David R. Liu

David Ruchien Liu
David R. Liu (taken in 2012)
Born (1973-06-12) June 12, 1973
Riverside, California
Residence Lexington, Massachusetts
Citizenship United States
Alma mater Riverside Poly High School, Harvard University, University of California, Berkeley
Known for Nucleic acid templated chemistry, Directed evolution, Base editing
Scientific career
Institutions Harvard University
Doctoral advisor Peter G. Schultz
Other academic advisors E.J. Corey

David Ruchien Liu (劉如謙)(born June 12, 1973) is an American chemist and biochemist, best known for his work on the directed evolution and engineering of biological and synthetic molecules, the development of life sciences technologies including base editing, phage-assisted continuous evolution (PACE), and DNA-templated synthesis (DTS), and as a founder of biotechnology companies. He is Richard Merkin Professor in the Merkin Institute for Transformative Technologies in Healthcare of the Broad Institute, a Professor of Chemistry and Chemical Biology at Harvard University, and a Howard Hughes Medical Institute Investigator.[1]

Early life and education

Liu was born in Riverside, California on June 12, 1973. Both his parents immigrated to the United States from Taiwan[2][3] and met in graduate school at UCLA. His father is an aerospace engineer; his mother is a retired physics professor at U. C. Riverside. While in high school, he finished second in the 1990 national Westinghouse Science Talent Search. 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.[4][5]

Liu received his Ph.D. from UC Berkeley in 1999, supervised by Peter G. Schultz.[6][7]

Academic career

In 1999 Liu became assistant professor of chemistry and chemical biology at Harvard. He was promoted to associate professor in 2003, and to full professor in 2005, at which time he also became a Howard Hughes Medical Investigator.[6] 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.[8]

Liu's additional honors and awards include the NSF CAREER award (2001), Alfred P. Sloan Foundation Research Fellow (2002), the American Chemical Society Pure Chemistry Award (2006), and the Beckman Young Investigators Award.[9]

Research

Liu's research group developed DNA-templated organic 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.[10][11][12][13] He also developed phage-assisted continuous evolution (PACE), a technique that uses the short 10-minute lifespan of the M13 bacteriophage to achieve the rapid evolution of useful proteins.[5] The group also developed methods for using DNA templates for the synthesis of new polymers with tailor-made properties,[4][14] as well as methods for using "supercharged" proteins of unusually high net charge to deliver macromolecules into mammalian cells in vitro and in vivo.[15] In 2016 and afterwards, the Liu lab developed "base editing", a method of genome editing in which a base pair can be converted to a different one, without first introducing double-stranded DNA breaks.[16][17][18]

Commercial activity

Liu founded or co-founded Beam Therapeutics, Pairwise Plants, and Editas Medicine (NASDAQ: EDIT), three genome editing companies. The company 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.[19]

In 2011 Permeon Biologics was founded 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.[20]

References

  1. ↑ David R. Liu, Broad Institute, retrieved 2017-12-27.
  2. ↑ 台裔科學家劉如謙 入選2017十大科學人物, 自由時報, 2017-12-19
  3. ↑ 《自然》2017十大科學人物　台裔科學家劉如謙入選, 蘋果日報, 2017-12-19
  4. 1 2 Bradt, Steve (2 June 2005). "Chemist, card shark Liu takes off". Harvard Gazette.
  5. 1 2 "Asian American: David Liu Speeds Up Evolution of Therapeutic Proteins". Goldsea Asian American Business: Asian Media Group. April 18, 2011.
  6. 1 2 "David R. Liu, PhD Bio". HHMI. Retrieved 29 December 2017.
  7. ↑ "Curriculum Vitae: David R. Liu" (PDF). Liu Lab, Harvard University. Retrieved 29 December 2017.
  8. ↑ Steve Bradt, "Five honored as Harvard College Professors", Harvard Gazette (May 10, 2007)
  9. ↑ "Broad names David Liu core institute member". Broad Communications. 2016. Retrieved 1 August 2018.
  10. ↑ Gartner, ZJ; Liu, DR (July 2001). "The generality of DNA-templated synthesis as a basis for evolving non-natural small molecules". J. Am. Chem. Soc. 123: 6961–3. doi:10.1021/ja015873n. PMC 2820563. PMID 11448217.
  11. ↑ Kanan, MW; Rozenman, MM; Sakurai, K; Snyder, TM; Liu, DR (2004). "Reaction discovery enabled by DNA-templated synthesis and in vitro selection". Nature. 431: 545–9. doi:10.1038/nature02920. PMC 2814052. PMID 15457254.
  12. ↑ Gartner, ZJ; Tse, BN; Grubina, R; Doyon, JB; Snyder, TM; Liu, DR (September 2004). "DNA-templated organic synthesis and selection of a library of macrocycles". Science. 305: 1601–5. doi:10.1126/science.1102629. PMC 2814051. PMID 15319493.
  13. ↑ Georghiou, G; Kleiner, RE; Pulkoski-Gross, M; Liu, DR; Seeliger, MA (2012). "Highly specific, bisubstrate-competitive Src inhibitors from DNA-templated macrocycles". Nat. Chem. Biol. 8: 366–74. doi:10.1038/nchembio.792. PMC 3307835. PMID 22344177.
  14. ↑ Peter Reuell, "Evolutionary oomph", Harvard Gazette (April 1, 2013)
  15. ↑ Cronican, JJ; Thompson, DB; Beier, KT; McNaughton, BR; Cepko, CL; Liu, DR (2010). "Potent delivery of functional proteins into Mammalian cells in vitro and in vivo using a supercharged protein". ACS Chem. Biol. 5: 747–52. doi:10.1021/cb1001153. PMC 2924640. PMID 20545362.
  16. ↑ Komor, AC; Kim, YB; Packer, MS; Zuris, JA; Liu, DR (19 May 2016). "Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage". Nature. 533 (7603): 420–4. doi:10.1038/nature17946. PMC 4873371. PMID 27096365.
  17. ↑ Kim, YB; Komor, AC; Levy, JM; Packer, MS; Zhao, KT; Liu, DR (April 2017). "Increasing the genome-targeting scope and precision of base editing with engineered Cas9-cytidine deaminase fusions". Nature Biotechnology. 35 (4): 371–376. doi:10.1038/nbt.3803. PMC 5388574. PMID 28191901.
  18. ↑ Gaudelli, NM; Komor, AC; Rees, HA; Packer, MS; Badran, AH; Bryson, DI; Liu, DR (23 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. PMC 5726555. PMID 29160308.
  19. ↑ Keown, Alex (November 22, 2017). "Cambridge's Ensemble Therapeutics Quietly Shuts Down After 13 Years". BioSpace.
  20. ↑ Brian Gormley, "Flagship Ventures Hatches Two More Health-Care Companies", The Wall Street Journal (March 17, 2011)
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