David R. Liu

Last updated
David R. Liu
DavidRLiu2012.jpg
Liu in 2012
Born (1973-06-12) June 12, 1973 (age 50)
NationalityAmerican
Alma mater Harvard University (BA)
University of California, Berkeley (PhD)
OrganizationThe Liu Group
Known for
Scientific career
Fields Organic chemistry
Institutions Harvard University
Doctoral advisor Peter G. Schultz
Other academic advisors E.J. Corey
Chinese name
Traditional Chinese 劉如謙

David Ruchien Liu (born 1973) is an American molecular biologist and chemist. 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]

Contents

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 the University of California, Riverside. [2]

While in high school, Liu finished second in the 1990 national Westinghouse Science Talent Search. [4] He received his Bachelor of Arts in chemistry from Harvard University 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] [5] Liu received his Ph.D. in organic chemistry from the University of California, Berkeley in 1999, [6] supervised by Peter G. Schultz.

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 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 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 225 papers and is the inventor of more than 90 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 Science (NAS), [11] the National Academy of Medicine (NAM) and was named as a Fellow of the American Association for the Advancement of Science (AAAS). In 2022, he was awarded the King Faisal Prize in Medicine. [12]

Research

Liu's research group pioneered base editing, [13] [14] 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. [15] DNA-Templated Synthesis (DTS) generated some of the first examples of DNA-encoded libraries (DELs), now commonly used in drug discovery efforts in academia and in pharmaceutical companies. [16]

His lab also developed phage-assisted continuous evolution (PACE), [17] 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. [18] He has published over 230 peer-reviewed publications and his H-index is ≥130 according to Google Scholar. [19]

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), Chroma Medicine (genomic medicines that harness epigenetics), Resonance Medicine (novel enzymatic solutions for unment challenges in medicine), and Nvelop Therapeutics (novel gene editing delivery technologies). 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. [20] 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. [21]

Personal life

He met his wife, Julie Liu, while attending U.C Berkeley. [22]

Selected papers

See also

Related Research Articles

<span class="mw-page-title-main">Genome</span> All genetic material of an organism

In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA. The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as regulatory sequences, and often a substantial fraction of junk DNA with no evident function. Almost all eukaryotes have mitochondria and a small mitochondrial genome. Algae and plants also contain chloroplasts with a chloroplast genome.

<span class="mw-page-title-main">RNA</span> Family of large biological molecules

Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself or by forming a template for the production of proteins. RNA and deoxyribonucleic acid (DNA) are nucleic acids. The nucleic acids constitute one of the four major macromolecules essential for all known forms of life. RNA is assembled as a chain of nucleotides. Cellular organisms use messenger RNA (mRNA) to convey genetic information that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome.

<span class="mw-page-title-main">Genomics</span> Discipline in genetics

Genomics is an interdisciplinary field of biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes as well as its hierarchical, three-dimensional structural configuration. In contrast to genetics, which refers to the study of individual genes and their roles in inheritance, genomics aims at the collective characterization and quantification of all of an organism's genes, their interrelations and influence on the organism. Genes may direct the production of proteins with the assistance of enzymes and messenger molecules. In turn, proteins make up body structures such as organs and tissues as well as control chemical reactions and carry signals between cells. Genomics also involves the sequencing and analysis of genomes through uses of high throughput DNA sequencing and bioinformatics to assemble and analyze the function and structure of entire genomes. Advances in genomics have triggered a revolution in discovery-based research and systems biology to facilitate understanding of even the most complex biological systems such as the brain.

<span class="mw-page-title-main">Aptamer</span> Oligonucleotide or peptide molecules that bind specific targets

Aptamers are short sequences of artificial DNA, RNA, XNA, or peptide that bind a specific target molecule, or family of target molecules. They exhibit a range of affinities, with variable levels of off-target binding and are sometimes classified as chemical antibodies. Aptamers and antibodies can be used in many of the same applications, but the nucleic acid-based structure of aptamers, which are mostly oligonucleotides, is very different from the amino acid-based structure of antibodies, which are proteins. This difference can make aptamers a better choice than antibodies for some purposes.

<span class="mw-page-title-main">CRISPR</span> Family of DNA sequence found in prokaryotic organisms

CRISPR is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. These sequences are derived from DNA fragments of bacteriophages that had previously infected the prokaryote. They are used to detect and destroy DNA from similar bacteriophages during subsequent infections. Hence these sequences play a key role in the antiviral defense system of prokaryotes and provide a form of acquired immunity. CRISPR is found in approximately 50% of sequenced bacterial genomes and nearly 90% of sequenced archaea.

Pamela Ann Silver is an American cell and systems biologist and a bioengineer. She holds the Elliot T. and Onie H. Adams Professorship of Biochemistry and Systems Biology at Harvard Medical School in the Department of Systems Biology. Silver is one of the founding Core Faculty Members of the Wyss Institute for Biologically Inspired Engineering at Harvard University.

<span class="mw-page-title-main">Gene</span> Sequence of DNA or RNA that codes for an RNA or protein product

In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA, that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and non-coding genes.

<span class="mw-page-title-main">Stuart Schreiber</span> American chemist

Stuart Schreiber, Ph.D. is the Morris Loeb Research Professor at Harvard University, a co-Founder of the Broad Institute, Howard Hughes Medical Institute Investigator, Emeritus, and a member of the National Academy of Sciences and National Academy of Medicine. He currently leads Arena BioWorks.

<span class="mw-page-title-main">Directed evolution</span> Protein engineering method

Directed evolution (DE) is a method used in protein engineering that mimics the process of natural selection to steer proteins or nucleic acids toward a user-defined goal. It consists of subjecting a gene to iterative rounds of mutagenesis, selection and amplification. It can be performed in vivo, or in vitro. Directed evolution is used both for protein engineering as an alternative to rationally designing modified proteins, as well as for experimental evolution studies of fundamental evolutionary principles in a controlled, laboratory environment.

Aled Morgan Edwards is the founder and Chief Executive of the Structural Genomics Consortium, a charitable public-private partnership. He is Professor of Medical Genetics and Medical Biophysics at the University of Toronto, Visiting Professor of Chemical Biology at the University of Oxford, and Adjunct Professor at McGill University.

<span class="mw-page-title-main">ACD (gene)</span> Protein-coding gene in the species Homo sapiens

Adrenocortical dysplasia protein homolog is a protein that in humans is encoded by the ACD gene.

<span class="mw-page-title-main">Transcription activator-like effector nuclease</span>

Transcription activator-like effector nucleases (TALEN) are restriction enzymes that can be engineered to cut specific sequences of DNA. They are made by fusing a TAL effector DNA-binding domain to a DNA cleavage domain. Transcription activator-like effectors (TALEs) can be engineered to bind to practically any desired DNA sequence, so when combined with a nuclease, DNA can be cut at specific locations. The restriction enzymes can be introduced into cells, for use in gene editing or for genome editing in situ, a technique known as genome editing with engineered nucleases. Alongside zinc finger nucleases and CRISPR/Cas9, TALEN is a prominent tool in the field of genome editing.

<span class="mw-page-title-main">PRDM9</span> Protein-coding gene in humans

PR domain zinc finger protein 9 is a protein that in humans is encoded by the PRDM9 gene. PRDM9 is responsible for positioning recombination hotspots during meiosis by binding a DNA sequence motif encoded in its zinc finger domain. PRDM9 is the only speciation gene found so far in mammals, and is one of the fastest evolving genes in the genome.

Richard High Ebright is an American molecular biologist. He is the Board of Governors Professor of Chemistry and Chemical Biology at Rutgers University and Laboratory Director at the Waksman Institute of Microbiology.

<span class="mw-page-title-main">Cas9</span> Microbial protein found in Streptococcus pyogenes M1 GAS

Cas9 is a 160 kilodalton protein which plays a vital role in the immunological defense of certain bacteria against DNA viruses and plasmids, and is heavily utilized in genetic engineering applications. Its main function is to cut DNA and thereby alter a cell's genome. The CRISPR-Cas9 genome editing technique was a significant contributor to the Nobel Prize in Chemistry in 2020 being awarded to Emmanuelle Charpentier and Jennifer Doudna.

<span class="mw-page-title-main">Feng Zhang</span> Chinese–American biochemist

Feng Zhang is a Chinese–American biochemist. Zhang currently holds the James and Patricia Poitras Professorship in Neuroscience at the McGovern Institute for Brain Research and in the departments of Brain and Cognitive Sciences and Biological Engineering at the Massachusetts Institute of Technology. He also has appointments with the Broad Institute of MIT and Harvard. He is most well known for his central role in the development of optogenetics and CRISPR technologies.

<span class="mw-page-title-main">Chuan He</span> Chinese-American chemical biologist

Chuan He is a Chinese-American chemical biologist. He currently serves as the John T. Wilson Distinguished Service Professor at the University of Chicago, and an Investigator of the Howard Hughes Medical Institute. He is best known for his work in discovering and deciphering reversible RNA methylation in post-transcriptional gene expression regulation. He was awarded the 2023 Wolf Prize in Chemistry for his work in discovering and deciphering reversible RNA methylation in post-transcriptional gene expression regulation in addition to his contributions to the invention of TAB-seq, a biochemical method that can map 5-hydroxymethylcytosine (5hmC) at base-resolution genome-wide, as well as hmC-Seal, a method that covalently labels 5hmC for its detection and profiling.

J. Keith Joung is an American pathologist and molecular biologist who holds the Robert B. Colvin Endowed Chair in Pathology at Massachusetts General Hospital and is Professor of Pathology at Harvard Medical School. He is a leading figure in the field of genome editing and has pioneered the development of designer nucleases and sensitive off-target detection methods.

<span class="mw-page-title-main">CRISPR gene editing</span> Gene editing method

CRISPR gene editing is a genetic engineering technique in molecular biology by which the genomes of living organisms may be modified. It is based on a simplified version of the bacterial CRISPR-Cas9 antiviral defense system. By delivering the Cas9 nuclease complexed with a synthetic guide RNA (gRNA) into a cell, the cell's genome can be cut at a desired location, allowing existing genes to be removed and/or new ones added in vivo.

Prime editing is a 'search-and-replace' genome editing technology in molecular biology by which the genome of living organisms may be modified. The technology directly writes new genetic information into a targeted DNA site. It uses a fusion protein, consisting of a catalytically impaired Cas9 endonuclease fused to an engineered reverse transcriptase enzyme, and a prime editing guide RNA (pegRNA), capable of identifying the target site and providing the new genetic information to replace the target DNA nucleotides. It mediates targeted insertions, deletions, and base-to-base conversions without the need for double strand breaks (DSBs) or donor DNA templates.

References

  1. 1 2 "David R. Liu". Liu Group. 2018-10-22. Retrieved 2019-04-02.
  2. 1 2 3 "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. "Science Talent Search 1990". Society for Science. Retrieved 2023-04-18.
  5. Bradt, Steve (2 June 2005). "Chemist, card shark Liu takes off". Harvard Gazette.
  6. "CV". Google Docs. Retrieved 8 June 2021.
  7. "David R. Liu". chemistry.harvard.edu. Retrieved 2019-04-02.
  8. "David R. Liu, PhD Bio". HHMI. Archived from the original on 18 February 2013. Retrieved 29 December 2017.[ verification needed ]
  9. Citation error. See inline comment how to fix. [ verification needed ]
  10. Liu, David R. (23 April 2019), Can we cure genetic diseases by rewriting DNA? , retrieved 2019-04-25
  11. "News from the National Academy of Sciences". April 26, 2021. Retrieved July 4, 2021. Newly elected members and their affiliations at the time of election are: … Liu, David R.; investigator, Howard Hughes Medical Institute; and Thomas Dudley Cabot Professor of the Natural Sciences, department of chemistry and chemical biology, Harvard University, Cambridge, Mass., entry in member directory: "Member Directory". National Academy of Sciences. Retrieved July 4, 2021.
  12. King Faisal Prize 2022
  13. Komor, Alexis C.; Kim, Yongjoo B.; Packer, Michael S.; Zuris, John A.; Liu, David R. (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.
  14. Gaudelli, Nicole M.; Komor, Alexis C.; Rees, Holly A.; Packer, Michael S.; Badran, Ahmed H.; Bryson, David I.; Liu, David R. (November 2017). "Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage". Nature. 551 (7681): 464–471. Bibcode:2017Natur.551..464G. doi:10.1038/nature24644. ISSN   1476-4687. PMC   5726555 . PMID   29160308.
  15. 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.
  16. Clark, Matthew A.; Liu, David R. (2009-02-08). "Design, synthesis and selection of DNA-encoded small-molecule libraries". Nature Chemical Biology. 5 (9): 657–654. doi: 10.5059/yukigoseikyokaishi.66.590 . PMID   19648931.
  17. Dickinson, Bryan C.; Leconte, Aaron M.; Allen, Benjamin; Esvelt, Kevin M.; Liu, David R. (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.
  18. Rees, Holly A.; Liu, David R. (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.
  19. "David R. Liu". Google Scholar . Retrieved 13 December 2022.
  20. Brian Gormley, "Flagship Ventures Hatches Two More Health-Care Companies", The Wall Street Journal (March 17, 2011)
  21. Keown, Alex (November 22, 2017). "Cambridge's Ensemble Therapeutics Quietly Shuts Down After 13 Years". BioSpace.
  22. https://news.harvard.edu/gazette/story/2005/06/chemist-card-shark-liu-takes-off/