Gary Ruvkun
Harvard University
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Primary Section: 26, Genetics Secondary Section: 22, Cellular and Developmental Biology Membership Type:
Member
(elected 2008)
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Biosketch
Professor of Genetics, Harvard Medical School Department of Molecular Biology, Massachusetts General Hospital 1985 – present Professor of Genetics, Harvard Medical School 1982 1985 Junior Fellow, Society of Fellows, Harvard University 1982 Ph.D. Harvard University (Biophysics) 1973 A.B. University of California at Berkeley (Biophysics) 2004 Rosenstiel Award, Brandeis University (with Victor Ambros, Andy Fire, Craig Mello) 2008 National Academy of Sciences 2008 Benjamin Franklin Medal, Franklin Institute (with Victor Ambros and David Baulcombe) 2008 Albert Lasker Award for Basic Medical Research (with Victor Ambros and David Baulcombe) 2008 Canada Gairdner International Award (with Victor Ambros) 2008 Warren Triennial Prize, Massachusetts General Hospital (with Victor Ambros) 2009 Louisa Gross Horwitz Prize, Columbia University (with Victor Ambros) 2009 American Academy of Arts and Sciences 2009 Shaul and Meira Massry Prize (with Victor Ambros) 2009 National Academy of Medicine 2011 Dan David Prize (with Cynthia Kenyon) 2012 Paul Janssen Award for Biomedical Research (with Victor Ambros) 2014 Wolf Prize in Medicine (with Victor Ambros) 2014 Gruber Genetics Prize (with Victor Ambros and David Baulcombe) 2015 Breakthrough Prize in Life Sciences 2016 March of Dimes Prize in Developmental Biology (with Victor Ambros) 2019 American Philosophical Society.
Research Interests
Research in the Ruvkun lab has explored three major themes: microRNA genes and other small RNAs, control of longevity and immune surveillance, and detection of life on other planets. We discovered in collaboration with Victor Ambros in 1992 that the first microRNA, lin-4, regulates the translation of a target gene, lin-14, to which it base pairs with the loops and bulges that are common in folded RNAs. The Ruvkun lab identified the second microRNA in 2000, let-7, which also regulates translation of its target gene via imperfect base pairing, and showed that the sequence and regulation of the let-7 microRNA is conserved across animal phylogeny including humans. Thousands of miRNAs across eukaryotic phylogeny were subsequently discovered by dozens of laboratories. The miRNA field has grown from the two back-to-back papers by Ambros and Ruvkun in 1993 to more than 100,000 references in 2021. The anatomy of the pairing of the lin-4 miRNA to the lin-14 mRNA and the let-7 miRNA pairing to the lin-41 target mRNA, with the bulges and loops in those duplexes are still the paradigm from which the thousands of newly discovered miRNAs and their targets are viewed. miRNAs are now used in the clinic to type tumors. miRNAs are now implicated in heart disease, in viral pathogenesis, in regulation of neural function and disease, in the transition from totipotent stem cells to differentiated cells. In plants, miRNAs mediate a variety of developmental and physiological transitions and turn out to have been key players in the domestication of corn. Human therapies based on microRNA regulation are already in clinical trials for heart disease. We also discovered many of the genes that collaborate with microRNAs and siRNAs and other small RNAs. In addition to revealing fundamental regulatory axes in biology, some of these components may be developed as drug targets to enhance RNAi in animals and plants. The Ruvkun lab discovered that an insulin-like signaling pathway controls C. elegans metabolism and longevity. Genetic analysis in mouse and humans have validated the generality of insulin-regulation of aging. We used full genome RNAi libraries to explore the complete set of genes that regulate aging. Many of the lifespan-increasing gene inactivations target conserved genes that are also targeted by microbial antibiotics. Translation of mRNA and the mitochondrial electron transport chain are key targets of microbial toxins, and we are intensively studying the defense responses to such perceived attacks. Surveillance for these microbial attacks is coupled to detoxification and immune responses as well as endocrine axes of fertility and aging. We discovered that a wide range of bacterial species have evolved pathways to disrupt the eukaryotic surveillance of bacteria. These bacterial pathways can be dissected using a combination of genetic analysis of the bacteria and the animal host.
