Shengdar Tsai, PhD
Shengdar Q. Tsai, PhD

Shengdar Q. Tsai, PhD

Assistant Member, St. Jude Faculty




BS – University of Michigan
MS – North Carolina State University
PhD – North Carolina State University
Fellowship – Harvard Medical School / Massachusetts General Hospital

Research Interests

  • Genome Engineering
    • Improving genomic methods to define and measure gene editing “off-target” effects
    • Protein engineering of CRISPR-Cas nucleases for precise gene correction
    • Regulation of DNA damage repair choice between error-prone non-homologous end-joining and precise homology-directed repair
  • Hematology
    • Genome-scale CRISPR-Cas screening for novel effectors of hematological diseases
    • Developing novel strategies for allele-specific editing of genetic mutations that cause sickle cell disease and other hematological disorders

Selected Publications

Full list of publications

Lazzarotto CR, Nguyen NT, Tang X, Malagon-Lopez J, Guo JA, Aryee MJ, Joung JK, Tsai SQ. Defining CRISPR-Cas9 genome-wide nuclease activities with CIRCLE-seq. Nat Protoc October, 2018.

Kim MY, Yu K, Kenderian SS, Ruella M, Chen S, Shin T, Aljanahi A, Schreeder D, Klichinsky M, Shestov O, Kozlowski MS, Cummin KD, Shan X, Shestov M, Bagg A, Morrissette JJD, Sekhri P, Lazzarotto CR, Calvo KR, Kuhns DB, Donahue RE, Behbehani GK, Tsai SQ, Dunbar CE, Gill S. Genetic Inactivation of CD33 in Hematopoietic Stem Cells to Enable CAR T Cell Immunotherapy for Acute Myeloid Leukemia. Cell May 2018.

Tsai SQ§, Nguyen NT, Malagon-Lopez J, Topkar VV, Aryee MJ, Joung JK§. CIRCLE-seq: a highly sensitive in vitro screen for genome-wide CRISPR-Cas9 nuclease off-targets. Nat Methods May 2017. §Co-corresponding author.

Kleinstiver BP*, Tsai SQ*, Prew MS, Nguyen NT, Welch MM, Lopez JM, McCaw ZR, Aryee MJ, Joung JK. Genome-wide specificity profile of CRISPR-Cas Cpf1 nucleases in human cells. Nat Biotechnol June, 2016. *Equal contribution co-first author.

Tsai SQ, Topkar VV, Joung JK, Aryee MJ. guideseq: open-source software for analysis of GUIDE-seq data. Nat Biotechnol May 2016.

Kleinstiver BP, Pattanayak V, Prew MS, Tsai SQ, Nguyen NT, Zheng Z, Joung JK. High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature January 2016.

Kleinstiver BP, Prew MS, Tsai SQ, Nguyen NT, Topkar VV, Zheng Z, Joung JK. Broadening Staphylococcus aureus Cas9 Targeting Range by Modifying PAM Recognition. Nat Biotechnol  November 2015.

Hubbard BP, Badran AH, Zuris JA, Guilinger JP, Davis KM, Chen L, Tsai SQ, Sander JD, Joung JK, Liu DR. Continuous directed evolution of DNA-binding proteins to improve TALEN specificity. Nat Methods August 2015.

Kleinstiver BP, Prew MS, Tsai SQ, Topkar VV, Nguyen NT, Zheng Z, Gonzales APW, Li Z, Peterson RT, Yeh J-RJ, Aryee MJ, Joung JK. Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature July 2015.

Wyvekens N, Topkar VV, Khayter C, Joung JK§, Tsai SQ§. Dimeric CRISPR RNA-guided FokIdCas9 nucleases (RFNs) directed by truncated gRNAs for highly specific genome editing. Hum Gene Ther July 2015. §Co-corresponding author.

Liao J, Karnik R, Gu H, Ziller MJ, Clement K, Tsankov AM, Akopian V, Gifford CA, Donaghey J, Galonska C, Pop R, Reyon D, Tsai SQ, Mallard W, Joung JK, Rinn JL, Gnirke A, Meissner A. Targeted disruption of DNMT1, DNMT3A and DNMT3B in human embryonic stem cells. Nat Genet May 2015.

Tsai SQ*§, Zheng Z*, Nguyen NT, Liebers M, Topkar VV, Thapar V, Wyvekens N, Khayter C, Iafrate AJ, Le LP, Aryee MJ, Joung JK§. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nat Biotechnol February 2015. *Equal contribution co-first author. §Co-corresponding author.

Hill SJ, Rolland T, Adelmant G, Xia X, Owen MS, Dricot A, Zack TI, Sahni N, Jacob Y, Hao T, McKinney KM, Clark AP, Reyon D, Tsai SQ, Joung JK, Beroukhim R, Marto JA, Vidal M, Gaudet S, Hill DE, Livingston DM. Systematic screening reveals a role for BRCA1 in the response to transcription-associated DNA damage. Genes and Development September 2014.

Tsai SQ, Wyvekens N, Khayter C, Foden JA, Thapar V, Reyon D, Goodwin MJ, Aryee MJ, Joung JK. Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing. Nat Biotechnol June 2014.

Guilinger JP, Pattanayak V, Reyon D, Tsai SQ, Sander JD, Joung JK, Liu DR. Broad specificity profiling of TALENs results in engineered nucleases with improved DNA-cleavage specificity. Nat Methods April 2014.

Pauli A, Norris ML, Valen E, Chew GL, Gagnon JA, Zimmerman S, Mitchell A, Ma J, Dubrulle J, Reyon D, Tsai SQ, Joung JK, Saghatelian A, Schier AF. Toddler: An Embryonic Signal That Promotes Cell Movement via Apelin Receptors. Science January 2014.

Low BE, Krebs MP, Joung JK, Tsai SQ, Nishina PM, Wiles MV. Correction of the Crb1rd8 allele and retinal phenotype in C57BL/6N mice via TALEN-mediated homology-directed repair. Invest Ophthalmol Vis Sci December 2013.

Maeder ML, Angstman JF, Richardson ME, Linder SJ, Cascio VM, Tsai SQ, Ho QH, Sander JD, Reyon D, Bernstein BE, Costello JF, Wilkinson MF, Joung JK. Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins. Nat Biotechnol October 2013.

Guo L, Tsai SQ, Hardison NE, James AH, Motsinger-Reif AA, Thames B, Stone EA, Deng C, Piedrahita JA. Differentially expressed microRNAs and affected biological pathways revealed by modulated modularity clustering (MMC) analysis of humanpreeclamptic and IUGR placentas. Placenta July 2013.

Hwang WY, Fu Y, Reyon D, Maeder ML, Tsai SQ, Sander JD, Peterson RT, Yeh JR, Joung JK. Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat Biotechnol March 2013.

Bischoff SR, Tsai SQ, Hardison NE, Motsinger-Reif AA, Freking BA, Nonneman DJ, Rohrer GA, Piedrahita JA. Differences in X-chromosome transcriptional activity and cholesterol metabolism between placentae from swine breeds from Asian and Western origins. PLoS One January 2013.

Koh S, Thomas R, Tsai S, Bischoff S, Lim, JH, Breen M, Olby NJ, Piedrahita JA. Growth requirements and chromosomal instability of induced pluripotent stem cells (iPSC) generated from adult canine fibroblasts. Stem Cells Dev September 27, 2012.

Cade L, Reyon D, Hwang WY, Tsai SQ, Patel S, Khayter C, Joung JK, Sander JD, Peterson RT, Yeh JR. Highly efficient generation of heritable zebrafish gene mutations using homo- and heterodimeric TALENs. Nucleic Acids Research June 7, 2012.

Reyon D*, Tsai SQ*, Khayter C., Foden JA, Sander JD, Joung JK. FLASH assembly of TALENs for high-throughput genome editing. Nature Biotechnology May 30, 2012. *Equal contribution co-first author.

Chung J, Tsai S, James AH, Thames BH, Shytle S, Piedrahita JA. Lack of genomic imprinting of DNA primase, polypeptide 2 (PRIM2) in human term placenta and white blood cells. Epigenetics May 2012.

Tsai S*, Hardison NE*, James AH, Motsinger-Reif AA, Bischoff SR, Thames B, Piedrahita JA. Transcriptional profiling of human placentas from pregnancies complicated by preeclampsia reveals disregulation of sialic acid acetylesterase and immune signalling pathways. Placenta February 6, 2011. *Equal contribution co-first author.

Bischoff SR*, Tsai S*, Hardison N, Motsinger-Reif AA, Freking BA, Nonneman D, Rohrer G, Piedrahita JA. Characterization of conserved and nonconserved imprinted genes in swine. Biology of Reproduction November 2009. *Equal contribution co-first author.

Estrada JL, Collins B, York A, Bischoff S, Sommer J, Tsai S, Petters RM, Piedrahita JA. Successful cloning of the yucatan minipig using commercial/occidental breeds as oocyte donors and embryo recipients. Cloning Stem Cells June 2008.

Bischoff SR*, Tsai S*, Hardison N, York A, Freking BA, Nonneman D, Rohrer G, Piedrahita JA. Identification of SNPs and INDELS in swine transcribed sequences using short oligonucleotide microarrays. BMC Genomics May 2008. *Equal contribution co-first author.

Tsai S, Mir B, Martin AC, Estrada JL, Bischoff SR, Hsieh WP, Cassady JP, Freking BA, Nonneman DJ, Rohrer GA, Piedrahita JA. Detection of transcriptional difference of porcine imprinted genes using different microarray platforms. BMC Genomics December 2006.

Last update: October 2018