Institute of Biological Chemistry, Academia Sinica

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.

Degrees and Positions Held

• 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

• 2024 – present   Associate Research Fellow, Institute of Biological Chemistry, Academia Sinica, Taiwan
• 2016 – 2024   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

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)

Publication List