Spatiotemporal metabolomics analysis in the human cornea-on-a-chip for the determination of ocular drug toxicity
| 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, 助教 (20839964)
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Project Status |
Granted (Fiscal Year 2022)
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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, an untargeted metabolic workflow that we previously developed was utilized to analyze extracellular metabolites in human induced pluripotent stem cells (hiPSCs) under early differentiation conditions. A total of 117 metabolites were successfully annotated in a small sample volume of one microliter. This optimized untargeted metabolomic method will be applied to the human corneal epithelium-on-a-chip in the next phase of the study.
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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 progress of this research can be attributed to the successful optimization of the untargeted metabolomic method for detecting extracellular metabolites in both corneal epithelial cells and hiPSCs. Additionally, the establishment of functional corneal epithelial cells from hiPSCs will further facilitate the investigation of drug toxicity in the corneal epithelium-on-a-chip model with greater precision and accuracy.
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| Strategy for Future Research Activity |
To investigate changes in extracellular metabolites, the untargeted metabolomic method optimized in the previous stage will be applied in the human corneal epithelium-on-a-chip under drug treatment.
In parallel, changes in gene expression under drug treatment will also be investigated. This will be done using transcriptomic analysis to identify differentially expressed genes in response to drug treatment.
Finally, to validate the relationship between changes in extracellular metabolites and gene expression, correlation analysis will be performed to identify any significant associations between the two. These results will provide a more comprehensive understanding of drug toxicity related metabolite markers and their underlying mechanisms.
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Report
(1 results)
Research Products
(4 results)
