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. Our research focuses on developing methods to enable robust, precise and safe genome manipulations in human genome. Current projects include:

  1. Genome engineering to enhance the immune functions of human natural killer cells for immunotherapy.
  2. Engineering of immune cell-specific adeno-associated virus to improve DNA delivery and CRISPR gene knock-in.
  3. Elucidating and alleviating the cellular stresses induced by CRISPR genome editing to improve editing precision and safety.

IBC website

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
A robust platform for expansion and genome editing of primary human natural killer cells.
Huang RS, Lai MC, Shih HA, Lin S*
J Exp Med. (2021)
Humanized COVID-19 decoy antibody effectively blocks viral entry and prevents SARS-CoV-2 infection.
Huang KY, Lin MS, Kuo TC, Chen CL, Lin CC, Chou YC, Chao TL, Pang YH, Kao HC, Huang RS, Lin S, Chang SY, Yang PC
EMBO Mol Med. (2021)
Hsc70/Stub1 promotes the removal of individual oxidatively stressed peroxisomes.
Chen BH, Chang YJ, Lin S, Yang WY
Nat Commun. (2020)
A multiplexed bioluminescent reporter for sensitive and non-invasive tracking of DNA double strand break repair dynamics in vitro and in vivo.
Chien JC, Tabet E, Pinkham K, da Hora CC, Chang JC, Lin S, Badr CE, Lai CP
Nucleic acids research (2020)
Enhanced NK-92 Cytotoxicity by CRISPR Genome Engineering Using Cas9 Ribonucleoproteins.
Huang RS, Shih HA, Lai MC, Chang YJ, Lin S*
Frontiers in Immunology (2020)
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)
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)
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)
Biotin synthesis begins by hijacking the fatty acid synthetic pathway.
Lin S, Hanson RE & Cronan JE
Nat. Chem. Biol. (2010)
Publications List
  1. Yang TJ, Li TN, Huang RS, Pan MY, Lin SY, (Lin S), Wu KP, Wang LH, Hsu STD*  (2022-06)  JOURNAL OF CELL BIOLOGY  221(6), e202201094  "Tumor suppressor BAP1 nuclear import is governed by transportin-1."
  2. Lin CS, Hsu CT, Yuan YH, Zheng PX, Wu FH, Cheng QW, Wu YL, Wu TL, (Lin S), Yue JJ, Cheng YH, Lin SI, Shih MC, Sheen J, Lin YC*  (2022-04)  Plant physiology  188(4), 1917-1930  "DNA-free CRISPR-Cas9 gene editing of wild tetraploid tomato Solanum peruvianum using protoplast regeneration."
  3. Hsu CT, Yuan YH, Lin YC, (Lin S), Cheng QW, Wu FH, Sheen J, Shih MC, Lin CS  (2021-10)  The CRISPR journal  4(5), 752-760  "Efficient and Economical Targeted Insertion in Plant Genomes via Protoplast Regeneration."
  4. Huang RS, Lai MC, (Lin S)*  (2021-09)  Current protocols  1(9), e246  "Ex Vivo Expansion and CRISPR-Cas9 Genome Editing of Primary Human Natural Killer Cells."
  5. Hsieh HH, Chen YA, Chang YJ, Wang HH, Yu YH, Lin SW, Huang YJ, (Lin S), Chang CJ*  (2021-06)  Journal of Inflammation-London  18(1), 22  "The functional characterization of phosphorylation of tristetraprolin at C-terminal NOT1-binding domain."
  6. Chen CL, Chen YC, Huang WL, (Lin S), Daugelavicius R, Rapoport A, Chang CR  (2021-04)  International Journal of Molecular Sciences  22(9), 4607  "A Crucial Role of Mitochondrial Dynamics in Dehydration Resistance in Saccharomyces cerevisiae."
  7. Huang RS, Lai MC, Shih HA, (Lin S)*  (2021-03)  J Exp Med.  218(3), e20201529  "A robust platform for expansion and genome editing of primary human natural killer cells."
  8. Huang KY, Lin MS, Kuo TC, Chen CL, Lin CC, Chou YC, Chao TL, Pang YH, Kao HC, Huang RS, (Lin S), Chang SY, Yang PC  (2021-01)  EMBO Mol Med.  13(1), e12828  "Humanized COVID-19 decoy antibody effectively blocks viral entry and prevents SARS-CoV-2 infection."
  9. Chen BH, Chang YJ, (Lin S), Yang WY  (2020-10)  Nature Communications  11(1), 5267  "Hsc70/Stub1 promotes the removal of individual oxidatively stressed peroxisomes."
  10. Chien JC, Tabet E, Pinkham K, da Hora CC, Chang JC, (Lin S), Badr CE, Lai CP  (2020-09)  Nucleic acids research  48(17), e100  "A multiplexed bioluminescent reporter for sensitive and non-invasive tracking of DNA double strand break repair dynamics in vitro and in vivo."
  11. Huang RS, Shih HA, Lai MC, Chang YJ, (Lin S)*  (2020-05)  Frontiers in Immunology  11, 1008  "Enhanced NK-92 Cytotoxicity by CRISPR Genome Engineering Using Cas9 Ribonucleoproteins"
  12. 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."
  13. 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."
  14. 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."
  15. 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."
  16. (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."
  17. 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."
  18. 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."
  19. 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."
  20. Jinek M, East A, Cheng A, (Lin S), Ma E, Doudna J  (2013-01)  eLife  2, e00471  "RNA-programmed genome editing in human cells."
  21. 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."
  22. (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."
  23. 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."
  24. (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. Our research focuses on developing methods to enable robust, precise and safe genome manipulations in human genome. Current projects include:

  1. Genome engineering to enhance the immune functions of human natural killer cells for immunotherapy.
  2. Engineering of immune cell-specific adeno-associated virus to improve DNA delivery and CRISPR gene knock-in.
  3. Elucidating and alleviating the cellular stresses induced by CRISPR genome editing to improve editing precision and safety.

IBC website

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
A robust platform for expansion and genome editing of primary human natural killer cells.
Huang RS, Lai MC, Shih HA, Lin S*
J Exp Med. (2021)
Humanized COVID-19 decoy antibody effectively blocks viral entry and prevents SARS-CoV-2 infection.
Huang KY, Lin MS, Kuo TC, Chen CL, Lin CC, Chou YC, Chao TL, Pang YH, Kao HC, Huang RS, Lin S, Chang SY, Yang PC
EMBO Mol Med. (2021)
Hsc70/Stub1 promotes the removal of individual oxidatively stressed peroxisomes.
Chen BH, Chang YJ, Lin S, Yang WY
Nat Commun. (2020)
A multiplexed bioluminescent reporter for sensitive and non-invasive tracking of DNA double strand break repair dynamics in vitro and in vivo.
Chien JC, Tabet E, Pinkham K, da Hora CC, Chang JC, Lin S, Badr CE, Lai CP
Nucleic acids research (2020)
Enhanced NK-92 Cytotoxicity by CRISPR Genome Engineering Using Cas9 Ribonucleoproteins.
Huang RS, Shih HA, Lai MC, Chang YJ, Lin S*
Frontiers in Immunology (2020)
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)
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)
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)
Biotin synthesis begins by hijacking the fatty acid synthetic pathway.
Lin S, Hanson RE & Cronan JE
Nat. Chem. Biol. (2010)
  1. Yang TJ, Li TN, Huang RS, Pan MY, Lin SY, (Lin S), Wu KP, Wang LH, Hsu STD*  (2022-06)  JOURNAL OF CELL BIOLOGY  221(6), e202201094  "Tumor suppressor BAP1 nuclear import is governed by transportin-1."
  2. Lin CS, Hsu CT, Yuan YH, Zheng PX, Wu FH, Cheng QW, Wu YL, Wu TL, (Lin S), Yue JJ, Cheng YH, Lin SI, Shih MC, Sheen J, Lin YC*  (2022-04)  Plant physiology  188(4), 1917-1930  "DNA-free CRISPR-Cas9 gene editing of wild tetraploid tomato Solanum peruvianum using protoplast regeneration."
  3. Hsu CT, Yuan YH, Lin YC, (Lin S), Cheng QW, Wu FH, Sheen J, Shih MC, Lin CS  (2021-10)  The CRISPR journal  4(5), 752-760  "Efficient and Economical Targeted Insertion in Plant Genomes via Protoplast Regeneration."
  4. Huang RS, Lai MC, (Lin S)*  (2021-09)  Current protocols  1(9), e246  "Ex Vivo Expansion and CRISPR-Cas9 Genome Editing of Primary Human Natural Killer Cells."
  5. Hsieh HH, Chen YA, Chang YJ, Wang HH, Yu YH, Lin SW, Huang YJ, (Lin S), Chang CJ*  (2021-06)  Journal of Inflammation-London  18(1), 22  "The functional characterization of phosphorylation of tristetraprolin at C-terminal NOT1-binding domain."
  6. Chen CL, Chen YC, Huang WL, (Lin S), Daugelavicius R, Rapoport A, Chang CR  (2021-04)  International Journal of Molecular Sciences  22(9), 4607  "A Crucial Role of Mitochondrial Dynamics in Dehydration Resistance in Saccharomyces cerevisiae."
  7. Huang RS, Lai MC, Shih HA, (Lin S)*  (2021-03)  J Exp Med.  218(3), e20201529  "A robust platform for expansion and genome editing of primary human natural killer cells."
  8. Huang KY, Lin MS, Kuo TC, Chen CL, Lin CC, Chou YC, Chao TL, Pang YH, Kao HC, Huang RS, (Lin S), Chang SY, Yang PC  (2021-01)  EMBO Mol Med.  13(1), e12828  "Humanized COVID-19 decoy antibody effectively blocks viral entry and prevents SARS-CoV-2 infection."
  9. Chen BH, Chang YJ, (Lin S), Yang WY  (2020-10)  Nature Communications  11(1), 5267  "Hsc70/Stub1 promotes the removal of individual oxidatively stressed peroxisomes."
  10. Chien JC, Tabet E, Pinkham K, da Hora CC, Chang JC, (Lin S), Badr CE, Lai CP  (2020-09)  Nucleic acids research  48(17), e100  "A multiplexed bioluminescent reporter for sensitive and non-invasive tracking of DNA double strand break repair dynamics in vitro and in vivo."
  11. Huang RS, Shih HA, Lai MC, Chang YJ, (Lin S)*  (2020-05)  Frontiers in Immunology  11, 1008  "Enhanced NK-92 Cytotoxicity by CRISPR Genome Engineering Using Cas9 Ribonucleoproteins"
  12. 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."
  13. 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."
  14. 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."
  15. 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."
  16. (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."
  17. 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."
  18. 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."
  19. 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."
  20. Jinek M, East A, Cheng A, (Lin S), Ma E, Doudna J  (2013-01)  eLife  2, e00471  "RNA-programmed genome editing in human cells."
  21. 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."
  22. (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."
  23. 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."
  24. (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."