Dr. Gary Ruvkun

Massachusetts General Hospital

Gary Ruvkun is a professor of genetics at Harvard Medical School. Dr. Ruvkun is a graduate of UC Berkeley (AB, Biophysics,1973) and Harvard (PhD Biophysics, 1982). Dr. Ruvkun’s research has explored regulation by microRNA genes and other tiny RNAs, control of longevity by insulin and other endocrine pathways, surveillance of toxins and other bacterial attacks, and detection of DNA or RNA from life on other planets ancestrally related to life on Earth. Dr. Ruvkun’s research revealed that the first microRNA discovered by the Ambros lab, lin-4, regulates the translation of a target gene, lin-14, to which it base pairs. The Ruvkun lab identified a second microRNA, let-7, which also regulates translation of its target gene via imperfect base pairing to the 3’ untranslated region of that mRNA, and showed that the sequence and regulation of the let-7 microRNA is conserved across animal phylogeny including humans. Thousands of miRNAs have subsequently been discovered and are now implicated in control of gene expression of across eukaryotic phylogeny. Saturation genetic analysis of the miRNA and RNAi pathways by the Ruvkun lab has revealed many of the protein cofactors that may mediate other steps in how miRNAs and siRNAs engage their targets. Some of these components may be developed as drug targets to enhance RNAi in mammals, a technical improvement that may be necessary to elevate a laboratory tool to a therapeutic modality. Dr. Ruvkun's laboratory has also discovered that an insulin-like signaling pathway controls C. elegans longevity.  Recent insulin signaling mutant analyses in mouse and humans have validated the generality of these discoveries in other animals. Dr. Ruvkun’s lab has also used full genome RNAi libraries to explore the complete set of genes that regulate aging. Many of the gene inactivations that cause increased survival encode the core conserved elements of cells that are targeted by toxins and virulence factors of bacteria. These core genetic pathways may be surveilled for toxin and virulence factor inhibition so that a decrement in function is interpreted as a microbial attack. Some of these pathways detect disruptions in the assembly of protein complexes such as the ribosome and the proteasome. The immune surveillance endocrine states that are induced by genetic variation in these surveillance pathways have already intersected with human glycosylation diseases and more generally may underlie some autoimmune diseases.

Over the past decade, Dr. Ruvkun’s lab, in collaboration with Maria Zuber, Chris Carr, and Micheal Finney, has been developing a small nucleic acid sequencing instrument to send to Mars to detect and sequence DNA. This instrument will test the theory that nucleic-acid- based life exchanged between Earth and Mars early in solar system evolution, using the exquisitely sensitive tools developed during the recent genomics revolution. Beyond the excitement of discovering life on another planet, the DNA sequences could provide a lens to the past.

Dr. Ruvkun’s honors and awards include the Rosenstiel Award (with Victor Ambros, Andy Fire, and Craig Mello), the Warren Triennial Prize (with Victor Ambros), the Benjamin Franklin Medal (with Victor Ambros and David Baulcombe), the Gairdner International Award (with Victor Ambros), the Albert Lasker Award for Basic Medical Research (with Victor Ambros and David Baulcombe), the Louisa Horwitz Prize (with Victor Ambros), the Shaul and Meira Massry Prize (with Victor Ambros), the Dan David Prize for Aging research (with Cynthia Kenyon), the Ipsen Foundation Longevity Prize, the Paul Janssen Award (with Victor Ambros), the Wolf Prize (with Victor Ambros), the Breakthrough Prize in Life Sciences, and the Gruber Prize (with Victor Ambros), and the National Academy of Sciences.

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