The recent advance of induced pluripotent stem cell (iPSC) technology holds great promise to overcome many limitations of conventional approaches to studying neurodevelopment and neurodegenerative diseases. One key advantage to iPSCs is the ability to conduct in vitro studies in which neural differentiation and disease progression can be both directed and monitored. Since iPSCs can be generated from patients, these cells may serve as a powerful tool to better understand human neurodegenerative disease on a molecular, cellular or even tissue/organ level.
Taking advantage of iPSC, genome editing and organoid technology for CNS neurodevelopment and neurodegenerative disease modeling, we aim to understand the mechanism underlining brain degeneration and regeneration, in hope to develop strategy to treat neurodegenerative disease. Specifically, our research focus on 1. Functional role of the non-coding RNAs in human CNS degeneration and regeneration through iPSC-based disease modeling. 2. Pluripotent stem cell-based human CNS engineering through 3D organoid and assembloid technology. 3. Human iPSC-based immunotherapy and gene therapy platforms for CNS disorders and cancers.
Wu YY and Kuo HC* (2020) Functional roles and networks of non-coding RNAs in the pathogenesis of neurodegenerative diseases, Journal of Biomedical Science, 27(1):49
Huang HP, Chiang W, Chuang CY, Stone L, Kang CK, Hwu WL, Kuo HC*. (2019) Using human Pompe Disease induced pluripotent stem cells-derived neural cells for identifying chemicals with therapeutic potential. Molecular Human Genetics, 28(23):3880-3894
Yu CY, Li TC, Wu YY, Yeh CH, Chiang W, Chuang CY, Kuo HC*. (2017) The Circular RNA circBIRC6 participates in the molecular circuitry controlling human pluripotency. Nature Communications. 8(1):1149.
Hou PS, Chuang CY, Yeh CH, Chiang W, Liu HJ, Lin TN, Kuo HC*. (2017) Direct conversion of human fibroblasts into neural progenitors via the use of transcription factors highly enriched in human ESC-derived neural progenitors, Stem Cell Reports. 8(1):54-68.
Yu CY and Kuo HC*. (2016) The trans-spliced long noncoding RNA tsRMST impedes human ESC differentiation through WNT5A-mediated inhibition of the epithelial-to-mesenchymal transition, Stem Cells. 34(8):2052-62.
Chiu FL, Lin JT, Chuang CY, Chien T, Chen CM, Chen KH, Hsiao HY, Lin YS, Chern Y*, Kuo HC*. (2015) Elucidating the role of the A2A adenosine receptor in neurodegeneration using neurons derived from Huntington’s disease iPSCs”, Human Molecular Genetics. 24(21): 6066-6079.
Yu CY, Liu HJ, Kuo HC*, Chuang TJ*. (2014). Is an observed non-co-linear RNA product spliced in trans, in cis, or just in vitro? Nuclei Acids Research. 42(14):9410-23.
Lin YI, Chiu FL, Yeang CH, Chen HF, Chuang CY, Yang SY, Hou PS, Sintupisut N, Ho HN, Kuo HC*, Lin KI*. (2014) Suppression of the SOX2 neural effector gene by PRDM1 promotes human germ cell fate in embryonic stem cells. Stem Cell Reports. 2(2):189-204.
Wu CS, Yu CY, Chuang CY, Hsiao M, Kao CF, Kuo HC*, Chuang TJ*. (2014) Integrative transcriptome sequencing identifies trans-splicing events with important roles in human embryonic stem cell pluripotency. Genome Research. 24(1):25-36. (Highlighted by Nature Reviews Genetics)
Hou PS, Chuang CY, Kao CF, Chou SJ, Stone L, Ho HN, Chien Cl, Kuo HC*. (2013) LHX2 regulates the neural differentiation of human embryonic stem cells via transcriptional modulation of PAX6 and CER1. Nucleic Acids Research. 41(16):7753-7770.