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.

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

1. 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."
   
2. 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"
   
3. 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."
   
4. 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."
   
5. 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."
   
6. 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."
   
7. (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."
   
8. 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."
   
9. 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."
   
10. 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."
    
11. Jinek M, East A, Cheng A, (Lin S), Ma E, Doudna J  (2013-01)  eLife  2, e00471  "RNA-programmed genome editing in human cells."
    
12. 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."
    
13. (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."
    
14. 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."
    
15. (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."