Ph.D. Professor Kosuke Yusa
A variety of genes are involved in every biological process. Identifying these genes and understanding their biological functions are the basis of biology and clinical translation of research outcome. Applying genome editing technologies, our laboratory developed a powerful forward genetic screening method – CRISPR screening – and has provided toolkits to the research community. Our current research aims to understand the molecular mechanisms underlying proliferation and differentiation of cancer and pluripotent stem cells using CRISPR screening, and develop novel therapeutic applications.
Research and Education
To understand gene functions using genetics, we aim to identify the causal relationship between phenotype and genotype. While reverse genetics conducts phenotypic analysis of mutants of a gene of choice, forward genetics provides a powerful mean to comprehensively identify genes involved in a phenotype of interest. However, methods available for studies in mammalian cells were not as high as hoped. To overcome this limitation, we applied CRISPR-Cas9 systems and developed powerful ‘CRISPR screening’. Our current interest is to understand the molecular mechanism by which cancer and pluripotent stem cells proliferate and differentiate, and we take advantage of our CRISPR screen technique to address new biological questions. In recent years, we increasingly focus on hematological malignancy. Among factors identified, we investigate the molecular mechanisms of those that have potentials for clinical application. For pluripotent stem cells, we are particularly interested in regulatory networks that governs differentiation of human ES/iPS cell line. Understanding the mechanisms would allow us to develop robust differentiation protocols and facilitate the translation of pluripotent cell technologies.
Figure 1. Workflow of CRISPR screening
A mutant cell library can be subjected to various type of phenotypic analysis.
Figure 2. Colorectal cancer cell lines
Each cell line shows distinct morphology. By screening these cell lines, we identified that the WRN gene is specifically required for cells with microsatellite instability.
Recent Publications
- Aoki K, Hyuga M, Tarumoto Y, Nishibuchi G, Ueda A, Ochi Y, Sugino S, Mikami T, Kobushi H, Kato I, Akahane K, Inukai T, Takaori-Kondo A, Takita J, Ogawa S and Yusa K. Canonical BAF complex regulates the oncogenic program in human T-cell acute lymphoblastic leukemia. Blood 143:604-618 (2024)
- Ishikawa M, Sugino S, Masuda Y, Tarumoto Y, Seto Y, Taniyama N, Wagai F, Yamauchi Y, Kojima Y, Kiryu H, Yusa K, Eiraku M and Mochizuki A. RENGE infers gene regulatory networks using time-series single-cell RNA-seq data with CRISPR perturbations. Commun Biol. 6:1290 (2023)
- Behan FM, Iorio F, Picco G, Goncalves E, Beaver CM, Migliardi G, Santos R, Rao Y, Sassi F, Pinnelli M, Ansari R, Harper S, Jackson DA, McRae R, Pooley R, Wilkinson P, Meer D, Dow D, Buser-Doepner C, Bertotti A, Trusolino L, Stronach EA, Saez-Rodriguez J, Yusa K and Garnett MJ. Prioritisation of oncology therapeutic targets using CRISPR-Cas9 screening. Nature 568:511-516 (2019)
- Au YZ, Gu M, De Braekeleer E, Gozdecka M, Aspris D, Tarumoto Y, Cooper J, Yu J, Ong SH, Chen X, Tzelepis K, Huntly BJP, Vassiliou G and Yusa K. KAT7 is a genetic vulnerability of acute myeloid leukemias driven by MLL rearrangements. Leukemia 35:1012-1022 (2021)
- Koike-Yusa H, Li Y, Tan EP, Velasco-Herrera MD and Yusa K. Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library. Nature Biotechnol. 32:267-273 (2014)
Laboratory
Professor: Dr Kosuke Yusa
Assistant Professor: Dr Yusuke Tarumoto
Assistant Professor: Dr Gohei Nishibuchi
Assistant Professor: Dr Kazunari Aoki
TEL: +81 75 751 4100
Email: k.yusa@infront.kyoto-u.ac.jp