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Yoshida Yuya Last modified date:2022.09.22

Assistant Professor / Department of Clinical Pharmacokinetics
Department of Pharmaceutical Health Care and Sciences
Faculty of Pharmaceutical Sciences

Graduate School

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Academic Degree
Pharmacy, Ph.D
Country of degree conferring institution (Overseas)
Field of Specialization
ORCID(Open Researcher and Contributor ID)
Outline Activities
Various circadian rhythms (circadian rhythms) with one cycle of 24 hours are recognized in our bodily functions, such as sleep-wake cycles and hormone secretion. These rhythms are caused by a group of genes called clock genes. The rhythms in the expression and function of various molecules in the body play an extremely important role in maintaining homeostasis in the body. When these rhythms are disrupted, the onset of disease and the efficacy of medications are adversely affected. We are analyzing the effects of abnormalities in circadian rhythms during disease on the progression of disease and the efficacy of drugs, with the aim of constructing more efficient treatments and developing completely new therapies.
Research Interests
  • Analysis of the mechanism of pathological deterioration of chronic kidney disease based on circadian clock mechanism
    keyword : Chronic kidney disease, clock genes, circadian clock mechanism
Academic Activities
1. Akito Tsuruta,Yuki Shiiba,Naoya Matsunaga,Marina Fujimoto,Yuya Yoshida,Satoru Koyanagi,Shigehiro Ohdo, Diurnal Expression of PD-1 on Tumor-Associated Macrophages Underlies the Dosing Time-Dependent Antitumor Effects of the PD-1/PD-L1 Inhibitor BMS-1 in B16/BL6 Melanoma-Bearing Mice, Molecular Cancer Research, 10.1158/1541-7786.MCR-21-0786., 20(6):972-982, 2022.06, Cancer cells have acquired several pathways to escape from host immunity in the tumor microenvironment. Programmed death 1 (PD-1) receptor and its ligand PD-L1 are involved in the key pathway of tumor immune escape, and immune checkpoint therapy targeting PD-1 and PD-L1 has been approved for the treatment of patients with certain types of malignancies. Although PD-1 is a well-characterized receptor on T cells, the immune checkpoint receptor is also expressed on tumor-associated macrophages (TAM), a major immune component of the tumor microenvironment. In this study, we found significant diurnal oscillation in the number of PD-1-expressing TAMs collected from B16/BL6 melanoma-bearing mice. The levels of Pdcd1 mRNA, encoding PD-1, in TAMs also fluctuated in a diurnal manner. Luciferase reporter and bioluminescence imaging analyses revealed that a NF-κB response element in the upstream region of the Pdcd1 gene is responsible for its diurnal expression. A circadian regulatory component, DEC2, whose expression in TAMs exhibited diurnal oscillation, periodically suppressed NF-κB-induced transactivation of the Pdcd1 gene, resulting in diurnal expression of PD-1 in TAMs. Furthermore, the antitumor efficacy of BMS-1, a small molecule inhibitor of PD-1/PD-L1, was enhanced by administering it at the time of day when PD-1 expression increased on TAMs. These findings suggest that identification of the diurnal expression of PD-1 on TAMs is useful for selecting the most appropriate time of day to administer PD-1/PD-L1 inhibitors..