Tyler Jacks, the President of Break Through Can- Dr. Jacks is an elected member of the National Acad- cer, has dedicated his life to cancer research. He emy of Sciences, the National Academy of Medicine, is the Founding Director of the Koch Institute for the American Academy of Arts and Sciences, and Integrative Cancer Research at the Massachusetts was a member of the inaugural class of Fellows of Institute of Technology, the David H. Koch Profes- the AACR Academy. In 2015, Dr. Jacks received the sor of Biology, and Co-director of the Ludwig Cen- Killian Faculty Achievement Award, the highest honor ter for Molecular Oncology. From 2001 – 2007, he the MIT faculty can bestow upon one of its members. served as director of the Koch Institute’s predeces- In 2016, Dr. Jacks co-chaired the Blue-Ribbon Panel sor, the MIT Center for Cancer Research, and was for (then) Vice President Joe Biden’s Cancer Moon- a long-standing Investigator of the Howard Hughes shot Initiative. He was also chair of the National Medical Institute (1994-2021). Dr. Jacks received his Cancer Advisory Board of the National Cancer Insti- bachelor’s degree in Biology from Harvard College, tute during the Obama administration. and his doctorate from the University of California, Dr. Jacks serves on the Board of San Francisco, where he trained with Nobel Laure- Directors of Amgen and Thermo ate Harold Varmus. He was a postdoctoral fellow Fisher Scientific. -
Francisco J. Sánchez-Rivera
Francisco J. Sánchez-Rivera Memorial Sloan Kettering Cancer Center Sloan Kettering Institute Zuckerman Research Building 417 East 68th Street - Z-1119 New York, NY 10065 Tel: 939-292-5555 E-mail: [email protected] Education Fall 2008 - Winter 2016 Massachusetts Institute of Technology Department of Biology Ph.D. in Biology Fall 2003 - Spring 2008 University of Puerto Rico, Mayagüez, PR Department of Biology B.S. in Microbiology Research January 2016 - Present Memorial Sloan Kettering Cancer Center - Sloan Kettering Institute Postdoctoral fellow in the laboratory of Dr. Scott W. Lowe Main Project: Dissecting the biological impact of mutational heterogeneity using mouse models and genome engineering June 2009 - January 2016 Department of Biology at MIT and David H. Koch Institute for Integrative Cancer Research Graduate student in the laboratory of Dr. Tyler Jacks Thesis title: Constructing and deconstructing cancer using CRISPR-Cas9 Main projects: 1) Modeling cancer in vivo using the CRISPR-Cas9 system. 2) CRISPR screens for uncovering genotype-specific cancer drug targets. 3) Molecular mechanisms dictating tumor-specific responses to p53 restoration. June 2008 - August 2008 Whitehead Institute for Biomedical Research Summer student researcher in the laboratory of Dr. Harvey F. Lodish Project: The role of histone deacetylases in enucleation of cultured mouse fetal erythroblasts. June 2007 - August 2007 Department of Biology at MIT Summer student researcher in the laboratory of Dr. Stephen P. Bell Project: Identification of dominant negative helicase mutants by insertional mutagenesis of the yeast replicative helicase Mcm2-7. January 2006 - May 2008 University of Puerto Rico, Mayagüez Campus Department of Biology Undergraduate researcher in the laboratory of Dr. -
The Role of HIF-1Α in Sarcoma Metastasis and Response to Radiation Therapy
The Role of HIF-1α in Sarcoma Metastasis and Response to Radiation Therapy by Minsi Zhang Department of Pharmacology and Cancer Biology Duke University Date:_______________________ Approved: ___________________________ David Kirsch, Supervisor ___________________________ Mark Dewhirst ___________________________ Christopher Kontos ___________________________ Kenneth Poss ___________________________ Jeffrey Rathmell Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Pharmacology and Cancer Biology in the Graduate School of Duke University 2015 ABSTRACT The Role of HIF-1α in Sarcoma Metastasis and Response to Radiation Therapy by Minsi Zhang Department of Pharmacology and Cancer Biology Duke University Date:_______________________ Approved: ___________________________ David Kirsch, Supervisor ___________________________ Mark Dewhirst ___________________________ Christopher Kontos ___________________________ Kenneth Poss ___________________________ Jeffrey Rathmell An abstract of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Pharmacology and Cancer Biology in the Graduate School of Duke University 2015 Copyright by Minsi Zhang 2015 Abstract The degree of intratumoral hypoxia is clinically correlated to poor response to therapy and increased incidence of distal spread in various cancer subtypes. Specifically, the transcription factor Hypoxia Inducible Factor-1α (HIF- 1α), which is accumulated in cells in response to a hypoxic microenvironment, is implicated in poor disease outcome associated with intratumoral hypoxia. Using novel genetically engineered mouse models of primary soft tissue sarcoma, I show that in vivo genetic deletion of HIF-1α specifically in tumor cells 1) decreases the incidence of lung metastases by limiting sarcoma collagen deposition, and 2) improves sarcoma response to radiation therapy by limiting the inflammatory response and metabolic adaptations. -
Susceptibility to Astrocytoma in Mice Mutant for Nf1 and Trp53 Is Linked to Chromosome 11 and Subject to Epigenetic Effects
Susceptibility to astrocytoma in mice mutant for Nf1 and Trp53 is linked to chromosome 11 and subject to epigenetic effects Karlyne M. Reilly*†, Robert G. Tuskan*, Emily Christy‡§, Dagan A. Loisel‡§, Jeremy Ledger‡, Roderick T. Bronson¶, C. Dahlem Smithʈ, Shirley Tsang**, David J. Munroe**, and Tyler Jacks‡§ *Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD 21702; ‡Department of Biology and Center for Cancer Research and §Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02169; ¶Department of Pathology, Harvard Medical School, Boston, MA 02115; and Laboratories of ʈAnimal Sciences Program and **Molecular Technology, Science Applications International Corporation, Frederick, MD 21702 Edited by Bert Vogelstein, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, and approved July 9, 2004 (received for review February 21, 2004) Astrocytoma is the most common malignant brain tumor in hu- tumors such as astrocytoma (8, 9), although this observation is mans. Loss of the p53 signaling pathway and up-regulation of the as likely due to the particular mutant allele of NF1 (10) as to ras signaling pathway are common during tumor progression. We genetic or environmental risk factors. Astrocytomas are also have shown previously that mice mutant for Trp53 and Nf1 frequently associated with mutations in Tp53 in sporadic cases develop astrocytoma, progressing to glioblastoma, on a C57BL͞6J (11, 12) or in LFS patients carrying germline mutations in the strain background. In contrast, here we present data that mice Tp53 gene (5) (Trp53 in the mouse). Although there are no clear mutant for Trp53 and Nf1 on a 129S4͞SvJae background are highly data in patients that genetic background affects the risk of resistant to developing astrocytoma. -
The David H. Koch Institute for Integrative Cancer Research at MIT
The David H. Koch Institute for Integrative Cancer Research at MIT The David H. Koch Institute for Integrative Cancer Research was announced on October 9, 2007. By combining the faculty of the (now former) MIT Center for Cancer Research (CCR) with an equivalent number of distinguished engineers drawn from various MIT departments, the Koch Institute will continue CCR’s tradition of scientific excellence while also seeking to directly promote innovative ways to diagnose, monitor, and treat cancer through advanced technology. Among the engineering faculty there will be remarkable diversity, as the Electrical Engineering and Computer Science, Materials Science and Engineering, Biological Engineering, Chemical Engineering, and Mechanical Engineering departments will be represented in the Koch Institute. For three decades, CCR has been a mainstay of MIT’s—and the nation’s—efforts to conquer cancer. Its faculty has included five Nobel Prize winners, and the wealth of fundamental discoveries that have emerged under its aegis have helped shape the face of molecular biology. Under the banner of the Koch Institute, the future promises to hold even more astounding advances. Within the Koch Institute we will not directly provide clinical care for cancer patients but discoveries made by Koch Institute scientists and engineers will have a broad impact on how the disease is detected and managed. Applying our great strengths in science and technology, and working closely with our clinical collaborators, Koch Institute researchers will be tireless in unraveling the complexities of this disease and bringing new discoveries—and new hope—to patients. The Koch Institute includes more than 40 laboratories and more than 500 researchers located at our headquarters and across the MIT campus. -
Conference Program and Schedule
02_BCR_front.qxd:Layout 1 9/15/09 2:23 PM Page 11 Conference Program and Schedule Thursday, October 8, 2009 1:30 p.m.-3:45 p.m. Session 2: Mouse Models of Cancer Imperial Ballroom 8:00 a.m.-9:00 a.m. Continental Breakfast Chairperson: Guillermina Lozano, UT M. D. Anderson Stanbro Room Cancer Center, Houston, TX The regulation of p53 tumor suppressing activities* Guillermina Lozano 9:00 a.m.-12:00 p.m. Session 1: Genes and Pathways in Cancer Studying tumor evolution in mouse models of cancer* Imperial Ballroom Tyler Jacks, David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA Chairperson: Robert A. Weinberg, Whitehead Institute for Biomedical Research, Cambridge, MA Dissecting tumor suppressor gene networks in vivo* Scott W. Lowe, Cold Spring Harbor Laboratory, Molecular characterization of circulating tumor cells Cold Spring Harbor, NY Daniel A. Haber, Massachusetts General Hospital, Charlestown, MA From chromosome engineering to chromatin remodeler: 3:45 p.m.-4:30 p.m. Special Lecture: CHD5 is a tumor suppressor mapping to human 1p36* Host-Germline Genetics Alea A. Mills, Cold Spring Harbor Laboratory, Imperial Ballroom Cold Spring Harbor, NY Single nucleotide polymorphisms in the p53 pathway* New cancer targets emerging from studies of the VHL tumor Arnold J. Levine, Institute for Advanced Study, Princeton, NJ suppressor gene William G. Kaelin, Jr., Dana-Farber Cancer Institute, Boston, MA 4:30 p.m.-4:45 p.m. Coffee Break PI3-Kinase and cancer metabolism* Stanbro Room Lewis C. Cantley, Beth Israel Deaconess Medical Center, Boston, MA 4:45 p.m.-5:30 p.m. -
Development and Characterization of Immunogenic Genetically Engineered Mouse Models of Pancreatic Cancer
Development and characterization of immunogenic genetically engineered mouse models of pancreatic cancer By Laurens J. Lambert MSc, Medical Biology Radboud University, 2014 Submitted to the Department of Biology in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy at the MASSACHUSETTS INSTITUTE OF TECHNOLOGY September 2020 © 2020 Massachusetts Institute of Technology. All rights reserved. Signature of Author………………………………………………………………………………. Laurens J. Lambert Department of Biology June 16, 2020 Certified by………..………………………………………………………………………………. Tyler Jacks David H. Koch Professor of Biology Investigator, Howard Hughes Medical Institute Thesis Supervisor Accepted by………………………………………………………………………………………. Stephen Bell Uncas and Helen Whitaker Professor of Biology Investigator, Howard Hughes Medical Institute Co-Director, Biology Graduate Committee 2 Development and characterization of immunogenic genetically engineered mouse models of pancreatic cancer By Laurens J. Lambert Submitted to the Department of Biology on June 16, 2020 in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Biology Abstract Insights into mechanisms of immune escape have fueled the clinical success of immunotherapy in many cancers. However, pancreatic cancer has remained largely refractory to checkpoint immunotherapy. To uncover mechanisms of immune escape, we have characterized two preclinical models of immunogenic pancreatic ductal adenocarcinoma (PDAC). In order to dissect the endogenous antigen-specific T cell response in PDAC, lentivirus encoding the Cre recombinase and a tumor specific antigen LSL-G12D/+; flox/flox (SIINFEKL, OVA257-264) was delivered to Kras Trp53 (KP) mice. We demonstrate that KP tumors show distinct antigenic outcomes: a subset of PDAC tumors undergoes clearance or editing by a robust antigen-specific CD8+ T cell response, while a fraction undergo immune escape. -
Biographical Memoirs
National Academy of Sciences - Biographical Memoirs http://www.nasonline.org/publications/biographical-memoirs/online-collection.html By Michael P. Filosa Flack Norris (1871-1940) for the November Nucleus, I came across his biographical memoir on the website of the National Academy of Sciences (NAS). This memoir was written by John D. Roberts and was presented to the Academy in 1974, a scant(!) 34 years after his death. The NAS was founded in 1863 by 50 of the most prominent scientists in the United States, and its initial charter was signed by Abraham Lincoln. It is a tradition that each of its members be memorialized in a memoir to the Academy written by a peer (or two). These memoirs are a treasure trove of the history of science. The sole weakness is that they are posthumous and not necessarily, very timely. However, they are quite thorough and a good overview of the scientists, complete with a detailed listing of their major works. During my school years, I was always intrigued with stories about great scientists. Dan Kemp would talk extensively about his thesis advisor, R. B. Woodward, and his works. Those stories about Woodward (1917-1979) and also Gilbert Stork were very influential in my decision to pursue synthetic organic chemistry as a career. Woodward’s memoir was written by Elkan Blout (with assistance from Frank Westheimer) and was published in 2001, a “scant” 22 years after his death. The memoirs are often glowing: “Robert Burns Woodward was the preeminent organic chemist of the twentieth century. This opinion is shared by his colleagues, students and by other distinguished chemists.” Blout includes lengthy commentaries from Sir Derek Barton, Roald Hoffman and Albert Eschenmoser in the memoir. -
Ras Activation in Astrocytomas and Neurofibromas
REVIEW ARTICLE Ras Activation in Astrocytomas and Neurofibromas Abhijit Guha ABSTRACT: Oncogenic mutations resulting in activated Ras Guanosine Triphosphate (GTP) are preva lent in 30% of all human cancers, but not primary nervous system tumors. Several growth factors/recep tors are implicated in the pathogenesis of malignant astrocytomas including epidermal growth factor (EGFR) and platelet derived growth factor (PDGF-R) receptors, plus the highly potent and specific angio genic vascular endothelial growth factor (VEGF). A significant proportion of these tumors also express a truncated EGFR, which is constitutively activated. Our work demonstrates that the mitogenic signals from both the normal PDGF-R and EGFR and the truncated EGFR activate Ras. Inhibition of Ras by genetic or pharmacological strategies leads to decreased astrocytoma tumorgenic growth in vitro and decreased expression of VEGF. This suggests that these agents may be potentially important as novel anti-proliferative and anti-angiogenic therapies for human malignant astrocytomas. In contrast to astrocytomas, where increased levels of activated Ras GTP results from transmitted sig nals from activated growth factor receptors, the loss of neurofibromin is postulated to lead to functional up-regulation of the Ras pathway in neurofibromatosis-l(NF-l). We have demonstrated that NF-1 neu rofibromas and neurogenic sarcomas, compared to non-NF-1 Schwannomas, have markedly elevated lev els of activated Ras GTP. Increased Ras GTP was associated with increased tumor vascularity in the NF-1 neurogenic sarcomas, perhaps related to increased VEGF secretion. The role of Ras inhibitors as potential therapy in this tumor is also under study. RESUME: Activation de Ras dans les astrocytomes et les neurofibromes (medaille du College Royal en Chirurgie, 1997). -
Entire Annual Report (PDF
WELCOME From the Chair, Mary Lowe Good cience and technology are key to the welfare of our global village. In 2001, we were reminded again of the importance of research to the well-being Sof people everywhere. Forensic genomics, chemical analysis, and other such pursuits—once arcane to all but specialists—became familiar to a larger audience, as news of efforts to understand tragedy reached us through newspapers, televisions, radios and the Internet. Scientific discussion, confined to Victorian-era parlors since the days of Darwinian debate, claimed a more central location on our cultural stage. As the public’s perception of and appreciation for science and technology changes, the AAAS and its membership are preparing to take on a larger leadership role on behalf of science and its applications. The new AAAS rallying cry, “Advancing science • Serving society,” reflects a desire to build more and better bridges between policymakers, scientists, educators, and the average citizen. After all, the population keeps growing while 2001 farmland disappears, and we’re living longer than ever before, demanding better shelter, education, health care, and sanitation. Improved quality of life also requires answers to fundamental mysteries—from our cosmic origins, to our REPORT social and geographic paths as we peopled the Earth. In 2001, basic and applied research delivered practical advances and esoteric knowledge alike: Molecule-sized circuits— ANNUAL so small that billions could fit on today’s computer chips—were named the year’s top scientific achievement, promising 1 computers that translate conversations on the fly, or solve climate-change riddles in a snap. -
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Re-programming Immunity Against Glioblastoma via RNA Nanoparticle Vaccines by Elias Joseph Sayour Department of Pathology Duke University Date:_______________________ Approved: ___________________________ Duane Mitchell, Supervisor ___________________________ Soman Abraham ___________________________ Matthias Gromeier ___________________________ Oren Becher ___________________________ Salvatore Pizzo, Chair Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Pathology in the Graduate School of Duke University 2015 i v ABSTRACT Re-programming Immunity Against Glioblastoma via RNA Nanoparticle Vaccines by Elias Joseph Sayour Department of Pathology Duke University Date:_______________________ Approved: ___________________________ Duane Mitchell, Supervisor ___________________________ Soman Abraham ___________________________ Matthias Gromeier ___________________________ Oren Becher ___________________________ Salvatore Pizzo, Chair An abstract of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Pathology in the Graduate School of Duke University 2015 Copyright by Elias Joseph Sayour 2015 Abstract Despite aggressive surgical resection, cytotoxic chemotherapy, and external beam radiotherapy, most cases of glioblastoma (GBM) remain recalcitrant. These outcomes necessitate novel developmental therapeutics that spare normal tissue. Immunotherapy is a promising novel adjuvant treatment that can -
Statement of Dr. Tyler Jacks, Phd Director, Koch Institute For
Statement of Dr. Tyler Jacks, PhD Director, Koch Institute for Integrative Cancer Research at MIT Before The United States House of Representatives Committee on Oversight and Government Reform For the Hearing entitled: Federally Funded Cancer Research: Coordination and Innovation March 29, 2017 Chairman Chaffetz, Ranking Member Cummings and other members of the Committee, thank you for the opportunity to appear before you to discuss the state of cancer research in our country today and the transformation in cancer care that we are witnessing owing to the federal investment in our understanding and treatment of this disease over the past four decades. My name is Tyler Jacks, and I am the Director of the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (MIT), a National Cancer Institute (NCI)-designated Cancer Center. I was previously the Chairman of the National Cancer Advisory Board, and I have served as President of the American Association of Cancer Research (AACR). I am also a member of the Board of Directors of Amgen and Thermo Fisher Scientific. I have been actively participating in cancer research for the past 36 years, including overseeing a research laboratory at MIT currently focused on cancer genetics and immuno- oncology. I am not here as a representative of MIT nor as a representative of the NCI but as an experienced cancer researcher. Along with my colleagues, Dr. Elizabeth Jaffee, who is also testifying today, and Dr. Dinah Singer, Acting Deputy Director of the NCI, I co-chaired the Cancer Moonshot Blue Ribbon Panel. This Panel was charged in the spring of 2016 by President Obama and Vice President Biden to establish the research agenda for the Cancer Moonshot.