Akhilesh Pandey, M.D., Ph.D. Associate Professor Institute Of
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Department of Biology, Report to the President 2016-2017
Department of Biology Academic year 2016–2017 was exciting and productive for the Department of Biology. The department is considered one of the best biological science departments in the world. Our superb faculty members are leaders in biological research and education. Some of the news regarding our faculty, research, and educational programs is highlighted below. Faculty Count and Departures During AY2017, the Department of Biology had 56 faculty members: 44 full professors, eight associate professors, and four assistant professors. Research homes are distributed among Building 68, the Broad Institute, the Koch Institute for Integrative Cancer Research, the Picower Institute for Learning and Memory, and the Whitehead Institute for Biomedical Research. In addition to 56 primary faculty members, there were six faculty members with secondary appointments in Biology. These joint faculty members provide important connections to other departments, including Brain and Cognitive Sciences, Chemistry, Biological Engineering, and Civil and Environmental Engineering. We are saddened by the loss of Professor Susan Lindquist, who passed away in October 2016. Hidde Ploegh (Whitehead Institute) moved to Children’s Hospital in January 2017. Professor William (Chip) Quinn (Biology/Brain and Cognitive Sciences) retired in July 2016. Faculty Awards Department of Biology faculty members are widely recognized for their contributions to the field. Among our core faculty are three Nobel Laureates, 30 members of the National Academy of Sciences, 28 members of the American Academy of Arts and Sciences, 14 fellows of the American Association for the Advancement of Science, four recipients of the National Science Foundation National Medal of Science, and 15 Howard Hughes Medical Institute (HHMI) investigators. -
ANNUAL REPORT 2019 1 Contents Director’S Letter 1
Whitehead Institute ANNUAL REPORT 2019 1 Contents Director’s Letter 1 Chair’s Letter 3 Members & Fellows 4–5 Science 6 Community 44 Philanthropy 56 2 The Changing Face of Discovery For 37 years, Whitehead Institute has demonstrated an ability to drive scientific discovery and to chart paths into new frontiers of knowledge. Its continuing achievements are due, in substan- tial part, to the unique capacities and dedication of Members who joined the Institute in the 1980s and ‘90s — from Founding Members Gerald Fink, Harvey Lodish, Rudolf Jaenisch, and Robert Weinberg to those who followed, including David Bartel, David Sabatini, Hazel Sive, Terry Orr-Weaver, Richard Young, and me. Those long-serving Members continue to do pioneering science and to be committed teachers and mentors. Yet we have begun an inevitable genera- tional transition: In the last two years, Gerry and Terry have closed their labs, and Harvey will do so this coming year. The exigencies of time mean that, increasingly, Whitehead Institute’s ability to maintain its vigorous scientific leadership depends on our next generation of researchers. As I move toward the conclusion of my term as director, I am particularly proud of the seven current Members and the 14 Whitehead Institute Fellows we recruited during the last 16 years. The newest of those stellar researchers joined us in 2019: Whitehead Institute Member Pulin Li and Whitehead Fellow Kipp Weiskopf. Pulin studies how circuits of interacting genes in individu- al cells enable multicellular functions, such as self-organizing into complex tissues, and her research brilliantly combines approaches from synthetic biology, developmental and stem cell biology, biophysics, and bioengineering to study these multicellular behaviors. -
DC Welcomes ASBMB APRIL 28–MAY 2
ASBMB ANNUAL MEETING PULLOUT GUIDE INSIDE April 2007 DC Welcomes ASBMB APRIL 28–MAY 2 American Society for Biochemistry and Molecular Biology Scientists helping scientists… It costs no more to choose the very best for your custom peptides and antibodies… Ac-C T P R Q I pS F N F K-OH ◆ All peptides are made in our laboratories 1461.640 with the most rigorous QC in the industry – pSFNFK-H3PO4 -98 623.245 We sequence every purified -H3PO4 peptide we manufacture! ◆ PhD scientists with over 70 years of 623.0 626.5 combined experience in Chemistry, Mass 293.141 2 Cell Biology and Immunology 1218.599 1169.510 1347.658 536.784 740.405 809.426 1317.591 246.072 499.227 972.531 400 600 800 1000 1200 1400 Mass ◆ Complete antibody protocols and no hidden charges. Phosphospecific antibody experts! ◆ Custom peptides up to 100 AAs in length and at purities up to >98%. Peptides for epitope mapping as low as $4/AA. ◆ Modifications include phosphorylated amino acids, dye-labeling, cyclic peptides, and peptides with stable isotopes. Experience for yourself why research scientists around the world trust 21st Century Biochemicals for their custom peptides and antibodies! Come speak with our scientists at: Experimental Biology, Washington, DC - Booth 130 Apr. 28 – May 2 ARVO, Association for Research in Vision & Ophthalmology, Ft. Lauderdale, FL - Booth 102 May 6 – 9 The American Association of Immunologists, Miami Beach, FL - Booth 427 May 18 – May 22 www.21stcenturybio.com 33 Locke Drive, Marlboro, MA 01752 Made in the P: 508.303.8222 Toll-free: 877.217.8238 U.S.A. -
Caspase-8 and RIP Kinases Regulate Bacteria-Induced Innate Immune Responses and Cell Death
Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death Dan Wenga, Robyn Marty-Roixa, Sandhya Ganesana, Megan K. Proulxb, Gregory I. Vladimera, William J. Kaiserc, Edward S. Mocarskic, Kimberly Pouliota, Francis Ka-Ming Chand, Michelle A. Kellihere, Phillip A. Harrisf, John Bertinf, Peter J. Goughf, Dmitry M. Shayakhmetovg, Jon D. Goguenb, Katherine A. Fitzgeralda,h, Neal Silvermana, and Egil Liena,h,1 aProgram in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine, bDepartment of Microbiology and Physiological Systems, dDepartment of Cancer Biology, and eDepartment of Pathology, University of Massachusetts Medical School, Worcester, MA 01605; cDepartment of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322; fPattern Recognition Receptor Discovery Performance Unit, Immuno-inflammation Therapeutic Area, GlaxoSmithKline, Collegeville, PA 19426; gLowance Center for Human Immunology, Departments of Pediatrics and Medicine, Emory University, Atlanta, GA 30322; and hCentre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway Edited by Ruslan Medzhitov, Yale University School of Medicine, New Haven, CT, and approved April 1, 2014 (received for review February 25, 2014) A number of pathogens cause host cell death upon infection, and Yersinia outer protein J (YopJ; YopP in Yersinia enterocolitica), al- Yersinia pestis, infamous for its role in large pandemics such as the though it is unclear whether this is entirely by apoptosis (11, 12). All “Black Death” in medieval Europe, induces considerable cytotoxic- human-pathogenic Yersiniae (Y. pestis, Yersinia pseudotuberculosis, ity. The rapid killing of macrophages induced by Y. -
Harvey Lodish, Phd Professor Biology and Professor of Bioengineering
Harvey Lodish, PhD Professor Biology and Professor of Bioengineering Academic Entrepreneurs, New Technologies, and Building a Biotechnology Ecosystem: A Personal History A leader in the field of molecular and cellular biology, Dr. Harvey F. Lodish has isolated and cloned numerous surface membrane proteins that play a role in blood development, cell signaling, glucose transport, and lipid metabolism. He earned his PhD at the Rockefeller University in 1966. A Founding Member of the Whitehead Institute, Dr. Lodish joined the MIT faculty in 1968 and has been a professor of biology since 1976 and professor of biological engineering since 1999. Dr. Lodish is also the lead author of the widely used textbook Molecular Cell Biology. The book has been translated into 14 languages and the ninth edition appeared in January, 2021. He is a Member of the National Academy of Sciences, a Fellow of the American Association for the Advancement of Science, the American Academy of Arts and Sciences, and the American Academy of Microbiology, and an Associate (Foreign) Member of the European Molecular Biology Organization. He received the 2010 Mentoring Award from the American Society of Hematology, the 2016 American Society for Cell Biology WICB Sandra K. Masur Senior Leadership Mentoring Award, the 2016 Pioneer Award from the Diamond Blackfan Anemia Foundation, and the Metcalf Lifetime Achievement Award from the International Society for Experimental Hematology in 2020. Dr. Lodish is a member of the Board of Trustees of Children’s Hospital, Boston, where he was Chair of the Research Committee of the Board of Trustees. From 2007 - 2014 he was Founding Chair of the Scientific Advisory Board of the Massachusetts Life Sciences Center, the group charged with oversight of the state’s 10- year $1 billion investment in the life sciences. -
Fire Departments of Pathology and Genetics, Stanford University School of Medicine, 300 Pasteur Drive, Room L235, Stanford, CA 94305-5324, USA
GENE SILENCING BY DOUBLE STRANDED RNA Nobel Lecture, December 8, 2006 by Andrew Z. Fire Departments of Pathology and Genetics, Stanford University School of Medicine, 300 Pasteur Drive, Room L235, Stanford, CA 94305-5324, USA. I would like to thank the Nobel Assembly of the Karolinska Institutet for the opportunity to describe some recent work on RNA-triggered gene silencing. First a few disclaimers, however. Telling the full story of gene silencing would be a mammoth enterprise that would take me many years to write and would take you well into the night to read. So we’ll need to abbreviate the story more than a little. Second (and as you will see) we are only in the dawn of our knowledge; so consider the following to be primer... the best we could do as of December 8th, 2006. And third, please understand that the story that I am telling represents the work of several generations of biologists, chemists, and many shades in between. I’m pleased and proud that work from my labo- ratory has contributed to the field, and that this has led to my being chosen as one of the messengers to relay the story in this forum. At the same time, I hope that there will be no confusion of equating our modest contributions with those of the much grander RNAi enterprise. DOUBLE STRANDED RNA AS A BIOLOGICAL ALARM SIGNAL These disclaimers in hand, the story can now start with a biography of the first main character. Double stranded RNA is probably as old (or almost as old) as life on earth. -
AIM2 and NLRC4 Inflammasomes Contribute with ASC to Acute Brain Injury Independently of NLRP3
AIM2 and NLRC4 inflammasomes contribute with ASC to acute brain injury independently of NLRP3 Adam Denesa,b,1, Graham Couttsb, Nikolett Lénárta, Sheena M. Cruickshankb, Pablo Pelegrinb,c, Joanne Skinnerb, Nancy Rothwellb, Stuart M. Allanb, and David Broughb,1 aLaboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, Budapest, 1083, Hungary; bFaculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom; and cInflammation and Experimental Surgery Unit, CIBERehd (Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas), Murcia Biohealth Research Institute–Arrixaca, University Hospital Virgen de la Arrixaca, 30120 Murcia, Spain Edited by Vishva M. Dixit, Genentech, San Francisco, CA, and approved February 19, 2015 (received for review November 18, 2014) Inflammation that contributes to acute cerebrovascular disease is or DAMPs, it recruits ASC, which in turn recruits caspase-1, driven by the proinflammatory cytokine interleukin-1 and is known causing its activation. Caspase-1 then processes pro–IL-1β to a to exacerbate resulting injury. The activity of interleukin-1 is regu- mature form that is rapidly secreted from the cell (5). The ac- lated by multimolecular protein complexes called inflammasomes. tivation of caspase-1 can also cause cell death (6). There are multiple potential inflammasomes activated in diverse A number of inflammasome-forming PRRs have been iden- diseases, yet the nature of the inflammasomes involved in brain tified, including NLR family, pyrin domain containing 1 (NLRP1); injury is currently unknown. Here, using a rodent model of stroke, NLRP3; NLRP6; NLRP7; NLRP12; NLR family, CARD domain we show that the NLRC4 (NLR family, CARD domain containing 4) containing 4 (NLRC4); AIM 2 (absent in melanoma 2); IFI16; and AIM2 (absent in melanoma 2) inflammasomes contribute to and RIG-I (5). -
Sulindac Sulfide-Induced Apoptosis Involves Death Receptor 5 and the Caspase 8-Dependent Pathway in Human Colon and Prostate Cancer Cells1
[CANCER RESEARCH 61, 6918–6924, September 15, 2001] Sulindac Sulfide-induced Apoptosis Involves Death Receptor 5 and the Caspase 8-dependent Pathway in Human Colon and Prostate Cancer Cells1 Ying Huang, Qin He, Michael J. Hillman, Rong Rong, and M. Saeed Sheikh2 Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, New York 13210 ABSTRACT which the NSAIDs mediate their chemopreventive and antitumori- genic effects remain less well understood but may be multifaceted in Sulindac is the most extensively investigated clinically relevant chemo- nature. Evidence suggests that the chemopreventive effects of preventive nonsteroidal anti-inflammatory drug. Sulindac sulfide is one of NSAIDs could be attributed to their apoptosis-inducing potential. For the major metabolites of sulindac that is believed to mediate its antitu- morigenic effects by inducing apoptosis. Recent evidence suggests that example, sulindac is the most extensively investigated clinically rel- sulindac sulfide engages the mitochondrial pathway involving caspase 9 evant chemopreventive NSAID that reduces the number and size of and Bax to mediate its apoptotic effects [Zhang et al., Science (Wash. DC), the colorectal tumors in genetically susceptible humans and animals 290: 989–992, 2000]. In this report, we demonstrate that sulindac sulfide (5–7). Sulindac sulfide and sulindac sulfone are the two major me- also engaged the membrane death receptor (DR) pathway to mediate tabolites of sulindac; sulindac sulfide is COX selective, whereas apoptosis. Sulindac sulfide up-regulated DR5 and activated the proximal sulindac sulfone is believed to lack COX-inhibitory activity (8). Both caspase 8 in various different colon and prostate cancer cell lines. -
Curiosity, Cell Death and Caspases: One Researcher’S Journey to Big Discoveries
Health & Medicine ︱ Professor Vishva Dixit Curiosity, cell death and caspases: One researcher’s journey to big discoveries All comic book superheroes have isii, Kenya, the mid-1950s. Valley, and at the heart of the African tea an intriguing ‘origins story’; and The East African country is still industry. Nestled in the mountains 7000 in the case of science superman K a British colony, and there is feet above sea level, and surrounded Professor Vishva Dixit he has strong cultural and societal demarcation by the lush green of tea plantations, one too. Beginning in Kenya and of ethnicities, with separate schools, this must have seemed a world away Vishva and his wife, Manjul, on a recent visit ending in California, this is the hospital and civic centres depending from the bleak and arid landscape of to the Laikipia anti-poaching unit in Kenya. story of a researcher who asked on race. Vishva Dixit was born into this the frontier. Perhaps aptly, one theory big questions of himself and the discordant atmosphere a decade after for the etymology of the name of the world, and went on to pioneer a his physician parents were sent to Kenya town ‘Kericho’ is that it derives from the lecturer, Professor Hettiaratchi, left a that a career in public health was not for his medical degree recognised in the field of research into cell death, from India on colonial service. Initially, Kipsigis word for hospital, ‘kerichek’; so particular impression; revealing to the him. He felt that as a physician, he could United States, and following a good word caspases and apoptosis. -
Developing Caspase-1 Biosensors to Monitor Inflammation in Vitro and in Vivo
Loyola University Chicago Loyola eCommons Dissertations Theses and Dissertations 2020 Developing Caspase-1 Biosensors to Monitor Inflammation in Vitro and in Vivo Sarah Talley Follow this and additional works at: https://ecommons.luc.edu/luc_diss Part of the Immunology and Infectious Disease Commons Recommended Citation Talley, Sarah, "Developing Caspase-1 Biosensors to Monitor Inflammation in Vitro and in Vivo" (2020). Dissertations. 3827. https://ecommons.luc.edu/luc_diss/3827 This Dissertation is brought to you for free and open access by the Theses and Dissertations at Loyola eCommons. It has been accepted for inclusion in Dissertations by an authorized administrator of Loyola eCommons. For more information, please contact [email protected]. This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. Copyright © 2020 Sarah Talley LOYOLA UNIVERSITY CHICAGO DEVELOPING CASPASE-1 BIOSENSORS TO MONITOR INFLAMMATION IN VITRO AND IN VIVO A DISSERTATION SUBMITTED TO THE FACULTY OF THE GRADUATE SCHOOL IN CANDIDACY FOR THE DEGREE OF DOCTOR OF PHILOSOPHY PROGRAM IN INTEGRATIVE CELL BIOLOGY BY SARAH TALLEY CHICAGO, IL AUGUST 2020 TABLE OF CONTENTS LIST OF FIGURES v CHAPTER ONE: INTRODUCTION 1 CHAPTER TWO: REVIEW OF THE LITERATURE 5 Overview 5 Structure of Inflammasomes 6 Function of Inflammasomes 8 NLRP1 8 NLRP3 14 NLRC4 21 AIM2 24 PYRIN 28 Noncanonical Inflammasome Activation and Pyroptosis 31 Inflammatory Caspases 36 Caspase-1 36 Other Inflammatory Caspases 40 Biosensors and Novel Tools to Monitor -
June 2007 ASCB Newsletter Member Profile
ASCB Profile Gerald Rubin You need to be careful about what you wish for Janelia is focused on basic neurobiology and Gerry Rubin has been careful indeed. In and cutting-edge imaging technology and 2002, the Howard Hughes Medical Institute computational analysis needed to understand (HHMI) gave Rubin the scientific equivalent of neuronal circuitry. Completely funded from a magic lantern full of wishes: anything Rubin HHMI’s private coffers, Janelia is divorced from needed to create a breakthrough research insti- the vagaries and prejudices of the public funding tute. Late last year, the world got its first tenta- system. tive look at what Rubin has been wishing for: In designing Janelia, Rubin explains that he Janelia Farm, the new HHMI interdisciplinary tried to draw on the best aspects of places he’s neurobiology and imaging research campus in worked such as the Medical Research Council suburban Northern Virginia. (MRC) Laboratory for Molecular Biology in Janelia represents an initial $500 million Cambridge, England (where Rubin did his investment by HHMI in land, buildings, and Ph.D. work with Sydney Brenner) and the Photo by Paul Fetters Photo by Paul people, and a subsequent, projected annual Cold Spring Harbor Laboratory (CSHL; where Gerald Rubin operating cost of $100 million. The site just Rubin studied and did summer lab internships south of the Potomac River in exploding while an MIT undergraduate). He also was suburban Northern Virginia covers 689 acres; inspired by places that he’d admired from afar, only 60 are being developed currently. The like the famed AT&T Bell Labs in Murray Hill, central Landscape Building, at 317,000 square NJ. -
Lecture Slides
(J. American Chemical Association, 78, 3458-3459) The Secondary Structure of Complementary RNA E. Peter Geiduschek, John W. Moohr, and Smauel B. Weiss, Proceedings of The National Academy of Sciences, 48, 1078-1086, 1962. R.H. DOI RH, and S. SPIEGELMAN Homology test between the nucleic acid of an RNA virus and the DNA in the host cell. Science 1962 Dec 14 1270-2. MONTAGNIER L, SANDERS FK. REPLICATIVE FORM OF ENCEPHALOMYOCARDITIS VIRUS RIBONUCLEIC ACID. Nature. 1963 Aug 17;199:664-7. (Science 143, 1034-1036, March 6, 1964) WARNER RC, SAMUELS HH, ABBOTT MT, KRAKOW JS. (1963) Ribonucleic acid polymerase of Azotobacter vinelandii, II. Formation of DNA- RNA hybrids with single-stranded DNA as primer. Proc Natl Acad Sci U S A. 49:533-8. Double Stranded RNA as a Specific Biological Effector December 8, 2006 Karolinska Institute, Stockholm, Sweden Viral interference (Interferon) effects in animals M. Hoskins (1935) A protective action of neurotropic against viscerotropic yellow fever virus in Macacus rhesus. American Journal of Tropical Medicine, 15, 675-680 G. Findlay and F. MacCallum (1937) An interference phenomenon in relation to yellow fever and other viruses. J. Path. Bact. 44, 405-424. A. Isaacs and J. Lindenmann (1957) Virus Interference. I. The Interferon Proc. Royal Soc. B 147, 268-273. Proceedings of the National Academy of Sciences, USA, Volume 58, Pages 782-789. 1967 Promoter Make transgenic worms geneX Antisense Transcripts Interference (Development 113:503 [1991]) geneX Promoter Make transgeneic worms geneX SENSE Transcripts Also Interference! (Development 113:503 [1991]) In Vitro Promoter Make RNA in vitro geneX Antisense RNA Inject worm gonad Interference! (Guo and Kemphues, 1995) In Vitro geneX Promoter Make RNA in vitro geneX SENSE RNA Inject worm gonad Also Interference! (Guo and Kemphues, 1995) Craig Mello's RNAi Workshop: 1997 C.