Getting the message: How elucidation of messenger RNA formation empowered RNA therapeutics

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2021 Warren Alpert Foundation Prize Virtual Symposium

In honor of Lynne Maquat and Joan Steitz for the discovery of fundamental pathways and mechanisms that ensure accurate RNA splicing and quality control of gene expression involving RNA.

Lynne Maquat

Lynne Maquat | 2021 Recipient

Dr. Lynne Maquat is the J. Lowell Orbison Endowed Chair, Professor of Biochemistry & Biophysics who holds concomitant appointments in Pediatrics and in Oncology, Founding Director of the Center for RNA Biology, and Founding Chair of Graduate Women in Science at the University of Rochester, Rochester, NY. After obtaining her PhD in Biochemistry from the University of Wisconsin-Madison and undertaking post-doctoral work at the McArdle Laboratory for Cancer Research, she joined Roswell Park Cancer Institute before moving to the University of Rochester. Dr. Maquat’s research focuses on the molecular basis of human diseases, with particular interest in mechanisms of mRNA decay. Dr. Maquat discovered nonsense-mediated mRNA decay (NMD) in human diseases in 1981 and, subsequently, the exon-junction complex (EJC) and how the EJC marks mRNAs for a quality-control “pioneer” round of protein synthesis. She also discovered Staufen-mediated mRNA decay, which mechanistically competes with NMD and, by so doing, new roles for short interspersed elements and long non-coding RNAs. Additionally, she has defined a new mechanism by which microRNAs are degraded, thereby regulating mRNAs so as to promote the cell cycle.

Maquat is an elected Fellow of the American Association for the Advancement of Science (2006); an elected Member of the American Academy of Arts & Sciences (2006), the National Academy of Sciences (2011), and the National Academy of Medicine (2017); and a Batsheva de Rothschild Fellow of the Israel Academy of Sciences & Humanities (2012-3). She received the William C. Rose Award from the American Society for Biochemistry & Molecular Biology (2014), a Canada Gairdner International Award (2015), the international RNA Society Lifetime Achievement Award in Service (2010) and in Science (2017), the FASEB Excellence in Science Award (2018), the Vanderbilt Prize in Biomedical Science (2017), the Wiley Prize in Biomedical Sciences (2018), the International Union of Biochemistry and Molecular Biology Medal (2019), and the Wolf Prize in Medicine (2021). Maquat is well-known for her efforts to promote women in science.

Joan Steitz

Joan Steitz | 2021 Recipient

Joan A. Steitz, Ph.D., is the Sterling Professor of Molecular Biophysics and Biochemistry at Yale University School of Medicine and a Howard Hughes Medical Institute Investigator.Steitz earned her BS in chemistry from Antioch College in 1963. Significant findings from her work emerged as early as 1967, when her Harvard PhD thesis with Jim Watson examined the test-tube assembly of a ribonucleic acid (RNA) bacteriophage (antibacterial virus) known as R17.

Steitz spent the next three years in postdoctoral studies at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England, where she used early methods for determining the biochemical sequence of RNA to study how ribosomes know where to initiate protein synthesis on bacterial mRNAs. In 1970, she was appointed assistant professor of Molecular Biophysics and Biochemistry at Yale, becoming full professor in 1978. At Yale, she established a laboratory dedicated to the study of RNA structure and function. In 1979, Steitz and her colleagues described a group of cellular particles called small nuclear ribonucleoproteins (snRNPs), a breakthrough in understanding how RNA is spliced. Subsequently, her laboratory has defined the structures and functions of other noncoding RNPs, such as those that guide the modification of ribosomal RNAs, microRNAs and several produced by transforming herpesviruses.

Steitz is an investigator of the Howard Hughes Medical Institute, a member of the American Academy of Arts and Sciences, American Philosophical Society, National Academy of Sciences, and Institute of Medicine. Her many honors include the U.S. Steel Foundation Award in Molecular Biology (1982); National Medal of Science (1986); FASEB Excellence in Science Award (2003); RNA Society Lifetime Achievement Award (2004); Gairdner Foundation International Award (2006); Albany Medical Center Prize in Medicine and Biomedical Research (2008) [shared with Elizabeth Blackburn]; Pearl Meister Greengard Prize (2012); La grande médaille 2013 de l'Académie des sciences, Insititut de France; Foreign Member of the Royal Society of London (2014); Herbert Tabor Award, American Society of Biochemistry and Molecular Biology (2015); Biopolymers Murray Goodman Memorial Prize, American Chemical Society (2015); William Clyde DeVane Award for Teaching Excellence, Yale University (2016); Jonathan Kraft Prize for Excellence in Cancer Research (2016); ASCB Inaugural Fellow (2016); Lasker~Koshland Special Achievement Award in Medical Science, the Albert and Mary Lasker Foundation  (2018); and the Wolf Prize in Medicine (shared with Lynne Maquat and Adrian Krainer). Dr. Steitz has been awarded 19 honorary degrees.

Symposium Program

Each year the recipient(s) of the Warren Alpert Foundation Prize are recognized at a scientific symposium hosted by Harvard Medical School.

Opening Remarks

George Q. Daley, MD, PhD

Dean of Harvard Medical School; Caroline Shields Walker Professor of Medicine

Moderator

Karen Adelman, PhD

Professor of Biological Chemistry and Molecular Pharmacology; Harvard Medical School

Presentations

Phillip Sharp, PhD

Institute Professor, Koch Institute and Department of Biology Massachusetts Institute of Technology

RNA Condensates in Transcription and RNA Splicing

Joan Steitz, PhD

Sterling Professor of Molecular Biophysics and Biochemistry; Investigator, Howard Hughes Medical Institute Yale University School of Medicine

Viral Noncoding RNAs: New Functions, New Structures

Lynne E. Maquat, PhD

J. Lowell Orbison Endowed Chair, Professor of Biochemistry & Biophysics University of Rochester Medical Center

Nonsense-mediated mRNA Decay and Human Disease: Guardian and Executor of Gene Expression

Eugene Yeo, PhD

Professor of Cellular & Molecular Medicine University of California San Diego

RNA binding proteins as regulators, drugs and drug targets

Melissa J. Moore, PhD

Chief Scientific Officer, Platform Research Moderna Therapeutics

RNA as Medicine

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I would like to express my sincere appreciation to the Warren Alpert Foundation and Harvard Medical School for awarding me such a great honor. For me, this award is not only an honor but a responsibility.
- Tu Youyou

Tu Youyou | 2015 Recipient

For their pioneering discoveries in chemistry and parasitology, and personal commitments to translate these into effective chemotherapeutic and vaccine-based approaches to control malaria - their collective work will impact millions of lives globally particularly in the developing countries.

Tu Youyou is currently a Professor and Director of Qinghaosu Research Center at Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences.

Tu joined the Institute of Chinese Materia Medica (ICMM), China Academy of Traditional Chinese Medicine (CATCM) (renamed China Academy of Chinese Medical Sciences, CACMS in 2005) in 1955 after graduation from School of Pharmacy, Beijing Medical College (1951 – 1955).  She late attended a two and half year course on the traditional Chinese medicine (TCM) (1959-1962) - an in depth training specifically designed and offered to the graduates with Western medical background.  Over more than forty years, Tu has been working in the institute as a research assistant, assistant professor, associate professor, professor and director of the Chemistry Department.  She also holds a chief professor position of CACMS as well as members of Phytochemistry Society of China Pharmaceutical Association; Chinese Society of Traditional and Natural Drugs; Council member and Founding Member of Chinese Association of Invention; Executive Committee of All-China Women's Federation (1988-93) and a committee member of Beijing Committee of Natural Science Foundation (1995-97).

Tu’s research on anti-malaria drugs started in 1969 when she was appointed to head the Project 523 research group at the institute.  Project 523 was a secret military program initiated by the Chinese leadership in 1967 in supporting Vietnam government for searching medicines to treat anti chloroquine-resistant malaria.  Tremendous efforts had been made both in US and China but no effective drugs were found by the time Tu accepted the task.

Tu started with collection of over 2000 candidate recipes from which she and her team later screened over hundreds of herbal extracts.  Only one of the extracts from Qinghao (Artemisia annua L.) showed some promising effect, which however was not consistent and reproducible.  Tu further reviewed all available tradition Chinese medicine literatures and noticed a paragraph “Take a handful of Qinghao, soak in two liters of water, strain the liquid, and drink” in the Handbook of Prescriptions for Emergencies (340 CE) authored by Ge Hong.  She realized that the heating applied during extraction might have damaged the active components in the herb.  With this in mind, Tu re-designed low temperature extraction approaches using the solvents with low boiling points.  On the 4th October 1971, a neutral ether extract numbered 191 was found 100% effective in clearing Plasmodia in the mice and monkey test models.  To prove safety of the Qinghao extract and expedite the project, Tu and other two colleagues volunteered in the toxicity study on themselves in July 1972.  Between August and October 1972, Tu and her team carried out the first clinical trial in southern China in which all thirty-one patients treated with the Qinghao extract recovered from the disease.  Subsequent to the first clinical trial, Tu and her colleagues further purified the extract and obtained a pure active crystalline in November 1972.  The compound was late named Qinghaosu (Artemisinin).

Over last several decades, Tu has continued her effort in fighting against malaria.  She and her colleagues developed artemisinin into a medicine and late the team further developed dihydro-artemisinin, another anti-malaria drug, which is ten fold more effective than artemisinin itself.

Tu’s achievement in the discovery of artemisinin and its application in the malaria treatment as well as her unanimous contribution to the healthcare of human being have been well recognized nationally and internationally.  She was honored the Lasker ~ Debakey Clinical Medical Research Award in 2011.  Tu also received numerous awards nationally which include “Award for Progress in Anti-malarial Research Achieved by Project 523 Scientific Team” honored by China National Congress of Science and Technology (1978); “National Scientific Discovery Award” for Anti-malaria Drug-Qinghaosu by the China Ministry of Science and Technology (1979); “Invention Award” (as the first inventor) by China National Congress for Awards in Science and Technology (1982); “Award of Young and Middle-aged Experts with Outstanding Contribution” by the Chinese Government (1984); “The Top Honorary Award” by China Academy of Traditional Chinese Medicine (1992); “The Top Ten National Achievements for Progress in Science and Technology” by China National Committee of Science and Technology (1992); “First-Class Award of National Achievements in Science and Technology” by China National Award Committee for Advances in Science and Technology (1992); “National Model” by China State Council (1995); “Award for Outstanding Achievement in Traditional Chinese Medicine” by Guangzhou Zhongjing Award Foundation for Traditional Chinese Medicine (1995); “Outstanding Scientific Achievement Award” by Qiu Shi Science and Technologies Foundation of Hong Kong (1996); “Top Ten Health Achievements in New China” by China Ministry of Health (1997); “Female Inventor of the New Century” by China National Bureau of Intellectual Property (2002); “Golden Medal of the 14th National Invention Exhibition” by China National Bureau of Intellectual Property (2003); “Award for Development of Chinese Materia Medica” by Cyrus Chung Ying Tang Foundation, (2009).  She also received “Prince Mahidol Award” by Thailand Prince Mahidol Award Foundation (2003),  “GlaxoSmithKline Award for Outstanding Achievements in Life Science” (2011), Lasker~DeBakey Clinical Medical Research Award(2011), and the Nobel Prize in Physiology or Medicine(2015).

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