Research

The CRISPR/Cas9 system is a robust genome editing tool that has revolutionized genetic studies in human cells, animals and plants. The core of technology is the enzyme Cas9, an RNA-guided DNA endonuclease that induces a double-strand break at the guide RNA-specified chromosomal locus of interest. My research focuses on developing methods to enable robust, precise and safe genome manipulations in human genome. Current projects include:

  1. Understanding DNA repair mechanism to enable efficient Cas9-mediated homologous recombination.
  2. Discovering and characterizing orthogonal CRISPR/Cas systems.
  3. Expanding Cas9 ribonucleoprotein nucleofection for transcription and epigenetic regulations.
Degrees and Positions Held
Positions Held
  • 2016 – present   Assistant Research Fellow, Institute of Biological Chemistry, Academia Sinica, Taiwan
  • 2012 – 2015   Postdoctoral fellow, Department of Molecular and Cell Biology, University of California, Berkeley, USA
  • 2004 – 2004   Research assistant, Department of Biochemistry, The Ohio State University, USA
  • 2001 – 2003   Research assistant, Institute of Chemistry, Academia Sinica, Taiwan
Degrees
  • 2006 – 2012   Ph.D., Microbiology, University of Illinois at Urbana-Champaign, USA
  • 2004 – 2006   M.S., Biochemistry, The Ohio State University, USA
  • 1996 – 2001   B.S., Biology, University of British Columbia, Canada
Selected Publications
TIM-mediated inhibition of HIV-1 release is antagonized by Nef but potentiated by SERINC proteins.
Li MH, Waheed AA, Yu JY, Zeng C, Chen HY, Zheng YM, Feizpour A, Reinhard BM, Gummuluru S, Lin S, Freed EO & Liu SL
Proc. Natl. Acad. Sci. USA (2019)
Biosynthesis of Complex Indole Alkaloids: Elucidation of the Concise Pathway of Okaramines.
Lai CY, Lo IW, Hewage RT, Chen YC, Chen CT, Lee CF, Lin S, Tang MC & Lin HC
Angew. Chem. Int. Ed. Engl. (2017)
Generation of knock-in primary human T cells using Cas9 ribonucleoproteins.
Schumann K, Lin S, Boyer E, Simeonov DR, Subramaniam M, Gate RE, Haliburton GE, Ye CJ, Bluestone JA, Doudna JA & Marson A
Proc. Natl. Acad. Sci. USA (2015)
Enhanced homology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery.
Lin S, Staahl B & Doudna JA
eLIFE (2014)
Structures of Cas9 endonucleases reveal RNA-mediated conformational activation.
Jinek M, Jiang F, Taylor DW, Sternberg SH, Kaya E, Ma E, Anders C, Hauer M, Zhou K, Lin S, Kaplan M, Iavarone AT, Charpentier E, Nogales E & Doudna JA
Science (2014)
High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity.
Pattanayak V, Lin S, Guilinger JP, Ma E, Doudna JA & Liu DR
Nat. Biotechnol. (2013)
Precise and Heritable Genome Editing in Evolutionarily Diverse Nematodes Using TALENs and CRISPR/Cas9 to Engineer Insertions and Deletions.
Lo TW, Pickle CS, Lin S, Ralston EJ, Gurling M, Schartner CM, Bian Q, Doudna JA & Meyer BJ
Genetics (2013)
Structure of the enzyme-ACP substrate gatekeeper complex required for biotin synthesis.
Agarwal V, Lin S, Nair S & Cronan JE
Proc. Natl. Acad. Sci. USA (2012)
The BioC O-methyltransferase catalyzes methyl esterification of malonyl-acyl carrier protein, an essential step in biotin synthesis.
Lin S & Cronan JE
J. Biol. Chem. (2012)
Biotin synthesis begins by hijacking the fatty acid synthetic pathway.
Lin S, Hanson RE & Cronan JE
Nat. Chem. Biol. (2010)
Publications List
  1. Li M, Waheed AA, Yu J, Zeng C, Chen HY, Zheng YM, Feizpour A, Reinhard BM, Gummuluru S, (Lin S), Freed EO, Liu SL  (2019-03)  Proceedings of the National Academy of Sciences of the United States of America  116(12), 5705-5714  "TIM-mediated inhibition of HIV-1 release is antagonized by Nef but potentiated by SERINC proteins."
  2. Huang MC, Chu IT, Wang ZF, (Lin S), Chang TC, Chen CT  (2018-09)  International journal of molecular sciences  19(9), 2678  "A G-Quadruplex Structure in the Promoter Region of CLIC4 Functions as a Regulatory Element for Gene Expression."
  3. Lai CY, Lo IW, Hewage RT, Chen YC, Chen CT, Lee CF, (Lin S), Tang MC, Lin HC  (2017-08)  Angewandte Chemie-International Edition  56(32), 9478-9482  "Biosynthesis of Complex Indole Alkaloids: Elucidation of the Concise Pathway of Okaramines."
  4. Schumann K, (Lin S), Boyer E, Simeonov DR, Subramaniam M, Gate RE, Haliburton GE, Ye CJ, Bluestone JA, Doudna JA, Marson A  (2015-08)  Proceedings of the National Academy of Sciences of the United States of America  112(33), 10437-10442  "Generation of knock-in primary human T cells using Cas9 ribonucleoproteins."
  5. (Lin S), Staahl BT, Alla RK, Doudna JA  (2014-12)  eLife  3, e04766  "Enhanced homology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery."
  6. Jinek M, Jiang F, Taylor DW, Sternberg SH, Kaya E, Ma E, Anders C, Hauer M, Zhou K, (Lin S), Kaplan M, Iavarone AT, Charpentier E, Nogales E, Doudna JA  (2014-03)  Science  343(6176), 1247997  "Structures of Cas9 endonucleases reveal RNA-mediated conformational activation."
  7. Lo TW, Pickle CS, (Lin S), Ralston EJ, Gurling M, Schartner CM, Bian Q, Doudna JA, Meyer BJ  (2013-10)  Genetics  195(2), 331-348  "Precise and heritable genome editing in evolutionarily diverse nematodes using TALENs and CRISPR/Cas9 to engineer insertions and deletions."
  8. Pattanayak V, (Lin S), Guilinger JP, Ma E, Doudna JA, Liu DR  (2013-09)  Nature biotechnology  31(9), 839-843  "High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity."
  9. Jinek M, East A, Cheng A, (Lin S), Ma E, Doudna J  (2013-01)  eLife  2, e00471  "RNA-programmed genome editing in human cells."
  10. Agarwal V, (Lin S), Lukk T, Nair SK, Cronan JE  (2012-10)  Proceedings of the National Academy of Sciences of the United States of America  109(43), 17406-17411  "Structure of the enzyme-acyl carrier protein (ACP) substrate gatekeeper complex required for biotin synthesis."
  11. (Lin S), Cronan JE  (2012-10)  The Journal of biological chemistry  287(44), 37010-37020  "The BioC O-methyltransferase catalyzes methyl esterification of malonyl-acyl carrier protein, an essential step in biotin synthesis."
  12. Cronan JE, (Lin S)  (2011-06)  Current opinion in chemical biology  15(3), 407-413  "Synthesis of the alpha,omega-dicarboxylic acid precursor of biotin by the canonical fatty acid biosynthetic pathway."
  13. (Lin S), Hanson RE, Cronan JE  (2010-09)  Nature chemical biology  6(9), 682-688  "Biotin synthesis begins by hijacking the fatty acid synthetic pathway."

The CRISPR/Cas9 system is a robust genome editing tool that has revolutionized genetic studies in human cells, animals and plants. The core of technology is the enzyme Cas9, an RNA-guided DNA endonuclease that induces a double-strand break at the guide RNA-specified chromosomal locus of interest. My research focuses on developing methods to enable robust, precise and safe genome manipulations in human genome. Current projects include:

  1. Understanding DNA repair mechanism to enable efficient Cas9-mediated homologous recombination.
  2. Discovering and characterizing orthogonal CRISPR/Cas systems.
  3. Expanding Cas9 ribonucleoprotein nucleofection for transcription and epigenetic regulations.
Positions Held
  • 2016 – present   Assistant Research Fellow, Institute of Biological Chemistry, Academia Sinica, Taiwan
  • 2012 – 2015   Postdoctoral fellow, Department of Molecular and Cell Biology, University of California, Berkeley, USA
  • 2004 – 2004   Research assistant, Department of Biochemistry, The Ohio State University, USA
  • 2001 – 2003   Research assistant, Institute of Chemistry, Academia Sinica, Taiwan
Degrees
  • 2006 – 2012   Ph.D., Microbiology, University of Illinois at Urbana-Champaign, USA
  • 2004 – 2006   M.S., Biochemistry, The Ohio State University, USA
  • 1996 – 2001   B.S., Biology, University of British Columbia, Canada
TIM-mediated inhibition of HIV-1 release is antagonized by Nef but potentiated by SERINC proteins.
Li MH, Waheed AA, Yu JY, Zeng C, Chen HY, Zheng YM, Feizpour A, Reinhard BM, Gummuluru S, Lin S, Freed EO & Liu SL
Proc. Natl. Acad. Sci. USA (2019)
Biosynthesis of Complex Indole Alkaloids: Elucidation of the Concise Pathway of Okaramines.
Lai CY, Lo IW, Hewage RT, Chen YC, Chen CT, Lee CF, Lin S, Tang MC & Lin HC
Angew. Chem. Int. Ed. Engl. (2017)
Generation of knock-in primary human T cells using Cas9 ribonucleoproteins.
Schumann K, Lin S, Boyer E, Simeonov DR, Subramaniam M, Gate RE, Haliburton GE, Ye CJ, Bluestone JA, Doudna JA & Marson A
Proc. Natl. Acad. Sci. USA (2015)
Enhanced homology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery.
Lin S, Staahl B & Doudna JA
eLIFE (2014)
Structures of Cas9 endonucleases reveal RNA-mediated conformational activation.
Jinek M, Jiang F, Taylor DW, Sternberg SH, Kaya E, Ma E, Anders C, Hauer M, Zhou K, Lin S, Kaplan M, Iavarone AT, Charpentier E, Nogales E & Doudna JA
Science (2014)
High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity.
Pattanayak V, Lin S, Guilinger JP, Ma E, Doudna JA & Liu DR
Nat. Biotechnol. (2013)
Precise and Heritable Genome Editing in Evolutionarily Diverse Nematodes Using TALENs and CRISPR/Cas9 to Engineer Insertions and Deletions.
Lo TW, Pickle CS, Lin S, Ralston EJ, Gurling M, Schartner CM, Bian Q, Doudna JA & Meyer BJ
Genetics (2013)
Structure of the enzyme-ACP substrate gatekeeper complex required for biotin synthesis.
Agarwal V, Lin S, Nair S & Cronan JE
Proc. Natl. Acad. Sci. USA (2012)
The BioC O-methyltransferase catalyzes methyl esterification of malonyl-acyl carrier protein, an essential step in biotin synthesis.
Lin S & Cronan JE
J. Biol. Chem. (2012)
Biotin synthesis begins by hijacking the fatty acid synthetic pathway.
Lin S, Hanson RE & Cronan JE
Nat. Chem. Biol. (2010)
  1. Li M, Waheed AA, Yu J, Zeng C, Chen HY, Zheng YM, Feizpour A, Reinhard BM, Gummuluru S, (Lin S), Freed EO, Liu SL  (2019-03)  Proceedings of the National Academy of Sciences of the United States of America  116(12), 5705-5714  "TIM-mediated inhibition of HIV-1 release is antagonized by Nef but potentiated by SERINC proteins."
  2. Huang MC, Chu IT, Wang ZF, (Lin S), Chang TC, Chen CT  (2018-09)  International journal of molecular sciences  19(9), 2678  "A G-Quadruplex Structure in the Promoter Region of CLIC4 Functions as a Regulatory Element for Gene Expression."
  3. Lai CY, Lo IW, Hewage RT, Chen YC, Chen CT, Lee CF, (Lin S), Tang MC, Lin HC  (2017-08)  Angewandte Chemie-International Edition  56(32), 9478-9482  "Biosynthesis of Complex Indole Alkaloids: Elucidation of the Concise Pathway of Okaramines."
  4. Schumann K, (Lin S), Boyer E, Simeonov DR, Subramaniam M, Gate RE, Haliburton GE, Ye CJ, Bluestone JA, Doudna JA, Marson A  (2015-08)  Proceedings of the National Academy of Sciences of the United States of America  112(33), 10437-10442  "Generation of knock-in primary human T cells using Cas9 ribonucleoproteins."
  5. (Lin S), Staahl BT, Alla RK, Doudna JA  (2014-12)  eLife  3, e04766  "Enhanced homology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery."
  6. Jinek M, Jiang F, Taylor DW, Sternberg SH, Kaya E, Ma E, Anders C, Hauer M, Zhou K, (Lin S), Kaplan M, Iavarone AT, Charpentier E, Nogales E, Doudna JA  (2014-03)  Science  343(6176), 1247997  "Structures of Cas9 endonucleases reveal RNA-mediated conformational activation."
  7. Lo TW, Pickle CS, (Lin S), Ralston EJ, Gurling M, Schartner CM, Bian Q, Doudna JA, Meyer BJ  (2013-10)  Genetics  195(2), 331-348  "Precise and heritable genome editing in evolutionarily diverse nematodes using TALENs and CRISPR/Cas9 to engineer insertions and deletions."
  8. Pattanayak V, (Lin S), Guilinger JP, Ma E, Doudna JA, Liu DR  (2013-09)  Nature biotechnology  31(9), 839-843  "High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity."
  9. Jinek M, East A, Cheng A, (Lin S), Ma E, Doudna J  (2013-01)  eLife  2, e00471  "RNA-programmed genome editing in human cells."
  10. Agarwal V, (Lin S), Lukk T, Nair SK, Cronan JE  (2012-10)  Proceedings of the National Academy of Sciences of the United States of America  109(43), 17406-17411  "Structure of the enzyme-acyl carrier protein (ACP) substrate gatekeeper complex required for biotin synthesis."
  11. (Lin S), Cronan JE  (2012-10)  The Journal of biological chemistry  287(44), 37010-37020  "The BioC O-methyltransferase catalyzes methyl esterification of malonyl-acyl carrier protein, an essential step in biotin synthesis."
  12. Cronan JE, (Lin S)  (2011-06)  Current opinion in chemical biology  15(3), 407-413  "Synthesis of the alpha,omega-dicarboxylic acid precursor of biotin by the canonical fatty acid biosynthetic pathway."
  13. (Lin S), Hanson RE, Cronan JE  (2010-09)  Nature chemical biology  6(9), 682-688  "Biotin synthesis begins by hijacking the fatty acid synthetic pathway."