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

To view a recording of the 2021 Warren Alpert Prize Symposium. click link below

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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Past Symposia

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I am truly honored to be a recipient of the Alpert Award. It is especially meaningful to be recognized by my colleagues for discoveries that helped define the biology of the CTLA-4 and PD-1 pathways. The clinical translation of our fundamental understanding of these pathways illustrates the value of basic science research, and I hope this inspires other scientists.
- Arlene Sharpe

Arlene Sharpe | 2017 Recipient

Dr. Sharpe received her A.B. from Harvard University, where she did undergraduate thesis research in the laboratory of Dr. Jack Strominger.  She received her M.D. and Ph.D. degrees from Harvard Medical School where she did PhD thesis research on reovirus pathogenesis in the laboratory of Dr. Bernard Fields. She completed residency training in Pathology at Brigham and Women’s Hospital and postdoctoral research in the laboratory of Dr. Rudolf Jaenisch at the Whitehead Institute.

She currently is the George Fabyan Professor of Comparative Pathology, Head of the Division of Immunology, and Interim Co-Chair of the Department of Microbiology and Immunobiology at Harvard Medical School. She is a member of the Department of Pathology at Brigham and Women’s Hospital, an Associate Member at the Broad Institute of MIT and Harvard, and Leader of the Cancer Immunology Program at the Dana-Farber/Harvard Cancer Center. Dr. Sharpe is the Co-Director of the Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women’s Hospital. She has served as a member and chair of the NIH Hypersensitivity, Autoimmunity and Immune-mediated diseases (HAI) study section and is currently a member of NIAID Council. She is also the President of the American Association of Immunologists.

Dr. Sharpe’s functional analysis of costimulatory pathways regulating T cell activation has led to understanding of (1) the roles of B7-1 and B7-2 as positive regulators through CD28 and (2) negative regulators through CTLA-4, and (3) the role of PD-L1 and PD-L2 as negative regulators through PD-1. This functional characterization has provided critical translational insights that underpinned development of immunotherapies for cancer, autoimmune diseases, and transplant rejection.

Dr. Sharpe’s laboratory currently investigates the roles of T cell costimulatory and coinhibitory pathways in regulating T cell tolerance and effective antimicrobial and antitumor immunity, and translating fundamental understanding of T cell costimulation into new therapies for autoimmune diseases and cancer. Dr. Sharpe has published over 300 papers and was listed by Thomas Reuters as one of the most Highly Cited Researchers (top 1%) in 2014 and 2015 and a 2016 Citation Laureate. She received the William B. Coley Award for Distinguished Research in Tumor immunology in 2014 for her contributions to the discovery of PD-1 pathway.

View Past Recipients