YOSUKE HASHIMOTO

Last Updated :2025/05/09

E-mail
hashimoyhiroshima-u.ac.jp
Self-introduction
I am an assistant professor in Prof. Yasuo Uchida lab in Hiroshima University. I received my Ph.D (pharmacology) in Osaka University in Japan and I have completed postdoctoral training in Prof. Matthew Campbell lab in Trinity College Dublin. My research interests are CLDN5 gene and claudin-5 protein in the blood-brain barrier. The function and expression level of claudin-5 are critical in determining the onset/frequency/severeness of a range of neurological diseases, especially epilepsy, psychiatric disorders and cognitive decline. I have developed anti-claudin-5 monoclonal antibodies that can disturb the junctional localization of claudin-5 by steric inhibition. Added to this, I have discovered a novel pathogenic CLDN5 missense mutation that causes alternating hemiplegia of childhood with epilepsy and brain stem calcification. We discovered this mutant creates anion-permeable tight junctions by converting the barrier forming function of claudin-5. I'd like to develop drugs that can control claudin-5 expression/function to treat abnormal claudin-5 related neurological diseases.

Basic Information

Major Professional Backgrounds

  • 2024/07, Hiroshima University Graduate School of Biomedical and Health Sciences, Molecular Systems Pharmaceutics, Assistant Professor
  • 2022/10, 2024/06, Trinity College Dublin, Smurfit Institute of Genetics, Post-Doc Researcher
  • 2020/04, 2022/09, Japan Society for the Promotion of Science, JSPS Overseas Research Fellow
  • 2019/07, 2022/09, Trinity College Dublin, Smurfit Institute of Genetics, Visiting Researcher
  • 2017/04, 2020/03, Japan Society for the Promotion of Science, JSPS Post-Doctoral Research Fellow (PD)
  • 2017/04, 2019/06, Nagoya University, Research Institute of Environmental Medicine, Research Fellow
  • 2015/04, 2017/03, Japan Society for the Promotion of Science, JSPS Research Fellow (DC2)

Educational Backgrounds

  • Osaka University, Graduate School of Pharmaceutical Science, Japan, 2014/04, 2017/03
  • The University of Tokushima, Graduate School of Pharmaceutical Technosciences, Japan, 2012/04, 2014/03
  • The University of Tokushima, Faculty of Pharmaceutical Sciences, School of Pharmaceutical Technosciences, Japan, 2008/04, 2012/03

Academic Degrees

  • The University of Tokushima
  • Osaka University

Research Keywords

  • Blood-brain barrier
  • Tight junction
  • Claudin-5
  • Monoclonal antibody

Affiliated Academic Societies

  • International Brain Barriers Society (IBBS)

Educational Activity

Course in Charge

  1. 2025, Undergraduate Education, 3Term, Introduction to Pharmaceutical Sciences
  2. 2025, Undergraduate Education, First Semester, Practice of Drug Delivery System
  3. 2025, Undergraduate Education, 4Term, Industrial Pharmaceutics
  4. 2025, Undergraduate Education, 3Term, Japanese Pharmacopoeia
  5. 2025, Undergraduate Education, First Semester, Practice of Pharmaceutics
  6. 2025, Undergraduate Education, Year, Special laboratory Works in Pharmaceutical Sciences I
  7. 2025, Undergraduate Education, Year, Special laboratory Works in Pharmaceutical Sciences II
  8. 2025, Undergraduate Education, Second Semester, Special laboratory Works in Pharmaceutical Sciences III
  9. 2025, Undergraduate Education, Year, Special laboratory Works in Clinical Pharmacy I
  10. 2025, Undergraduate Education, Year, Special laboratory Works in Clinical Pharmacy II
  11. 2025, Undergraduate Education, Year, Special laboratory Works in Clinical Pharmacy III
  12. 2025, Graduate Education (Doctoral Program) , First Semester, Advanced Seminar on Molecular Systems Pharmaceutics
  13. 2025, Graduate Education (Doctoral Program) , Second Semester, Advanced Seminar on Molecular Systems Pharmaceutics
  14. 2025, Graduate Education (Doctoral Program) , First Semester, Advanced Research on Molecular Systems Pharmaceutics
  15. 2025, Graduate Education (Doctoral Program) , Second Semester, Advanced Research on Molecular Systems Pharmaceutics
  16. 2025, Graduate Education (Doctoral Program) , Second Semester, Advanced Research in Pharmaceutical Science
  17. 2025, Graduate Education (Master's Program) , First Semester, Seminar on Drug Delivery Sciences
  18. 2025, Graduate Education (Master's Program) , Second Semester, Seminar on Drug Delivery Sciences
  19. 2025, Graduate Education (Master's Program) , First Semester, Seminar on Molecular Systems Pharmaceutics
  20. 2025, Graduate Education (Master's Program) , Second Semester, Seminar on Molecular Systems Pharmaceutics
  21. 2025, Graduate Education (Master's Program) , First Semester, Advanced Research on Molecular Systems Pharmaceutics
  22. 2025, Graduate Education (Master's Program) , Second Semester, Advanced Research on Molecular Systems Pharmaceutics
  23. 2025, Graduate Education (Doctoral Program) , First Semester, Advanced Seminar on Molecular Systems Pharmaceutics
  24. 2025, Graduate Education (Doctoral Program) , Second Semester, Advanced Seminar on Molecular Systems Pharmaceutics
  25. 2025, Graduate Education (Doctoral Program) , First Semester, Advanced Research on Molecular Systems Pharmaceutics
  26. 2025, Graduate Education (Doctoral Program) , Second Semester, Advanced Research on Molecular Systems Pharmaceutics

Research Activities

Academic Papers

  1. Key Claudins at the Blood-Retina Barriers, Advances in experimental medicine and biology, 1468, 447-451, 202502
  2. Enhanced retinal pigment epithelial cells as a delivery vehicle for retinal disease, Molecular Therapy Methods & Clinical Development, 33(2), 101450, 202506
  3. Eyes on glutamate in angiogenesis and barrier formation., Neuron, 112(12), 2024
  4. ★, Pumilio-1 mediated translational control of claudin-5 at the blood-brain barrier, Fluids and Barriers of the CNS, 21, 52, 20240619
    Link to Paper Search Results by DOI
  5. A loss of function mutation in CLDN25 causing Pelizaeus-Merzbacher-like leukodystrophy, Human Molecular Genetics, 20240317
    Link to Paper Search Results by DOI
  6. Reply: De novo mutations in CLDN5: alternating hemiplegia of childhood or not?, Brain : a journal of neurology, 146(8), 2023
  7. ★, The CLDN5 gene at the blood-brain barrier in health and disease., Fluids and barriers of the CNS, 20(1), 2023
    Link to Paper Search Results by DOI
  8. ★, Recurrent de novo mutations in CLDN5 induce an anion-selective blood–brain barrier and alternating hemiplegia, Brain, 145(10), 3374-3382, 20221021
    Link to Paper Search Results by DOI
  9. Claudin-5: A Pharmacological Target to Modify the Permeability of the Blood-Brain Barrier., Biological & pharmaceutical bulletin, 44(10), 2021
    Link to Paper Search Results by DOI
  10. Safety and efficacy of an anti-claudin-5 monoclonal antibody to increase blood–brain barrier permeability for drug delivery to the brain in a non-human primate, Journal of Controlled Release, 336, 105-111, 202108
    Link to Paper Search Results by DOI
  11. Tight junction modulation at the blood-brain barrier: Current and future perspectives., Biochimica et biophysica acta. Biomembranes, 1862(9), 2020
    Link to Paper Search Results by DOI
  12. Tight junction modulators for drug delivery to the central nervous system., Drug discovery today, 25(8), 2020
  13. Potential for Tight Junction Protein-Directed Drug Development Using Claudin Binders and Angubindin-1., International journal of molecular sciences, 20(16), 2019
  14. Anti-Claudin Antibodies as a Concept for Development of Claudin-Directed Drugs., The Journal of pharmacology and experimental therapeutics, 368(2), 2019
  15. A Novel Platform for Cancer Vaccines: Antigen-Selective Delivery to Splenic Marginal Zone B Cells via Repeated Injections of PEGylated Liposomes., Journal of immunology (Baltimore, Md. : 1950), 201(10), 2969-2976, 20181115
  16. A Cell Assay for Detecting Anti-PEG Immune Response against PEG-Modified Therapeutics., Pharmaceutical research, 35(11), 223-223, 20181002
  17. A hydroxyl PEG version of PEGylated liposomes and its impact on anti-PEG IgM induction and on the accelerated clearance of PEGylated liposomes., European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 127, 142-149, 201806
  18. Safety evaluation of a human chimeric monoclonal antibody that recognizes the extracellular loop domain of claudin-2., European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 117, 161-167, 20180530
  19. Engineered membrane protein antigens successfully induce antibodies against extracellular regions of claudin-5., Scientific reports, 8(1), 8383-8383, 20180530
    Link to Paper Search Results by DOI
  20. Roles of the first-generation claudin binder, Clostridium perfringens enterotoxin, in the diagnosis and claudin-targeted treatment of epithelium-derived cancers., Pflugers Archiv : European journal of physiology, 469(1), 2017
  21. Claudin-targeted drug development using anti-claudin monoclonal antibodies to treat hepatitis and cancer., Annals of the New York Academy of Sciences, 1397(1), 2017
  22. ★, Claudin-5-Binders Enhance Permeation of Solutes across the Blood-Brain Barrier in a Mammalian Model., The Journal of pharmacology and experimental therapeutics, 363(2), 275-283, 201711
    Link to Paper Search Results by DOI
  23. Efficacy and safety evaluation of claudin-4-targeted antitumor therapy using a human and mouse cross-reactive monoclonal antibody., Pharmacology research & perspectives, 4(5), e00266, 201610
  24. Generation and characterization of a human-mouse chimeric antibody against the extracellular domain of claudin-1 for cancer therapy using a mouse model., Biochemical and biophysical research communications, 477(1), 91-95, 20160812
  25. Gene Silencing Using 4'-thioDNA as an Artificial Template to Synthesize Short Hairpin RNA Without Inducing a Detectable Innate Immune Response., Molecular therapy. Nucleic acids, 5, e274, 20160105
  26. Current progress in a second-generation claudin binder, anti-claudin antibody, for clinical applications., Drug discovery today, 21(10), 2016
  27. Anti-PEG IgM and complement system are required for the association of second doses of PEGylated liposomes with splenic marginal zone B cells., Immunobiology, 220(10), 1151-60, 201510
  28. Anti-PEG IgM Is a Major Contributor to the Accelerated Blood Clearance of Polyethylene Glycol-Conjugated Protein., Molecular pharmaceutics, 12(7), 2429-35, 20150706
  29. Comprehensive analysis of PEGylated liposome-associated proteins relating to the accelerated blood clearance phenomenon by combination with shotgun analysis and conventional methods, Biotechnology and Applied Biochemistry, 62(4), 547-555, 201507
  30. Relationship between the concentration of anti-polyethylene glycol (PEG) immunoglobulin M (IgM) and the intensity of the accelerated blood clearance (ABC) phenomenon against PEGylated liposomes in mice., Biological & pharmaceutical bulletin, 38(3), 417-24, 2015
  31. Chemistry, properties, and in vitro and in vivo applications of 2'-O-methoxyethyl-4'-thioRNA, a novel hybrid type of chemically modified RNA., Chembiochem : a European journal of chemical biology, 15(17), 2535-40, 20141124
  32. B cell-intrinsic toll-like receptor 7 is responsible for the enhanced anti-PEG IgM production following injection of siRNA-containing PEGylated lipoplex in mice., Journal of controlled release : official journal of the Controlled Release Society, 184, 1-8, 20140628
  33. Activation of TLR9 by incorporated pDNA within PEG-coated lipoplex enhances anti-PEG IgM production., Gene therapy, 21(6), 593-8, 201406
  34. Generation, characterization and in vivo biological activity of two distinct monoclonal anti-PEG IgMs., Toxicology and applied pharmacology, 277(1), 30-8, 20140515

Invited Lecture, Oral Presentation, Poster Presentation

  1. Not only ATP1A3 mutations: a novel de novo CLDN5 missense mutation found in two independent AHC patients., Yosuke Hashimoto, Natalie Hudson, Nathalie Boddaer, Arnold Munnich, Matthew Campbell, 12th Symposium on ATP1A3 in Disease, 2024/11/15, Without Invitation, English
  2. CLDN5 Missense Mutations in Neurological Diseases, Yosuke Hashimoto, Gordon Research Conference on Barriers of the CNS, 2024/06/10, With Invitation, English
  3. Identification of novel negative regulators of blood retina barrier integrity by genome-wide screening; Relevance to novel treatments for age-related macular degeneration, Yosuke Hashimoto; Natalie Hudson; Gergő Porkoláb; Jeffrey O'Callaghan; Nicole Hanley; Chris Greene; Masuo Kondoh; Mária Deli; Matthew Campbell, XXth INTERNATIONAL SYMPOSIUM ON RETINAL DEGENERATION RD2023, Without Invitation, English
  4. A novel de novo missense mutation in CLDN5 found in patients with alternating hemiplegia of childhood, Yosuke Hashimoto; Chris Greene; Karine Poirier; Nathalie Boddaer; Laurence Huber; Melodie Aubar; Isabelle Desguerre; Arnold Munnich; Matthew Campbell, 5th Mini-symposium on the blood-brain barrier From basic to clinical research, 2023/03/03, With Invitation, English
  5. Discovery of a novel pathogenic de novo CLDN5 mutation associated with alternating hemiplegia of childhood, Yosuke Hashimoto, 12th UK and Ireland Early Career BBB Symposium, 2022/10/27, Without Invitation, English
  6. Functional analysis of a novel pathogenic de novo CLDN5 mutation asscoiated with alternating hemiplegia, Yosuke Hashimoto, Karine Poirier, Nathalie Boddaert, Laurence Hubert, Melodie Aubart, Isabelle Desguerre, Arnold Munnich, Matthew Campbell, 24th International symposium on signal transduction at the blood–brain barriers, Without Invitation, English
  7. Pumilios-mediated translational control of claudin-5, Yosuke Hashimoto; Chris Greene; Conor Delaney; Natalie Hudson; Matthew Campbell, Gordon Research Seminar/Conference, Barriers of the CNS, Without Invitation, English
  8. Development of Claudin-5 Modulators and Evaluation of Their In Vitro Permeation-Activity of Solutes across the Blood-Brain Barrier in a Mammalian Model, Yosuke Hashimoto; Keisuke Shirakura; Yoshiaki Okada; Hiroyuki Takeda; Akihiro Watari; Tatsuya Sawasaki; Keisuke Tachibana; Takefumi Doi; Kiyohito Yagi; Masuo Kondoh, SOT2020 59th Annual Meeting & ToxExpo, Without Invitation, English
  9. Claudin-5 as a target for drug delivery to the brain by modulation blood-brain barrier, Masuo Kondoh; Yosuke Hashimoto; Keisuke Shirakura; Yoshiaki Okada; Hiroyuki Takeda; Kohki Endo; Maki Tamura; Akihiro Watari; Yoshifusa Sadamura; Tatsuya Sawasaki; Keisuke Tachibna; Takefumi Doi; Kiyohito Yagi, Experimental Biology 2019, Without Invitation, English
  10. Safety evaluation of a human chimeric monoclonal antibody that recognizes the extracellular loop domain of claudin-2, Yosuke Hashimoto; Tomoyuki Hata; Minoru Tada; Manami Iida; Akihiro Watari; Yoshiaki Okada; Takefumi Doi; Hiroki Kuniyasu; Kiyohito Yagi; Masuo Kondoh, EUROTOX2018, Without Invitation, English
  11. Safety profile and anti-tumor activity of a new generated human/mouse cross-reactive anti-claudin-4 monoclonal antibody in mice, Yosuke Hashimoto; Yumi Kawahigashi; Tomoyuki Hata; Xiangru Li; Kiyohito Yagi; Masuo Kondoh, European Cancer Congress (ECCO) 2015, Without Invitation, English

Awards

  1. 2023/10, A Travel Award to the RD2023 meeting, The XXth International Symposium on Retinal Degenerations (RD2023) and the BrightFocus Macular Fast Track
    Related URL
  2. 2014/01, Kohraku award (good student award), The University of Tokushima
  3. 2013/11, Best Presentation Award, 35th symposium of biomembrane-drug interactions
  4. 2012/05, A scholarship from Nagai foundation, Nagai memorial foundation

Patented

  1. Patent, JP第6900051号, Claudin 5 antibody and medicament containing the antibody
  2. Patent, JP第7108956号, Anti-CLDN-5 antibody, and drug containing said antibody

External Funds

Acceptance Results of Competitive Funds

  1. Research Grant, Revealing the pathogenic mechanisms of hemiplegia induced by a missense mutation in claudin-5, 2025, 2026
  2. Research Grant, Prediction of the brain distribution of OTC drugs in individuals with lower claudin-5 expression level, 2025, 2026
  3. Research Grant, Stabilizing endothelial tight junctions to develop novel therapeutic strategies for anti-VEGF–resistant diabetic macular edema, 2025, 2026
  4. Bilateral Joint Seminars, The first knowledge exchange between Korean MPS engineers and Japanese barriologists ; For developing novel in vitro blood-neural interfaces with real physiological barriers., 2025, 2025
  5. Open Partnership, Joint Research Projects, Tightened IE-JP: development of new barrier enhancers for neural vasculatures by sta bilizing Inter-Endothelial Junctional Proteins via a novel regulatory pathway, 2025, 2027
  6. Grant-in-Aid for Scientific Research(C), Integrative multi-omics to reveal the expression/localization patterns of RNAs/proteins in the blood-brain barrier, 2025, 2028
  7. An internal competitive research grant for researches focused on infection diseases, A preliminary study to ameliorate long COVID syndrome-associated brain fog by improving the blood-brain barrier integrity, 2024, 2025
  8. New Foundations, strand 2, Genome-wide screening to discover novel claudin-5 regulating genes for establishing the strategy to normalize the permeability of blood-brain barrier, 2020/07, 2021/03
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  9. KAKENHI for Young Researcher, Visualization of gene expression around the blood-brain barrier by keeping spatial information, 2019/04/01, 2020/03/31
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  10. Research Grant for JSPS Post-doctoral Research Fellow, The development of a novel strategy to modulate the blood-brain barrier permeability by tight-junction binders, 2017/04/26, 2020/03/31
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  11. Research Grant (donation-type), The development of a novel strategy to modulate the blood-brain barrier by anti-claudin-5 antibody, 2019/04, 2020/03
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  12. Research Grant for JSPS Research Fellow, The development of claudin-5 binders for drug delivery into the brain, 2015/04/24, 2017/03/31
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