Gary Ruvkun, PhD
Professor of Genetics
Harvard Medical School
2024 Nobel Prize in Physiology or Medicine Awardee (with Victor Ambros, PhD)
Gary Ruvkun is a professor of genetics at Harvard Medical School. He is a graduate of UC Berkeley (AB, Biophysics,1973) and Harvard (PhD Biophysics, 1982). Dr. Ruvkun began to work on genetics in the nematode C. elegans in 1982 as a Harvard Junior Fellow working with Bob Horvitz at MIT and Walter Gilbert at Harvard.
Dr. Ruvkun’s research has explored two major themes: regulation of developmental control genes by microRNA genes and other small RNAs, and control of longevity and metabolism. In a series of collaborative papers between 1989 and 1993 with Dr. Victor Ambros of Harvard University, Dartmouth Medical School, and now University of Massachusetts at Worcester, Dr. Ambros and Dr. Ruvkun reported that graded levels of the developmental timing control gene lin-14 are generated by the production of a regulatory RNA, the 21 nucleotide lin-4 miRNA discovered by the Ambros lab, which basepairs to complementary regulatory elements in the lin-14 3’ untranslated region. Dr. Ruvkun’s research revealed that these lin-4/lin-14 RNA duplexes repress translation. In 2000, the Ruvkun lab identified the second microRNA, let-7, which also regulates translation of its target gene via imperfect base pairing to the 3’ untranslated region of that mRNA. Also in 2000, the Ruvkun lab discovered that the sequence and regulation of the let-7 microRNA and the 3’ UTR complementarity to target genes is conserved across animal phylogeny. This was the first indication that miRNA regulation via 3’ UTR complementarity was a general eukaryotic regulatory mechanism.
Dr. Ruvkun has also studied the genes that collaborate with miRNAs and siRNAs and other small RNAs. In 2005, the Ruvkun lab published a genome scale RNA interference screen to discover 90 protein-coding genes needed for RNAi and related small RNA pathways, including miRNAs. The Ruvkun lab recently published a similar genome-wide screen of miRNA pathway cofactors. The Ruvkun lab also discovered that there is complex negative regulation of RNAi and competing small RNA pathways. In addition to revealing fundamental regulatory axes in biology, 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. elegansmetabolism and longevity. Animals with deficits in insulin-like signaling live up to 3 times longer than wild type. The Ruvkun laboratory also identified the major transcriptional output of insulin-like signaling across the animal kingdom, the daf-16 Forkhead transcription factor and the signal transduction components from the DAF-2 insulin receptor. These findings are also important for diabetes, and related insulin-like signaling pathways. The Ruvkun lab has also used full genome RNAi libraries to reveal a comprehensive set of genes that regulate aging and metabolism. Many of these genes are broadly conserved in animal phylogeny and reveal a neuroendocrine system that assesses and regulates energy stores.
Dr. Ruvkun’s honors and awards include the Rosenstiel Award from Brandeis University (with Victor Ambros, Andy Fire, and Craig Mello), the Warren Triennial Prize from Massachusetts General Hospital (with Victor Ambros), the Gairdner International Award from the Gairdner Foundation of Canada (with Victor Ambros), the Albert Lasker award (with Victor Ambros and David Baulcombe), the National Academy of Sciences, and the 2024 Nobel Prize in Medicine or Physiology (with Victor Ambros).