David R. Liu

David Ruchien Liu (born 1973) is an American chemist and biologist. He is the Richard Merkin Professor, Director of the Merkin Institute of Transformative Technologies in Healthcare, and Vice-Chair of the Faculty at the Broad Institute of Harvard and MIT; Thomas Dudley Cabot Professor of the Natural Sciences and Professor of Chemistry and Chemical Biology at Harvard University; and Howard Hughes Medical Institute Investigator.[1]

David R. Liu
Liu in 2012
Born (1973-06-12) June 12, 1973
Riverside, California
NationalityAmerican
Alma materRiverside Poly High School, Harvard University, University of California, Berkeley
Known forNucleic acid templated chemistry, Directed evolution, Base editing, Prime editing
Scientific career
InstitutionsHarvard University
Doctoral advisorPeter G. Schultz
Other academic advisorsE.J. Corey
Chinese name
Traditional Chinese劉如謙

Early life and education

Liu was born in Riverside, California on June 12, 1973.[2] Both his parents immigrated to the United States from Taiwan.[3] His father is an aerospace engineer; his mother is a retired physics professor at U. C. Riverside.[2] While in high school, he finished second in the 1990 national Westinghouse Science Talent Search.[2] He received a B.A. in chemistry from Harvard in 1994, graduating summa cum laude and first in his class. While an undergraduate, he worked in the synthetic chemistry laboratory of Nobel Laureate E.J. Corey.[2][4] Liu received his Ph.D. from UC Berkeley in 1999, supervised by Peter G. Schultz.[5][6]

Academic career

Liu graduated first in his class at Harvard in 1994.[7] He performed organic and bioorganic chemistry research on sterol biosynthesis under Professor E. J. Corey's guidance as an undergraduate. During his Ph.D. research with Professor Peter Schultz at U. C. Berkeley, Liu initiated the first general effort to expand the genetic code in living cells. He earned his Ph.D. in 1999 and became assistant professor of chemistry and chemical biology at Harvard University in the same year. He was promoted to associate professor in 2003 and to full professor in 2005. Liu became a Howard Hughes Medical Investigator[8] in 2005 and joined the JASONs, academic science advisors to the U.S. government, in 2009. He was honored as a Harvard College Professor in 2007, in part for his undergraduate teaching. His introductory life sciences course, beginning in 2005, became Harvard's largest natural sciences course.[9]

Liu has earned several university-wide distinctions for teaching at Harvard, including the Joseph R. Levenson Memorial Teaching Prize, the Roslyn Abramson Award, and a Harvard College Professorship. Liu has published more than 165 papers and is the inventor of more than 60 issued U.S. patents. His research accomplishments have earned distinctions including the Ronald Breslow Award for Biomimetic Chemistry, the American Chemical Society Pure Chemistry Award, the Arthur C. Cope Young Scholar Award, and awards from the Sloan Foundation, Beckman Foundation, NSF CAREER Program, and Searle Scholars Program. In 2016 he was named one of the Top 20 Translational Researchers in the world by Nature Biotechnology, and in 2017 and 2019 was named to the Nature’s 10 researchers in world and to the Foreign Policy Leading Global Thinkers.[1] In April, 2019, Liu delivered a TED talk on base editing in Vancouver at TED2019, resulting in a standing ovation from the live audience. [10] In 2019, prime editing was named as one of Nature's 10 remarkable papers from 2019 and one of The Scientist's top technical advances. In 2020, Liu earned the American Chemical Society David Perlman Award and the American Chemical Society ACS Chemical Biology Lectureship Award, was elected to the National Academy of Medicine (NAM) and was named as a Fellow of the American Association for the Advancement of Science (AAAS).

Research

Liu's research group pioneered base editing,[11][12] a new method of genome editing that enables the direct and precise conversion of a single base to another base in the genome of living cells, without making DNA double-stranded breaks (DSBs) that lead to complex mixtures of insertions, deletions, and DNA rearrangements. Liu's research group also pioneered prime editing, a versatile genome editing method that can install all possible base-to-base conversions, insertions, deletions, and combinations in mammalian cells without requiring double-strand DNA breaks or donor DNA templates. [13] Additionally, Liu's group developed DNA-templated synthesis (DTS), a technique to translate DNA sequences into synthetic small molecules, rather than proteins, and applied DTS to the discovery of bioactive small molecules and new chemical reactions.[14] His lab also developed phage-assisted continuous evolution (PACE),[15] a technique that uses the short 10-minute lifespan of M13 bacteriophage to achieve the rapid evolution of useful proteins. The lab has used PACE and its directed evolution efforts to generate new genome editing tools that allow for expanded DNA accessibility and DNA base conversions.[16]

Commercial activity

Liu co-founded Editas Medicine (genome editing with CRISPR nucleases for human therapeutics), Pairwise Plants (genome editing for agriculture), Beam Therapeutics (base editing for human therapeutics), Exo Therapeutics (novel small-molecule drug discovery). He is the scientific founder of Prime Medicine (prime editing for human therapeutics).

Liu also founded Permeon Biologics and Ensemble Therapeutics. Permeon Biologics was founded in 2011 by Liu and Flagship Ventures to develop a class of proteins to enable the transport of large molecules such as antibodies into cells to facilitate development of "intrabody" therapeutics and ceased its operations in 2015.[17] Ensemble Therapeutics was founded in 2004 with funding from Flagship Ventures to develop Liu's work on macrocycles; the company raised about $40M and struck several pharmaceutical partnerships, but was shut down in 2017 before any of its lead compounds had reached the market.[18]

Selected papers

See also

References
  1. "David R. Liu". Liu Group. 2018-10-22. Retrieved 2019-04-02.
  2. "Asian American: David Liu Speeds Up Evolution of Therapeutic Proteins". Goldsea Asian American Business: Asian Media Group. April 18, 2011.
  3. Yang, Sophia (December 19, 2017). "Taiwanese-American named scientist of the yea... | Taiwan News". Taiwan News.
  4. Bradt, Steve (2 June 2005). "Chemist, card shark Liu takes off". Harvard Gazette.
  5. "David R. Liu, PhD Bio". HHMI. Retrieved 29 December 2017.
  6. "Curriculum Vitae: David R. Liu" (PDF). Liu Lab, Harvard University. Retrieved 29 December 2017.
  7. "David R. Liu". chemistry.harvard.edu. Retrieved 2019-04-02.
  8. "David R. Liu, PhD Bio". HHMI. Retrieved 29 December 2017.
  9. Citation error. See inline comment how to fix.
  10. Liu, David R., Can we cure genetic diseases by rewriting DNA?, retrieved 2019-04-25
  11. Liu, David R.; Zuris, John A.; Packer, Michael S.; Kim, Yongjoo B.; Komor, Alexis C. (May 2016). "Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage". Nature. 533 (7603): 420–424. Bibcode:2016Natur.533..420K. doi:10.1038/nature17946. ISSN 1476-4687. PMC 4873371. PMID 27096365.
  12. Liu, David R.; Bryson, David I.; Badran, Ahmed H.; Packer, Michael S.; Rees, Holly A.; Komor, Alexis C.; Gaudelli, Nicole M. (November 2017). "Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage". Nature. 551 (7681): 464–471. doi:10.1038/nature24644. ISSN 1476-4687. PMC 5726555. PMID 29160308.
  13. Anzalone, Andrew V.; Randolph, Peyton B.; Davis, Jessie R.; Sousa, Alexander A.; Koblan, Luke W.; Levy, Jonathan M.; Chen, Peter J.; Wilson, Christopher; Newby, Gregory A.; Raguram, Aditya; Liu, David R. (2019-10-21). "Search-and-replace genome editing without double-strand breaks or donor DNA". Nature. 576 (7785): 149–157. Bibcode:2019Natur.576..149A. doi:10.1038/s41586-019-1711-4. ISSN 1476-4687. PMC 6907074. PMID 31634902.
  14. Liu, David R.; Sakurai, Kaori (2008-06-01). "DNA-Templated Organic Synthesis (DTS): A Novel Approach to the Discovery of Functional Small Molecules Based on Nature's Evolutionary Principles". Journal of Synthetic Organic Chemistry, Japan. 66 (6): 590–604. doi:10.5059/yukigoseikyokaishi.66.590. ISSN 0037-9980.
  15. Liu, David R.; Esvelt, Kevin M.; Allen, Benjamin; Leconte, Aaron M.; Dickinson, Bryan C. (2013-05-28). "Experimental interrogation of the path dependence and stochasticity of protein evolution using phage-assisted continuous evolution". Proceedings of the National Academy of Sciences. 110 (22): 9007–9012. Bibcode:2013PNAS..110.9007D. doi:10.1073/pnas.1220670110. ISSN 0027-8424. PMC 3670371. PMID 23674678.
  16. David R. Liu; Rees, Holly A. (December 2018). "Base editing: precision chemistry on the genome and transcriptome of living cells". Nature Reviews Genetics. 19 (12): 770–788. doi:10.1038/s41576-018-0059-1. ISSN 1471-0064. PMC 6535181. PMID 30323312.
  17. Brian Gormley, "Flagship Ventures Hatches Two More Health-Care Companies", The Wall Street Journal (March 17, 2011)
  18. Keown, Alex (November 22, 2017). "Cambridge's Ensemble Therapeutics Quietly Shuts Down After 13 Years". BioSpace.
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