| Project/Area Number |
19K23837
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0803:Pathology, infection/immunology, and related fields
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| Research Institution | Hokkaido University |
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Principal Investigator |
Yoo Ji-Seung 北海道大学, 医学研究院, 助教 (30843437)
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| Project Period (FY) |
2019-08-30 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | GVHD / MHC class I / NLRC5 / Molecular target / Therapeutics / Therapeutic target / Organ transplantation / CD8 T cell / Inflammation / BMT / MHC I |
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| Outline of Research at the Start |
GVHD is caused by alloreactive donor T cells, which result in multi-organ system dysfunction and destruction, however currently no effective therapeutics is available. The goal of my study is to provide a rationale for targeting NLRC5 as a potential novel therapeutic for GVHD treatment.
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| Outline of Final Research Achievements |
Graft-versus-host disease (GVHD) is an unfavorable side effect of the allo-HSCT and a major limitation for the treatment of leukemia patients. However, currently, there are no effective medications available. The goal of my project was 1) to understand the underlying mechanism of the development of GVHD, 2) identify a molecular target involved in the disease onset, and 3) develop a novel therapeutic approach. During 2 years, I focused on the MHC class I pathway that is critically associated with disease onset and pathogenesis and achieved my research goals. I clarified that NLRC5, a master transactivator of the MHC class I pathway plays a critical role in the GVHD pathogenesis. Depletion of NLRC5 genes using the mouse model showed improved clinical outcomes. These findings will provide a novel idea for the development of GVHD therapeutics.
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| Academic Significance and Societal Importance of the Research Achievements |
Organ transplantation recipients develop severe GVHD. However, current treatments are limited with strong side effects. More importantly, those drugs do not fundamentally cure the disease. My study contributes to the current science field and society by providing a novel therapeutic target for GVHD.
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