Dr Kosuke Yusa | Group Leader

Kosuke develops and applies novel genome engineering techniques in mouse and human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells to screen for disease-causing variations. His group's recent focus has been on development of genome-wide CRISPR-based genetic screening and its applications in stem cell and oncology research.

Kosuke graduated from Osaka University in 1999 with a BSc in Bioengineering and completed an MSc in Agricultural science in 2001 at the University of Tokyo. In 2005, he obtained his PhD from Osaka University under the supervision of Professor Junji Takeda and received the 'Yamamura prize' (Graduate Student of the Year). As part of his PhD, Kosuke established a novel forward genetic screening method in mouse ES cells that uses the hyper-recombination phenotype of Bloom helicase-deficient cells.

After his PhD, he was awarded a post-doctoral fellowship from the Japan Society of Promotion of Science and joined Professor Allan Bradley's team at the Sanger Institute in 2007. He has developed the hyperactive piggyBac 'jumping gene' (DNA transporter system) and used it to create a novel platform of iPS cell reprogramming. By combining this system with zinc finger nuclease technology, he has achieved highly precise genetic correction of disease-causing mutations in human iPS cells, opening the way to new clinical treatments.

In October 2012, Kosuke was appointed as a member of the Sanger Institute Faculty in the newly developed scientific programme, Cellular Genetics.

Publications

  • Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library.

    Koike-Yusa H, Li Y, Tan EP, Velasco-Herrera Mdel C and Yusa K

    Nature biotechnology 2014;32;3;267-73

  • Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells.

    Yusa K, Rashid ST, Strick-Marchand H, Varela I, Liu PQ et al.

    Nature 2011;478;7369;391-4

  • Generation of transgene-free induced pluripotent mouse stem cells by the piggyBac transposon.

    Yusa K, Rad R, Takeda J and Bradley A

    Nature methods 2009;6;5;363-9

  • Genome-wide phenotype analysis in ES cells by regulated disruption of Bloom's syndrome gene.

    Yusa K, Horie K, Kondoh G, Kouno M, Maeda Y et al.

    Nature 2004;429;6994;896-9

  • A CRISPR Dropout Screen Identifies Genetic Vulnerabilities and Therapeutic Targets in Acute Myeloid Leukemia.

    Tzelepis K, Koike-Yusa H, De Braekeleer E, Li Y, Metzakopian E et al.

    Cell reports 2016;17;4;1193-1205

  • Mutational History of a Human Cell Lineage from Somatic to Induced Pluripotent Stem Cells.

    Rouhani FJ, Nik-Zainal S, Wuster A, Li Y, Conte N et al.

    PLoS genetics 2016;12;4;e1005932

  • piggyBac Transposon.

    Yusa K

    Microbiology spectrum 2015;3;2;MDNA3-0028-2014

  • Off-target assessment of CRISPR-Cas9 guiding RNAs in human iPS and mouse ES cells.

    Tan EP, Li Y, Velasco-Herrera Mdel C, Yusa K and Bradley A

    Genesis (New York, N.Y. : 2000) 2015;53;2;225-36

  • Removal of reprogramming transgenes improves the tissue reconstitution potential of keratinocytes generated from human induced pluripotent stem cells.

    Igawa K, Kokubu C, Yusa K, Horie K, Yoshimura Y et al.

    Stem cells translational medicine 2014;3;9;992-1001

  • Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library.

    Koike-Yusa H, Li Y, Tan EP, Velasco-Herrera Mdel C and Yusa K

    Nature biotechnology 2014;32;3;267-73

  • Seamless genome editing in human pluripotent stem cells using custom endonuclease-based gene targeting and the piggyBac transposon.

    Yusa K

    Nature protocols 2013;8;10;2061-78

  • Enhancement of microhomology-mediated genomic rearrangements by transient loss of mouse Bloom syndrome helicase.

    Yamanishi A, Yusa K, Horie K, Tokunaga M, Kusano K et al.

    Genome research 2013;23;9;1462-73

  • Nuclear Wave1 is required for reprogramming transcription in oocytes and for normal development.

    Miyamoto K, Teperek M, Yusa K, Allen GE, Bradshaw CR and Gurdon JB

    Science (New York, N.Y.) 2013;341;6149;1002-5

  • A genetic progression model of Braf(V600E)-induced intestinal tumorigenesis reveals targets for therapeutic intervention.

    Rad R, Cadiñanos J, Rad L, Varela I, Strong A et al.

    Cancer cell 2013;24;1;15-29

  • The piggyBac transposon displays local and distant reintegration preferences and can cause mutations at noncanonical integration sites.

    Li MA, Pettitt SJ, Eckert S, Ning Z, Rice S et al.

    Molecular and cellular biology 2013;33;7;1317-30

  • Hyperactive piggyBac gene transfer in human cells and in vivo.

    Doherty JE, Huye LE, Yusa K, Zhou L, Craig NL and Wilson MH

    Human gene therapy 2012;23;3;311-20

  • The critical role of histone H2A-deubiquitinase Mysm1 in hematopoiesis and lymphocyte differentiation.

    Nijnik A, Clare S, Hale C, Raisen C, McIntyre RE et al.

    Blood 2012;119;6;1370-9

  • Mobilization of giant piggyBac transposons in the mouse genome.

    Li MA, Turner DJ, Ning Z, Yusa K, Liang Q et al.

    Nucleic acids research 2011;39;22;e148

  • A homozygous mutant embryonic stem cell bank applicable for phenotype-driven genetic screening.

    Horie K, Kokubu C, Yoshida J, Akagi K, Isotani A et al.

    Nature methods 2011;8;12;1071-7

  • Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells.

    Yusa K, Rashid ST, Strick-Marchand H, Varela I, Liu PQ et al.

    Nature 2011;478;7369;391-4

  • Interhomolog recombination and loss of heterozygosity in wild-type and Bloom syndrome helicase (BLM)-deficient mammalian cells.

    LaRocque JR, Stark JM, Oh J, Bojilova E, Yusa K et al.

    Proceedings of the National Academy of Sciences of the United States of America 2011;108;29;11971-6

  • A hyperactive piggyBac transposase for mammalian applications.

    Yusa K, Zhou L, Li MA, Bradley A and Craig NL

    Proceedings of the National Academy of Sciences of the United States of America 2011;108;4;1531-6

  • PiggyBac transposon mutagenesis: a tool for cancer gene discovery in mice.

    Rad R, Rad L, Wang W, Cadinanos J, Vassiliou G et al.

    Science (New York, N.Y.) 2010;330;6007;1104-7

  • Butyrate greatly enhances derivation of human induced pluripotent stem cells by promoting epigenetic remodeling and the expression of pluripotency-associated genes.

    Mali P, Chou BK, Yen J, Ye Z, Zou J et al.

    Stem cells (Dayton, Ohio) 2010;28;4;713-20

  • Fezf1 is required for penetration of the basal lamina by olfactory axons to promote olfactory development.

    Watanabe Y, Inoue K, Okuyama-Yamamoto A, Nakai N, Nakatani J et al.

    The Journal of comparative neurology 2009;515;5;565-84

  • Generation of transgene-free induced pluripotent mouse stem cells by the piggyBac transposon.

    Yusa K, Rad R, Takeda J and Bradley A

    Nature methods 2009;6;5;363-9

  • Sleeping beauty transposase has an affinity for heterochromatin conformation.

    Ikeda R, Kokubu C, Yusa K, Keng VW, Horie K and Takeda J

    Molecular and cellular biology 2007;27;5;1665-76

  • Rad54 is dispensable for the ALT pathway.

    Akiyama K, Yusa K, Hashimoto H, Poonepalli A, Hande MP et al.

    Genes to cells : devoted to molecular & cellular mechanisms 2006;11;11;1305-15

  • Sleeping beauty transposon-based phenotypic analysis of mice: lack of Arpc3 results in defective trophoblast outgrowth.

    Yae K, Keng VW, Koike M, Yusa K, Kouno M et al.

    Molecular and cellular biology 2006;26;16;6185-96

  • Bloom's syndrome gene-deficient phenotype in mouse primary cells induced by a modified tetracycline-controlled trans-silencer.

    Hayakawa T, Yusa K, Kouno M, Takeda J and Horie K

    Gene 2006;369;80-9

  • Region-specific saturation germline mutagenesis in mice using the Sleeping Beauty transposon system.

    Keng VW, Yae K, Hayakawa T, Mizuno S, Uno Y et al.

    Nature methods 2005;2;10;763-9

  • Genome-wide phenotype analysis in ES cells by regulated disruption of Bloom's syndrome gene.

    Yusa K, Horie K, Kondoh G, Kouno M, Maeda Y et al.

    Nature 2004;429;6994;896-9

  • Enhancement of Sleeping Beauty transposition by CpG methylation: possible role of heterochromatin formation.

    Yusa K, Takeda J and Horie K

    Molecular and cellular biology 2004;24;9;4004-18

  • Characterization of Sleeping Beauty transposition and its application to genetic screening in mice.

    Horie K, Yusa K, Yae K, Odajima J, Fischer SE et al.

    Molecular and cellular biology 2003;23;24;9189-207

Yusa, Kosuke
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Kosuke's Timeline
2012

Group Leader at the Wellcome Trust Sanger Institute

2007

Postdoctoral fellow at the Wellcome Trust Sanger Institute

2005

PhD awarded by Osaka University Graduate School of Medicine

2001

Master digree awarded by the University of Tokyo Graduate School of Agricultural and Life Sciences

1999

Bachelor digree awarded by Osaka University Fuculty of Engineering