Kyushu University Academic Staff Educational and Research Activities Database
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Hiroaki Takesue Last modified date:2023.07.04

Undergraduate School

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Academic Degree
Ph.D. (Pharmaceutical Science)
Country of degree conferring institution (Overseas)
Field of Specialization
Genome science, Molecular biology, Epigenetics, Pharmacokinetics
ORCID(Open Researcher and Contributor ID)
Total Priod of education and research career in the foreign country
Research Interests
  • Knockout of RTT109 accelerates expansion of CUP1 arrays in budding yeast
    keyword : Saccharomyces cerevisiae, CUP1, Cas9, histone modification, copy number variation
  • Understanding the expansion mechanism of tandem repeats by a novel method using Cas9 nickase
    keyword : Saccaromyces cerevisiae, tandem repeat, CUP1, Cas9, copy number variation
Academic Activities
1. Takeshi Hirota, Toshihiro Tanaka, Hiroaki Takesue, Ichiro Ieiri, Epigenetic regulation of drug transporter expression in human tissues, Expert Opinion on Drug Metabolism and Toxicology,, 2017.01, Introduction: Drug transporters are expressed in a number of tissues such as the intestine, liver, and kidney, and play key roles in drug absorption, distribution, and excretion. Variations in drug transporter gene expression significantly contribute to interindividual differences in drug responses. Epigenetic regulation of drug transporter genes has recently emerged as an important mechanism. Epigenetic regulation alters the expression of genes without changing DNA sequences. Epigenetic control mechanisms are associated with DNA methylation, histone modifications, and microRNAs. Herein we discuss recent advances in the study of the transcriptional and post-transcriptional mechanisms of drug transporters with a focus on epigenetic regulation. Areas covered: This review summarizes recent research on the epigenetic regulation of drug transporter genes, and highlights the importance of identifying novel biomarkers based on epigenetics for use in individualized drug therapy. Expert opinion: Researchers are actively attempting to elucidate the epigenetic mechanisms that control the expression of drug transporters, which affect the pharmacokinetics of drugs. Current evidence suggests that epigenetic changes play an important role in drug transporter function. A clearer understanding of epigenetic regulation in drug transporter genes will provide an insight into novel approaches to individualized drug therapy..
Membership in Academic Society
  • The Japan Society for Epigenetics
  • Japan Society of Bioscience, Biotechnology, and Agrichemistry
  • The Molecular Biology Society of Japan
  • Molecular mechanisms of gene amplification are diverse, and most remain elusive. Accordingly, the application of gene amplification to construct stable gene expression systems is insufficient. We have developed a novel gene amplification method “BiTREx” based on a defined molecular mechanism that is controllable and does not require selection pressure, using budding yeast as a model. BiTREx stems from the fact that a nick introduced by Cas9 nickase causes replisome disassembly to generate a single-end double-strand break to be repaired by break-induced replication. Suppose the replisome that has just replicated the target tandem repeat encounters a nick at its flanking site. In that case, BIR should frequently initiate thorough non-allelic single-strand DNA invasion to expand the tandem repeat. Indeed, BiTREx successfully expanded a CUP1 array consisting of 16 copies of 2 kb repeat units to ~500 repeat units (~1 Mb). Furthermore, BiTREx successfully expanded not only another natural tandem gene array (ENA1 array) but artificial ones consisting of ~10-kb repeat units inserted at the CUP1 locus. Thus, BiTREx is a versatile method to enable various novel applications in synthetic genomics. We will also show a seamless system for gene integration followed by BiTREx in this symposium, and present the possibility of applying gene amplification by BiTREx to various researches.