研究領域與專長

CRISPR/Cas9系統是一套高效率基因改造技術平台，對於基因研究應用在人類細胞、動物和植物帶來突破性大變革。此系統的重要核心Cas9核酸內切酶是利用短片段guide RNA辨識目標DNA序列，並切割DNA造成雙股斷裂。藉由 Cas9 進行的雙股DNA 切割，使基因體定㸃斷裂，進而啟動細胞修補機制—非同源末端接合(Non-homologous end joining, NHEJ)和同源重組(Homology directed repair, HDR)。CRISPR/Cas9技術不僅能達成定㸃基因剔除, 剔入和基因修飾的目的，也開啟基因治療的契機。我們實驗室將發展更具有效率、精確和安全的CRISPR/Cas9系統，應用於人類基因組編輯。目前，我們的研究方向分為下列幾項：

  1. 開發多樣化CRISPR/Cas9應用系統
  2. 瞭解DNA修補機制如何有效啟動同源重組修復機制
  3. 研究Cas9蛋白進入細胞後對於基因轉錄調控的影響

歡迎對基因工程感興趣的學生們加入我們的研究團隊。

學經歷
經歷
  • 2016 – 迄今   助研究員, 中央研究院生物化學研究所
  • 2012 – 2015   博士後研究員, Department of Molecular and Cell Biology, University of California, Berkeley, USA
  • 2004 – 2004   研究助理, Department of Biochemistry, The Ohio State University, USA
  • 2001 – 2003   研究助理, 中央研究院化學研究所
學歷
  • 2006 – 2012   博士, 微生物系, 伊利諾大學香檳分校, 美國
  • 2004 – 2006   碩士, 生化系, 俄亥俄州立大學, 美國
  • 1996 – 2001   學士, 生物系, 英屬哥倫比亞大學, 加拿大
主要著作
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)
著作列表
  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."

CRISPR/Cas9系統是一套高效率基因改造技術平台，對於基因研究應用在人類細胞、動物和植物帶來突破性大變革。此系統的重要核心Cas9核酸內切酶是利用短片段guide RNA辨識目標DNA序列，並切割DNA造成雙股斷裂。藉由 Cas9 進行的雙股DNA 切割，使基因體定㸃斷裂，進而啟動細胞修補機制—非同源末端接合(Non-homologous end joining, NHEJ)和同源重組(Homology directed repair, HDR)。CRISPR/Cas9技術不僅能達成定㸃基因剔除, 剔入和基因修飾的目的，也開啟基因治療的契機。我們實驗室將發展更具有效率、精確和安全的CRISPR/Cas9系統，應用於人類基因組編輯。目前，我們的研究方向分為下列幾項：

  1. 開發多樣化CRISPR/Cas9應用系統
  2. 瞭解DNA修補機制如何有效啟動同源重組修復機制
  3. 研究Cas9蛋白進入細胞後對於基因轉錄調控的影響

歡迎對基因工程感興趣的學生們加入我們的研究團隊。

經歷
  • 2016 – 迄今   助研究員, 中央研究院生物化學研究所
  • 2012 – 2015   博士後研究員, Department of Molecular and Cell Biology, University of California, Berkeley, USA
  • 2004 – 2004   研究助理, Department of Biochemistry, The Ohio State University, USA
  • 2001 – 2003   研究助理, 中央研究院化學研究所
學歷
  • 2006 – 2012   博士, 微生物系, 伊利諾大學香檳分校, 美國
  • 2004 – 2006   碩士, 生化系, 俄亥俄州立大學, 美國
  • 1996 – 2001   學士, 生物系, 英屬哥倫比亞大學, 加拿大
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."