| Project/Area Number |
22K14548
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 27040:Biofunction and bioprocess engineering-related
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| Research Institution | Ritsumeikan University |
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Principal Investigator |
ABDALKADER Rodi 立命館大学, 立命館グローバル・イノベーション研究機構, 准教授 (20839964)
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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2022: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | Cornea-on-a-chip / Microfluidic / Metabolomic / Drug toxicity / cornea-on-a-chip / iPSC / metabolomics |
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| Outline of Research at the Start |
This proposal aims for the development of a dynamic human cornea model in integration with untargeted metabolomics by combining human induced pluripotent stem cells (iPSC), microfluidics technologies, and metabolomics. This approach will allow us to investigate the early toxicity of the ophthalmic drugs through the selection of significant metabolites markers upon drugs exposure.
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| Outline of Annual Research Achievements |
This research aims to identify metabolite markers related to drug toxicity using untargeted metabolomic analysis in a human corneal epithelium-on-a-chip. In the current fiscal year, we successfully investigated the adverse effects of a model drug, diclofenac, a non-steroidal anti-inflammatory drug, in the corneal epithelium-on-a-chip. Through the utilization of untargeted metabolomics and RNA sequencing, we were able to discover metabolite markers and relevant genes associated with diclofenac treatment, such as methyl-2-oxovaleric acid, 3-methyl-2-oxobutanoic acid, and lauroyl-carnitine. This untargeted metabolomic analysis approach in the corneal epithelium-on-a-chip has the potential to be further employed in combination with additional drugs in future.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
The advancement of this research can be credited to the effective implementation of an optimized untargeted metabolomic method for detecting extracellular metabolites in a corneal epithelium-on-a-chip model. Additionally, the capability to validate the system with a drug model has facilitated the discovery of new metabolite markers.
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| Strategy for Future Research Activity |
Based on current progress, we will initially investigate the function of the discovered metabolite markers to determine if they serve as toxic markers when tested with a larger set of drugs. Secondly, we will explore the sensitivity of these markers by examining their correlation with the early onset of relevant gene expression. Additionally, we will concentrate on employing human cells derived from human induced pluripotent stem cells (iPSCs).
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