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Horisawa Kenichi Last modified date:2021.06.28

Assistant Professor / Division of Organogenesis and Regeneration
Department of Molecular and Cellular Biology
Medical Institute of Bioregulation




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Homepage
https://kyushu-u.pure.elsevier.com/en/persons/kenichi-horisawa
 Reseacher Profiling Tool Kyushu University Pure
Academic Degree
Ph.D
Country of degree conferring institution (Overseas)
No
Field of Specialization
Molecular Biology, Biochemistry
Total Priod of education and research career in the foreign country
00years00months
Research
Research Interests
  • Analysis of the relationship between liver regeneration and metabolism
    keyword : Liver, Regeneration, Metabolism
    2018.08~2020.07.
  • Crosstalk between lipid metabolism and transcription
    keyword : lipid metabolism, transcription
    2016.04~2019.03.
  • Molecular elucidation of liver development and direct reprogramming of somatic cells to hepatocyte
    keyword : liver,organogenesis, direct reprogramming, epigenetics, proteomics
    2013.12~2018.11.
Academic Activities
Books
1. Noriko Tabata, Horisawa Kenichi, Hiroshi Yanagawa, “Chapter 4: Applications of the In Vitro Virus (IVV) Method for Various Protein Functional Analyses” Protein Engineering - Technology and Application, InTech, pp.85-110, 2013.05.
2. Horisawa Kenichi, Hiroshi Yanagawa, “Chapter 10: Musashi Proteins in Neural Stem/Progenitor Cells” Neural Stem Cells and Therapy, InTech, pp.205-222, 2012.02.
Reports
1. Kenichi Horisawa, Atsushi Suzuki, Direct cell-fate conversion of somatic cells: Toward regenerative medicine and industries, Proceedings of the Japan Academy, Ser. B, Physical and Biological Sciences, https://doi.org/10.2183/pjab.96.012, 2020.04, Cells of multicellular organisms have diverse characteristics despite having the same genetic identity. The distinctive phenotype of each cell is determined by molecular mechanisms such as epigenetic changes that occur throughout the lifetime of an individual. Recently, technologies that enable modification of the fate of somatic cells have been developed, and the number of studies using these technologies has increased drastically in the last decade. Various cell types, including neuronal cells, cardiomyocytes, and hepatocytes, have been generated using these technologies. Although most direct reprogramming methods employ forced transduction of a defined sets of transcription factors to reprogram cells in a manner similar to induced pluripotent cell technology, many other strategies, such as methods utilizing chemical compounds and microRNAs to change the fate of somatic cells, have also been developed. In this review, we summarize transcription factor-based reprogramming and various other reprogramming methods. Additionally, we describe the various industrial applications of direct reprogramming technologies..
2. Horisawa Kenichi, Atsushi SUZUKI, Cell-Based Regenerative Therapy for Liver Disease, Innovative Medicine Basic Research and Development, Springer, 2015.10.
3. 堀澤 健一, Specific and quantitative labeling of biomolecules using click chemistry., Front Physiol., 2014.11.
4. Horisawa Kenichi, Takao Imai, Hideyuki Okano, Hiroshi Yanagawa, The Musashi family RNA-binding proteins in stem cells, Biomolecular Concepts, 2010.03.
Papers
1. Inada H., Udono M., Matsuda-Ito K., Horisawa K., Ohkawa Y., Miura S., Goya T., Yamamoto J., Nagasaki M., Ueno K., Saitou D., Suyama M., Maehara Y., Kumamaru W., Ogawa Y., Sekiya S., Suzuki A., Direct reprogramming of human umbilical vein- and peripheral blood-derived endothelial cells into hepatic progenitor cells., Nat comm, 10.1038/s41467-020-19041-z, 11, 5292, 2020.12, Recent advances have enabled the direct induction of human tissue-specific stem and pro- genitor cells from differentiated somatic cells. However, it is not known whether human hepatic progenitor cells (hHepPCs) can be generated from other cell types by direct lineage reprogramming with defined transcription factors. Here, we show that a set of three tran- scription factors, FOXA3, HNF1A, and HNF6, can induce human umbilical vein endothelial cells to directly acquire the properties of hHepPCs. These induced hHepPCs (hiHepPCs) propagate in long-term monolayer culture and differentiate into functional hepatocytes and cholangiocytes by forming cell aggregates and cystic epithelial spheroids, respectively, under three-dimensional culture conditions. After transplantation, hiHepPC-derived hepatocytes and cholangiocytes reconstitute damaged liver tissues and support hepatic function. The defined transcription factors also induce hiHepPCs from endothelial cells circulating in adult human peripheral blood. These expandable and bipotential hiHepPCs may be useful in the study and treatment of human liver diseases..
2. Horisawa K., Udono M., Ueno K., Ohkawa Y., Nagasaki M., Sekiya S., Suzuki A., The Dynamics of Transcriptional Activation by Hepatic Reprogramming Factors., Mol Cell, 10.1016/j.molcel.2020.07.012, 79, 660-676, 2020.08, Specific combinations of two transcription factors (Hnf4a plus Foxa1, Foxa2, or Foxa3) can induce direct conversion of mouse fibroblasts into hepatocyte-like cells. However, the molecular mechanisms underlying hepatic reprogramming are largely unknown. Here, we show that the Foxa protein family members and Hnf4a sequentially and cooperatively bind to chromatin to activate liver-specific gene expression. Although all Foxa proteins bind to and open regions of closed chromatin as pioneer factors, Foxa3 has the unique potential of transferring from the distal to proximal regions of the transcription start site of target genes, binding RNA polymerase II, and co-traversing target genes. These distinctive characteristics of Foxa3 are essential for inducing the hepatic fate in fibroblasts. Similar functional coupling of transcription factors to RNA polymerase II may occur in other contexts whereby transcriptional activation can induce cell differentiation..
3. Terada, Maiko; Kawamata, Masaki; Kimura, Ryota; Sekiya, Sayaka; Nagamatsu, Go; Hayashi, Katsuhiko; Horisawa, Kenichi; Suzuki, Atsushi, Generation of Nanog reporter mice that distinguish pluripotent stem cells from unipotent primordial germ cells, GENESIS, 10.1002/dvg.23334, 57, 11-12, 2019.11.
4. Takashima Y, Horisawa K, Udono M, Ohkawa Y, Suzuki A., Prolonged inhibition of hepatocellular carcinoma cell proliferation by combinatorial expression of defined transcription factors., Cancer Sci., 10.1111/cas.13798., 109, 11, 3543-3553, 2018.11.
5. Maiko Terada, Horisawa K, Shizuka Miura, 高島 康郎, Ohkawa, Y, Sayaka Sekiya, 松田 花菜江, Atsushi Suzuki, Kupffer cells induce Notch-mediated hepatocyte conversion in a common mouse model of intrahepatic cholangiocarcinoma., Sci Rep., doi: 10.1038/srep34691., 6, 34691-34691, 2016.10, Intrahepatic cholangiocarcinoma (ICC) is a malignant epithelial neoplasm composed of cells resembling cholangiocytes that line the intrahepatic bile ducts in portal areas of the hepatic lobule. Although ICC has been defined as a tumor arising from cholangiocyte transformation, recent evidence from genetic lineage-tracing experiments has indicated that hepatocytes can be a cellular origin of ICC by directly changing their fate to that of biliary lineage cells. Notch signaling has been identified as an essential factor for hepatocyte conversion into biliary lineage cells at the onset of ICC. However, the mechanisms underlying Notch signal activation in hepatocytes remain unclear. Here, using a mouse model of ICC, we found that hepatic macrophages called Kupffer cells transiently congregate around the central veins in the liver and express the Notch ligand Jagged-1 coincident with Notch activation in pericentral hepatocytes. Depletion of Kupffer cells prevents the Notch-mediated cell-fate conversion of hepatocytes to biliary lineage cells, inducing hepatocyte apoptosis and increasing mortality in mice. These findings will be useful for uncovering the pathogenic mechanism of ICC and developing prevenient and therapeutic strategies for this refractory disease..
6. Niikura K, Horisawa K, Doi N, Endosomal escape efficiency of fusogenic B18 and B55 peptides fused with anti-EGFR single chain Fv as estimated by nuclear translocation., J Biochem., 10.1093/jb/mvv083., 159, 1, 123-132, 2016.01.
Presentations
1. Kenichi Horisawa, Shizuka Miura, Yoshihiro Izumi, Takeshi Bamba, Atsushi Suzuki, Trans-omic analysis for metabolic remodeling during liver regeneration, The 29th Hot Spring Harbor International Symposium, 2020.02, The liver is the central metabolic organ that produces energy for life activities and detoxifies various extrinsic and intrinsic harmful substances. Also, the liver is one of the organs capable of regeneration. After deletion of two-thirds of the total liver mass, the remaining liver tissue immediately enlarge and recover hepatic function. Remodeling of the metabolic process in the injured liver is a candidate of the responsible mechanism regulating liver regeneration. It is known that the concentration of various metabolites from the central metabolic pathways affects cellular states through the extensive epigenetic change of chromatin. Also, several metabolites including a group of lipid-derived molecules eicosanoids are known to work as signal mediators for cell proliferation. Moreover, because regenerative potential of the liver attenuates in the aging process, comparison of the regenerating livers between young and old mice could elucidate the molecular mechanism of liver regeneration. Thus, in this study, we performed a metabolomic analysis using liver samples obtained from young and old mice before and after the partial hepatectomy to elucidate the molecular machinery and discover the key metabolites regulating liver regeneration. In addition, we performed a trans-omic analysis using our metabolome data and a public transcriptome data set obtained from the regenerating liver. We present the data in this symposium and hope a lively discussion..
Membership in Academic Society
  • Japanese proteomics society
  • The RNA society of Japan
  • The molecular Biology society of Japan
Educational
Educational Activities
Research advising for students
Other Educational Activities
  • 2014.06, Research advising for 3rd grade students in medical school.
  • 2015.06, Research advising for 3rd grade students in medical school.
  • 2016.06, Research advising for 3rd grade students in medical school
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  • 2017.06, Research advising for 3rd grade students in medical school.
  • 2018.06, Research advising for 3rd grade students in medical school
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  • 2019.06, Research advising for 3rd grade students in medical school
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  • 2020.06, Research advising for 3rd grade students in medical school
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  • 2021.06, Research advising for 3rd grade students in medical school
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