YOKOI YasuhiroAssistant Professor
- Laboratory
- Laboratory of Advanced Chemical Biology
- Research Theme
- Innovative drug discovery research targeting disease-specific aberrant glycosylation
- Research Keywords
Organic Chemistry, Chemical Biology, Glycotechnology, Medicinal Chemistry, Glycopeptide, Antibody Drug, Drug Delivery System
Overview of Research
Glycosylation, which is not encoded directly in the genome, has extremely complex structural diversity and various functions. In addition, structural abnormalities of glycans have been shown to be closely associated with the pathogenesis of many diseases including cancer. Recently, we have discovered that aberrant glycosylation in proteins alters the conformation of the core peptide backbone, resulting in the formation of disease-specific antigenic structure (epitope). This means that the conformational alteration of proteins caused by various glycosylation patterns are not only effective biomarkers for diagnosing the onset and progression of disease, but also promising as specific targets for therapeutic drugs. We are engaged in the discovery of disease-specific glycopeptide epitopes and the development of antibody drugs that recognize them, based on our world-leading technologies for chemical synthesis and structural analysis of glycans and glycopeptides.
Charge
- School of Science:
Biological Science course (Macromolecular Functions), Core Laboratories - Graduate School of Life Science:
Division of Life Science, Transdisciplinary Life Science Course, Biosystem and Biomolecule Control Science
Message
Glycans, known as the third life chain after genomic DNA and proteins, play important roles in various biological phenomena such as intercellular communication and immunity, however, many of the functions of glycans are still shrouded in mystery. We aim to elucidate the significance of glycosylation in the living body and develop new approaches for disease treatment, through the research focused on “the relationship between glycosylation and disease”.
Representative Publications
Murakami K., Kambe D., Yokoi Y., Wakui H., Hayakawa S., Hirane N., Koide R., Otaki M., Nagahori N., Nishimura S.-I., “Smart nanomedicine targeting endocytosis mediated by cancer cell surface neuraminidase-1”, Adv. Nanobiomed Res., 3, 2300076 (2023) https://doi.org/10.1002/anbr.202300076
Wakui H., Yokoi Y., Horidome C., Ose T., Yao M., Tanaka Y., Hinou H., Nishimura S.-I., “Structural and molecular insight into antibody recognition of dynamic neoepitopes in membrane tethered MUC1 of pancreatic cancer cells and secreted exosomes”, RSC Chem. Biol., 4, 564-572 (2023) https://doi.org/10.1039/D3CB00036B
Shiratori K., Yokoi Y., Wakui H., Hirane N., Otaki M., Hinou H., Yoneyama T., Hatakeyama S., Kimura S., Ohyama C., Nishimura S.-I., “Selective reaction monitoring approach using structure-defined synthetic glycopeptides for validating glycopeptide biomarkers pre-determined by bottom-up glycoproteomics”, RSC Adv., 12, 21385-21393 (2022) https://doi.org/10.1039/D2RA02903K
Koide R., Hirane N., Kambe D., Yokoi Y., Otaki M., Nishimura S.-I., “Antiadhesive nanosome elicits role of glycocalyx of tumor cell-derived exosomes in the organotropic cancer metastasis”, Biomaterials, 280, 121314 (2022) https://doi.org/10.1016/j.biomaterials.2021.121314
Yokoi Y., Nishimura S.-I., “Effect of site-specific O-glycosylation on the structural behavior of NOTCH1 receptor extracellular EGF-like domains 11 and 10”, Chem. Eur. J., 26, 12363-12372 (2020) https://doi.org/10.1002/chem.202002652
Hayakawa S., Matsushita T., Yokoi Y., Wakui H., Garcia-Martin F., Hinou H., Matsuoka K., Nouso K., Kamiyama T., Taketomi A., Nishimura S.-I., “Impaired O-glycosylation at consecutive threonine TTX motifs in mucins generates conformationally restricted cancer neoepitopes”, Biochemistry, 59, 1221-1241 (2020) https://doi.org/10.1021/acs.biochem.0c00007
Ohyabu N., Kakiya K., Yokoi Y., Hinou H., Nishimura S.-I., “Convergent solid-phase synthesis of macromolecular MUC1 models truly mimicking serum glycoprotein biomarkers of interstitial lung diseases”, J. Am. Chem. Soc., 138, 8392-8395 (2016) https://doi.org/10.1021/jacs.6b04973
Refer to HOKKAIDO UNIVERSITY RESEARCHERS DIRECTORY
Note
<Office Hour>
– Time: Anytime during the lecture period
– Place: Frontier-AMLS, 6F
Please contact in advance by E-mail.
E-mail: yasu[at]sci.hokudai.ac.jp
Affiliation
- Faculty of Advanced Life Science, Department of Advanced Transdisciplinary Sciences, Drug Discovery Research
- Frontier Research Center for Advanced Material and Life Science, Academia-Industry Collaboration Unit