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醫學生物技術暨檢驗學系
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邱清旗 副教授 / Ching-Chi Chiu

职称： 副教授

现职： 长庚大学醫技系专任教师 / Ching-Chi Chiu

信箱： ccchei@mail.cgu.edu.tw ccchei178@gmail.com

电话： 3708

学歷： 长庚大学生物醫學研究所博士

专长领域： 神經科學、神经退化疾病、細胞分子生物學、誘導性多功能幹細胞、突變帕金森病基因嵌入小鼠、生物化學 、醫學生物技術

个人网页：

研究方向及研究室特色(Lab & Research Interest)

台湾帕金森病患者高达十万人，且帕金森病影响到的不只是个人，更会带来整个家庭经济、身心的重大压力及负担，本人以帕金森病為研究主轴，探讨神经退化病理机转，持续发展早期诊断与临床治疗而努力，也期许自己能真正帮助到全台湾十万个濒临疾病压力的家庭。由於基础及临床人力、物力资源的适切整合，本人得以从基础神经科学和临床病徵同时出发，相互验证。从临床检体、临床资料收集到实验室分子生物实验、动物模式的建立等，研究病理机转、开发小分子药物到临床诊断的应用，连结基础研究与临床诊断，兼具有经济价值和正面的社会影响。

实验室目前积极发展帕金森病(Parkinson’s disease)相关研究:

1.       帕金森病生物标记的开发

我们实验室利用蛋白质体与转录体学发现帕金森病患者血清检体有大量RAB35蛋白质与microRNA-204-5p的表现。我们研究发现藉由检测病患血清Rab35与α-蝉测苍耻肠濒别颈苍表現量，不僅提供臨床早期診斷帕金森病，更能精確區分在臨床症狀難以分別的帕金森病、多重系統退化症与進行性上核麻痺症。在帕金森病病患血清檢體和MPTP诱导帕金森病小鼠的中脑组织都具有大量表现的miR-204-5p，进而活化DYRK1A基因表现，进而引起磷酸化α-蝉测苍耻肠濒别颈苍和磷酸化Tau的增加，造成内质网压力和细胞自吞噬损坏(autophagy impairment)，导致多巴胺神经细胞死亡。发展生物标记能及早治疗帕金森病，提供病患未来更好的生活品质。

2.       突变帕金森病基因嵌入小鼠之应用

实验室建立世界首创早发性(early-onset)神经退化之帕金森病小鼠，并发现突变PLA2G6基因引起神经退化之机转。突变PLA2G6基因嵌入小鼠能提供作為开发神经保护药物的活体药物筛选平台。实验室同时也建立其他突变帕金森病基因嵌入小鼠，进行研究帕金森病分子机转研究。

3.       帕金森病患者诱导性多能干细胞(iPSCs)

我们实验室已从具有突变(D331Y/M358IfsX) PLA2G6帕金森病患者血液检体，建立诱导式多功能干细胞，并能分化為多巴胺神经细胞，除了探讨突变PLA2G6造成神经退化机转外，积极发展帕金森病的细胞治疗。实验室建立带有其他突变帕金森病基因的诱导性多能干细胞，进行神经退化机转研究。

4.       神經保護藥物与小分子開發

实验室发现研究发现，小分子化合物Alda-1能專一的与ALDH2蛋白结合并增加其活性，利用Alda-1活化多巴胺神经细胞内的ALDH2，不仅能减缓神经毒素诱导产生的自由基产生，也能维持粒线体膜电位和粒线体复合物活性，产生神经保护作用。在帕金森病小鼠模式也进一步证实，ALDH2的活化能减缓小鼠黑质区内自由基的产生，也抑制粒线体调控细胞凋亡路径的活化，产生神经保护作用。此研究结果提供ALDH2活化在帕金森病与其他神经退化疾病的治療應用和藥物開發。實驗室也積極開發其他神經保護藥物与小分子，期望未來能提供臨床病患治療。

5.       未来研究方向

除了积极研究帕金森病外，实验室也积极发展阿兹海默症(Alzheimer's disease)相关研究，利用臨床檢體、阿茲海默病患誘導性多能幹細胞与阿茲海默症相關基因嵌入小鼠進行神經退化之機轉与治療開發。

论文与着作(笔耻产濒颈肠补迟颈辞苍)

I.        论文

  1. von Maydell, D., Wright, S. E., Pao, P.-C., Staab, C., King, O., Spitaleri, A., Bonner, J. M., Liu, L., Yu, C.-J., Chiu, C.-C., Leible, D., Ní Scannail, A., Li, M., Boix, C. A., Mathys, H., Leclerc, G., Menchaca, G. S., Welch, G., Graziosi, A., Leary, N., Samaan, G., Kellis, M., & Tsai, L.-H. (2025 Sep 10). ABCA7 variants impact phosphatidylcholine and mitochondria in neurons. Nature, 638(8035), 66–74. DOI: 10.1038/s41586-025-09520-y(IF=48.5),Ranking=2/135,1.48% (MULTIDISCIPLINARY SCIENCES).

  2. Chiu CC, Weng YH, Yeh TH, Chen WS, Liu SY, Chiu TJ, Li AH, Wang HL. Absence of Rab39b-induced macroautophagy impairment increases neurotoxic α-蝉测苍耻肠濒别颈苍 and causes degeneration of substantia nigra dopaminergic neurons in mouse model of X-linked Parkinson's disease. Life Sci. 2025 Sep 15;377:123789. doi: 10.1016/j.lfs.2025.123789. (IF= 5.1), Ranking=44/159, 27.67 % (MEDICINE, RESEARCH & EXPERIMENTAL).

  3. Chiu CC, Chen YL, Weng YH, Liu SY, Li Allen HL, Yeh TH, Wang HL. Downregulation of protease cathepsin D and upregulation of pathologic α-蝉测苍耻肠濒别颈苍 mediate paucity of DNAJC6-induced degeneration of dopaminergic neurons. 2024 Jun 18;25(12):6711. doi: 10.3390/ijms25126711 (IF= 4.9), Ranking=66/313, 21.08 % (BIOCHEMISTRY & MOLECULAR BIOLOGY).

  4. Wang HL, Cheng YC, Yeh TH, Liu HF, Weng YH, Chen RS, Chen YC, Lu JC, Hwang TL, Wei KC, Liu YC, WangYT, Hsu CC, Chiu TJ, Chiu CC* (*Corresponding author). HCH6-1, an antagonist of formyl peptide receptor-1, exerts anti-neuroinflammatory and neuroprotective effects in cellular and animal models of Parkinson’s disease. Biochem Pharmacol. 2023 Mar 30;212:115524. (IF= 5.3), Ranking= 34/354, 9.6% (Pharmacology & Pharmacy).

  5. Chen YC, Chang SC, Lee YS, Ho WM, Huang YH, Wu YY, Chu YC, Wu KH, Wei LS, Wang HL*, Chiu CC* (*Corresponding author). TOMM40 genetic variants cause neuroinflammation in Alzheimer's disease. Int J Mol Sci. 2023 Feb 17;24(4):4085. doi: 10.3390/ijms24044085. IF= 4.9, Ranking= 66/313, 21.08 %, (Biochemistry & Molecular Biology).

  6. Chiu CC, Weng YH, Yeh TH, Lu JC, Chen WS, Li AHR, Chen YL, Wei KC, Wang HL. Deficiency of RAB39B activates ER stress-induced pro-apoptotic pathway and causes mitochondrial dysfunction and oxidative stress in dopaminergic neurons by impairing autophagy and upregulating α-蝉测苍耻肠濒别颈苍. Molecular Neurobiology 2023 May;60(5):2706-2728. doi: 10.1007/s12035-023-03238-6. Epub 2023 Jan 30. IF= 4.6, Ranking=66/310, 21.29% (Neurosciences).

  7. Chiu CC, Lee HT and Kuo YM. Editorial: Insights in Neuroinflammation and Neuropathy. Front Aging Neurosci. 2022 Nov 10;14:1060271, IF= 4.1, Ranking= 80/310, 25.80% (Neurosciences). 

  8. Lee CH; Hunt D; Roth JD; Chiu CC; Suhar RA; LeSavage BL; Seymour AJ; Lindsay C; Krajina B; Chen YT; Chang KH; Hsieh IC, Heilshorn S. Tuning pro-survival effects of human induced pluripotent stem cell-derived exosomes using elastin-like polypeptides. Biomaterials. 2022 Dec;291:121864. doi: 10.1016/j.biomaterials.2022.121864. Epub 2022 Oct 26. IF=12.8, Ranking= 4/122, 3.28% (Engineering, Biomedical).

  9. Tsao SP, Nurrahma BA, Kumar R, Wu CH, Yeh TH, Chiu CC, Lee YP, Liao YC, Huang CH, Yeh YT, Huang HY. Probiotic supplementation enhances antioxidant capacity and is associated with gut microbiota composition alterations in rats with 6-OHDA-induced Parkinson’s Disease. Antioxidants. 2021;10(11):1823. doi: 10.3390/antiox10111823. IF= 6.0, Ranking= 50/313; 15.97% (BIOCHEMISTRY & MOLECULAR BIOLOGY).

  10. Yeh TH, Liu HF, Chiu CC, Cheng ML, Huang GJ, Huang YC, Liu YC, Huang YZ, Lu CS, Chen YC, Chen HY, Cheng YC. PLA2G6 mutations cause motor dysfunction phenotypes of young-onset dystonia–parkinsonism type 14 and can be relieved by DHA treatment in animal models. Exp Neurol. 2021 Dec;346:113863. doi: 10.1016/j.expneurol.2021.113863. Epub 2021 Sep 11. IF= 4.6, Ranking= 66/310; 21.29% (Neuroscience).

  11. Wang HL, Yeh TH, Huang YZ, Weng YH, Chen RS, Wei KC, Lu CS, Liu YC, Shen YM, Chen CL, Chen YJ, Hsu CC, Chiu CH, Lin YW, Chiu CC* (*Corresponding author). Functional variant rs17525453 within RAB35 gene promoter is possibly associated with increased risk of Parkinson's disease in Taiwanese population. Neurobiology of Aging. 2021 Nov; 107:189-196. doi: 10.1016/j.neurobiolaging.2021.06.011. IF= 3.7, Ranking= 26/74, 35.14% (Geriatrics & Gerontology); 98/310, 31.61% (Neurosciences).

  12. Chiu CC, Weng YH, Huang YZ, Chen RS, Liu YC, Yeh TH, Lu CS, Lin YW, Chen YJ, Hsu CC, Chiu CH, Wang YT, Chen WS, Liu SY, Wang HL. (D620N) VPS35 causes the impairment of Wnt/β-catenin signaling cascade and mitochondrial dysfunction in a PARK17 knockin mouse model. Cell Death & Disease. 2020 Nov 30;11(11):1018. doi: 10.1038/s41419-020-03228-9. IF= 8.1, Ranking= 33/205; 16.09% (Cell Biology).

  13. Liu YC, Wang HL, Huang YZ, Weng YH, Chen RS, Tsai WC, Yeh TH, Lu CS, Chen YL, Lin YW, Chen YJ, Hsu CC, Chiu CH, Chiu CC* (*Corresponding author). Alda-1, an activator of ALDH2, ameliorates Achilles tendinopathy in cellular and mouse models. Biochemical Pharmacology. 2020 Mar 16:113919. doi:10.1016/j.bcp.2020.113919. (IF= 5.3), Ranking= 34/354, 9.6% (Pharmacology & Pharmacy).

  14. Wang HL, Lu CS, Yeh TH, Shen YM, Weng YH, Huang YZ, Chen RS, Liu YC, Cheng YC, Chang HC, Chen YL, Chen YJ, Lin YW, Hsu CC, Chiu CC* (*Corresponding author). Combined assessment of serum alpha-synuclein and Rab35 is a better biomarker for Parkinson's disease. J Clin Neurol. 2019 Oct;15(4):488-495. IF= 2.9, Ranking= 99/277; 35.74% (Clinical Neurology).

  15. Chiu CC, Yeh TH, Chen RS, Chen HC, Huang YZ, Weng YH, Cheng YC, Liu YC, Cheng AJ, Lu YC, Chen YJ, Lin YW, Hsu CC, Chen YL, Lu CS, Wang HL. Upregulated expression of microRNA-204-5p leads to the death of dopaminergic cells by targeting DYRK1A-mediated apoptotic signaling cascade. Frontiers in Cellular Neuroscience. 2019 Sep 13; 13:399. IF= 4.2, Ranking= 78/310; 25.16% (Neuroscience).

  16. Chiu CC, Wang HL, Weng YH, Chen RS, Chen CM, Yeh TH, Lu CS, Chen YJ, Liu YC, Huang YZ and Chang KH. Generation of induced pluripotent stem cells from a young-onset Parkinson's disease patient carrying the compound heterozygous PLA2G6 p.D331Y/p.M358IfsX mutations. Stem Cell Res. 2019 Oct; 40:101552. IF= 0.8, Ranking= 166/174; 95.4% (Biotechnology & Applied microbiology).

  17. Chiu CC, Lu CS, Weng YH, Chen YL, Huang YZ, Chen RS, Cheng YC, Huang YC, Liu YC, Lai SC, Lin KJ, Lin YW, Chen YJ, Chen CL, Yeh TH, Wang HL. PARK14 (D331Y) PLA2G6 causes early-onset degeneration of substantia nigra dopaminergic neurons by inducing mitochondrial dysfunction, ER stress, mitophagy impairment and transcriptional dysregulation in a knockin mouse model. Mol Neurobiol. 2019 Jun;56(6):3835-3853. IF= 4.6, Ranking=66/310, 21.29% (Neurosciences).

  18. Yeh TH, Liu HF, Li YW, Lu CS, Shih HY, Chiu CC, Lin SJ, Huang YC, Cheng YC. C9orf72 is essential for neurodevelopment and motility mediated by Cyclin G1. Exp Neurol. 2018 Mar 6;304: 114-124. IF= 4.6, Ranking= 66/310; 21.29% (Neuroscience).

  19. Chiu CC, Yeh TH, Lu CS, Huang YC, Cheng YC, Huang YZ, Weng YH, Liu YC, Lai SC, Chen YL, Chen YJ, Chen CL, Chen HY, Lin YW, Wang HL. PARK14 PLA2G6 mutants are defective in preventing rotenone-induced mitochondrial dysfunction, ROS generation and activation of mitochondrial apoptotic pathway. Oncotarget. 2017 Sep 15;8(45):79046-79060. IF= 5.168, Ranking= 44/217, 20.28% (Oncology).

  20. Huang YC, Lin SJ, Shih HY, Chou CH, Chu HH, Chiu CC, Yuh CH, Yeh TH, Cheng YC. Epigenetic regulation of NOTCH1 and NOTCH3 by KMT2A inhibits glioma proliferation. Oncotarget. 2017 Jun 27;8(38):63110-63120. IF= 5.168, Ranking= 44/217, 20.28% (Oncology).

  21. Chiu CC, Yeh TH, Lai SC, Huang YC, Chen YJ, Chen CL, Wang HL, Lu CS. Increased Rab35 expression is a potential biomarker and implicated in the pathogenesis of Parkinson's disease. Oncotarget. 2016 Aug 23;7(34):54215-54227. IF= 5.168, Ranking= 44/217, 20.28% (Oncology). 

  22. Cheng YC, Huang YC, Yeh TH, Shih HY, Lin CY, Lin SJ, Chiu CC, Huang CW, Jiang YJ. Deltex1 is inhibited by the Notch-Hairy/E(Spl) signaling pathway and induces neuronal and glial differentiation. Neural Dev. 2015 Dec 30;10:28. IF= 4.0; Ranking=7/39, 17.95% (Developmental Biology); 86/310, 27.74% (Neuroscience).  

  23. Chou AH, Chen YL, Chiu CC, Yuan SJ, Weng YH, Yeh TH, Lin YL, Fang JM, Wang HL. T1-11 and JMF1907 ameliorate polyglutamine-expanded ataxin-3-induced neurodegeneration, transcriptional dysregulation and ataxic symptom in the SCA3 transgenic mouse. Neuropharmacology. 2015 Aug 6;99:308-317. IF=4.6, Ranking= 57/354; 16.10% (Pharmacology & Pharmacy); 66/310; 21.29% (Neuroscience)

  24. Chiu CC, Yeh TH, Lai SC, Wu-Chou YH, Chen CH, Mochly-Rosen D, Huang YC, Chen YJ, Chen CL, Chang YM, Wang HL, Lu CS. Neuroprotective effects of aldehyde dehydrogenase 2 activation in rotenone-induced cellular and animal models of parkinsonism. Exp Neurol. 2015 Jan; 263:244-53. IF= 4.6, Ranking= 66/310; 21.29% (Neuroscience).

  25. Huang YC, Shih HY, Lin SJ, Chiu CC, Ma TL, Yeh TH, Cheng YC. The epigenetic factor Kmt2a/Mll1 regulates neural progenitor proliferation and neuronal and glial differentiation. Dev Neurobiol. 2015 May;75(5):452-62. IF= 2.7, Ranking= 13/39, 33.33% (Developmental Biology); 158/310, 50.97% (Neuroscience).

  26. Chiu CC, Lee LY, Li YC, Chen YJ, Lu YC, Li YL, Wang HM, Chang JT, Cheng AJ. Grp78 as a therapeutic target for refractory head-neck cancer with CD24(-)CD44(+) stemness phenotype. Cancer Gene Ther. 2013 Nov;20(11):606-15. IF= 4.8, Ranking= 27/174, 15.52 % (Biotechnology & Applied microbiology); 29/191, 15.18% (Genetics & Heredity), 45/189; 23.8% (Medicine, Research & Experimental); 70/322, 21.74% (Oncology).

  27. Chen YJ, Lee LY, Chao YK, Chang JT, Lu YC, Li HF, Chiu CC, Li YC, Li YL, Chiou JF, Cheng AJ. DSG3 facilitates cancer cell growth and invasion through the DSG3-plakoglobin-TCF/LEF-Myc/cyclin D1/MMP signaling pathway. PLoS One. 2013 May 30;8(5): e64088. IF= 2.9, Ranking= 31/134; 23.13% (Multidisciplinary Sciences).

  28. Chiu CC, Lin CY, Lee LY, Chen YJ, Lu YC, Wang HM, Liao CT, Chang JT, Cheng AJ. Molecular chaperones as a common set of proteins that regulate the invasion phenotype of head and neck cancer. Clin Cancer Res. 2011 Jul 15; 17(14):4629-41. IF= 10.0, Ranking= 27/322; 8.39% (Oncology).

  29. Lin TY, Chang JT, Wang HM, Chan SH, Chiu CC, Lin CY, Fan KH, Liao CT, Chen IH, Liu TZ, Li HF, Cheng AJ. Proteomics of the radioresistant phenotype in head-and-neck cancer: Gp96 as a novel prediction marker and sensitizing target for radiotherapy. Int J Radiat Oncol Biol Phys. (EISSN 1879-355X) (ISSN 0360-3016) 2010 Sep 1;78(1):246-56. IF= 6.4, Ranking= 46/322, 14.29% (Oncology)14/204, 6.86% (Radiology, nuclear medicine and imaging).

  30. Chang JT, Kuo TF, Chen YJ, Chiu CC, Lu YC, Li HF, Shen CR, Cheng AJ. Highly potent and specific siRNAs against E6 or E7 genes of HPV16- or HPV18-infected cervical cancers. Cancer Gene Ther. 2010 Dec;17(12):827-36. IF= 4.8, Ranking= 27/174, 15.52 % (Biotechnology & Applied microbiology); 29/191, 15.18% (Genetics & Heredity), 45/189; 23.81% (Medicine, Research & Experimental); 70/322, 21.74% (Oncology).

  31. Lin CY, Chen WH, Liao CT, Chen IH, Chiu CC, Wang HM, Yen TC, Lee LY, Chang JT, Cheng AJ. Positive association of glucose-regulated protein 78 during oral cancer progression and the prognostic value in oral precancerous lesions. Head Neck (EISSN 1097-0347) (ISSN 1043-3074). 2010 Aug; 32(8):1028-39. IF= 2.3, Ranking= 14/65; 21.54% (Otorhinolaryngology); 79/290, 27.24% (Surgery).

  32. Kang CJ, Chen YJ, Liao CT, Wang HM, Chang JT, Lin CY, Lee LY, Wang TH, Yen TC, Shen CR, Chen IH, Chiu CC, Cheng AJ. Transcriptome profiling and network pathway analysis of genes associated with invasive phenotype in oral cancer. Cancer Letters. 2009 Nov 1;284 (2):131-40. Epub 2009 May 19. IF= 9.1, Ranking= 33/322, 10.25% (Oncology).

  33. Chiu CC, Lin CY, Lee LY, Chen YJ, Kuo TF, Chang JT, Liao CT, Wang HM, Yen TC, Shen CR, Liao SK, Cheng AJ. Glucose-regulated protein 78 regulates multiple malignant phenotypes in head and neck cancer and may serve as a molecular target of therapeutic intervention. Mol Cancer Ther. 2008 Sep; 7(9):2788-97. IF= 5.3, Ranking= 61/322, 18.94% (Oncology).

  34. Chen YJ, Chang JT, Liao CT, Wang HM, Yen TC, Chiu CC, Lu YC, Li HF, Cheng AJ. Head and neck cancer in the betel quid chewing area: recent advances in molecular carcinogenesis. Cancer Sci. 2008 Aug;99(8):1507-14. IF= 4.5, Ranking= 78/322, 24.22% (Oncology).

  35. Chen YJ, Chang JT, Lee L, Wang HM, Liao CT, Chiu CC, Chen PJ, Cheng AJ. DSG3 is overexpressed in head neck cancer and is a potential molecular target for inhibition of oncogenesis. Oncogene. 2007 Jan 18;26(3):467-76. IF= 6.9, Ranking= 36/313, 11.50% (Biochemistry & Molecular biology); 40/205, 19.51% (Cell biology); 16/191, 8.3% (Genetics & Heredity); 42/322, 13.04% (Oncology).


II.   
获奖情形

  1. 112年度醫學院优良教师-年輕學者研究獎

  2. 2023国科会乙种研究奖励补助

  3. 2022国科会乙种研究奖励补助

  4. 2021 Taiwan Innotech Expo Invention Award- Bronze Medal Award (2021台灣創新技術博覽會發明競賽銅牌獎)

  5. Outstanding Research Paper Award in Dec 2020, Chang Gung Memorial Hospital, Taiwan (長庚醫院優秀论文).

  6. Ta-You Wu Memorial Award in Sep 2020, MOST (吴大猷先生纪念奖)

  7. Outstanding Research Paper Award in May 2020, Chang Gung Memorial Hospital, Taiwan (長庚醫院優秀论文).

  8. Outstanding Research Paper Award in June 2019, Chang Gung Memorial Hospital, Taiwan (長庚醫院優秀论文).

  9. 2018 Society for Neuroscience (SfN)-Merck Travel Award

  10. Outstanding Research Paper Award in May 2018, Chang Gung Memorial Hospital, Taiwan (長庚醫院優秀论文).

  11. Outstanding Research Paper Award in August 2016, Chang Gung Memorial Hospital, Taiwan (長庚醫院優秀论文).

  12. Second place prize at the 2rd Annual Contest of Master Thesis.

  13. College Student Research Creativity Award (2002 NSC)


III.     专利

A.      神经退化疾病(帕金森病)相關专利

發明专利名稱: 早发型帕金森病(D331Y) PLA2G6突變基因嵌入模式与藥物篩選平台和方法，发明人:邱清旗、王鴻利、葉篤學，中華民國专利字號: I695891，专利權期間: 2020/6/11~ 2039/1/2

B.       癌症相關专利

1.       發明专利名稱:专一性抑制葡萄糖调节蛋白78 (Grp78)表现之RNA干扰(RNAi)序列、抑制药剂及抑制方法，发明人:鄭恩加、張東杰、邱清旗，中華民國专利字號:I-371285、专利權期間: 2012年9月1日~ 2028年1月10日

2.       發明专利名稱:Specific Grp78 expression- inhibition RNAi sequence, medicine thereof and method thereof _ a method for head and neck cancer，发明人:鄭恩加、張東杰、邱清旗，美國专利字號:US 7,825,100 B2，专利權期間:2010/11/2 ~ 2028/7/17

3.       發明专利名稱:Specific Grp78 expression- inhibition RNAi sequence, medicine thereof and method thereof _ specific Grp78-RNAi sequence.，发明人:鄭恩加、張東杰、邱清旗，美國专利字號:US 7,829,695 B2，专利權期間:2010/11/9/2010 ~ 2028/7/17