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Ching-Chi Chiu

Ching-Chi Chiu

ccchei

Highest Degree

Ph.D., Biochemistry and Molecular biology, Chang Gung University, Taiwan

Areas of Specialty

Neuroscience, Neurodegenerative diseases, Molecular Biology, induced pluripotent stem cell, Parkinson’s disease mutant gene knockin mice.

Office Phone

3708

Lab phone

5097

Research website:

Neurodegenerative Diseases Research Lab

E-mail

ccchei@mail.cgu.edu.tw

ccchei178@gmail.com

Lab & Research Interest

My laboratory explores four interrelated research studies: (1) application of precision medicine in Alzheimer's disease (AD) and Parkinson's disease (PD), (2) molecular diagnosis of AD and PD, (3) development of induced pluripotent stem cell (iPSC) and CRISPR/Cas9 gene editing for cell therapy, (4) mutant gene knockin/knockout mice and transgenic mice model of AD and PD.

We focus on two search studies: (1) the pathogenic mechanisms of Alzheimer's disease (AD) and Parkinson’s disease (PD) and (2) development of molecular biomarkers and therapeutic compounds for AD and PD. Upon identification of novel candidate genes from AD and PD patients, we generated primary cultured neurons, patient-derived induced pluripotent stem cells and CRISPR/Cas knockin mice and further study signaling pathways of these genes involved in neurodegeneration. We have earlier identified Ras-Related Protein 35 (RAB35) gene, involved in endocytic recycling, plays an important role in the abnormal α-synuclein protein aggregation in neurons. We further demonstrated that RAB35 promotes the secretion of α-synuclein to extracellular space and causes neuronal death. We generated induced pluripotent stem cells with PLA2G6 mutations and used for studying disease mechanisms. Role and mechanism of PLA2G6 that regulate neuronal is currently under investigation. Further studies are undertaken to examine other molecular mechanisms underlying PD-associated mutations and developed therapeutic strategies for PD.

Publication

I. Journal Papers

  1. 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 (Accepted) IF= 4.347, Ranking= 10/51; 19.60% (Geriatrics & Gerontology).
  2. 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 Dis. 2020 Nov 30;11(11):1018. doi: 10.1038/s41419-020-03228-9. IF= 6.304, Ranking= 40/195; 20.51% (Cell Biology).
  3. 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. Biochem Pharmacol. 2020 Mar 16:113919. doi:10.1016/j.bcp.2020.113919. IF= 4.960, Ranking= 26/270; 9.815% (Pharmacology & Pharmacy).
  4. 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= 2.439, Ranking= 112/204; 54.90% (Clinical Neurology).
  5. 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. Front Cell Neurosci. 2019 Sep 13; 13:399. IF=3.921, Ranking= 91/271; 33.40% (Neuroscience).
  6. 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= 4.489, Ranking= 27/156; 16.987% (Biotechnology & Applied microbiology).
  7. 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= 4.500, Ranking= 65/272; 23.897% (Neuroscience); 59/366; 16.12% (Neuroscience & Behavior).
  8. 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= 4.691, Ranking= 59/271; 21.587% (Neuroscience); 36/365 (Neuroscience & Behavior).
  9. 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. Ranking=62/321 (Oncology).
  10. 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. Ranking=62/321 (Oncology).
  11. 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. Ranking=62/321 (Oncology).
  12. 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= 2.630; 40.244% Ranking= 17/41 (Developmental Biology); 167/271, 61.439% (Neuroscience). 
  13. 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= 4.431, 43/271; 15.87% (Pharmacology & Pharmacy). 68/272; 25% (Neuroscience)
  14. 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= 4.691, Ranking=60/267, 21.59% (Neuroscience); 36/365 (Neuroscience & Behavior).
  15. 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= 3.935, Ranking= 8/41 (Developmental Biology); 89/271, 18.293% (Neuroscience).
  16. 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= 4.534, Ranking= 25/156; 15.705% (Biotechnology & Applied microbiology).
  17. 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= 2.740, Ranking= 27/71; 37.324% (Multidisciplinary Sciences).
  18. 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= 10.107, Ranking= 17/244; 6.762% (Oncology).
  19. 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. 2010 Sep 1;78(1):246-56. IF= 5.859, Ranking= 10/133; 7.143 (Radiology, nuclear medicine and imaging).
  20. 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= 4.534, Ranking= 25/156; 15.705% (Biotechnology & Applied microbiology).
  21. 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. 2010 Aug; 32(8):1028-39. IF= 2.538, Ranking= 9/42; 20.238% (Otorhinolaryngology).
  22. 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 Lett. 2009 Nov 1;284 (2):131-40. Epub 2009 May 19. IF= 7.360, Ranking= 30/244, 12.09 % (Oncology).
  23. 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= 5.615, Ranking= 50/244, 20.287% (Oncology).
  24. 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= 4.966, Ranking= 65/244, 26.434% (Oncology).
  25. 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= 7.971, Ranking= 26/244, 10.451% (Oncology).

II. Awards

  1. Outstanding Research Paper Award in Dec 2020, Chang Gung Memorial Hospital, Taiwan.
  2. Ta-You Wu Memorial Award in Sep 2020, Ministry of science and technology, Taiwan.
  3. Outstanding Research Paper Award in May 2020, Chang Gung Memorial Hospital, Taiwan.
  4. Outstanding Research Paper Award in June 2019, Chang Gung Memorial Hospital, Taiwan.
  5. 2018 Society for Neuroscience (SfN)-Merck Travel Award, USA.
  6. Outstanding Research Paper Award in May 2018, Chang Gung Memorial Hospital, Taiwan.
  7. Outstanding Research Paper Award in August 2016, Chang Gung Memorial Hospital, Taiwan.
  8. Second place prize at the 2rd Annual Contest of Master Thesis.
  9. College Student Research Creativity Award (2002 NSC)

III. Patents

A. Neurodegenerative disease

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, I695891, Patent date: 2020/6/11~ 2039/1/2

B. Cancer

  1. Specific Grp78 expression- inhibition RNAi sequence, medicine thereof and method thereof a method for head and neck cancer. US 7,825,100 B2. Patent date: 2010/11/2~ 2028/7/17
  2. Specific Grp78 expression- inhibition RNAi sequence, medicine thereof and method thereof specific Grp78-RNAi sequence. US 7,829,695 B2 Patent date: 2010/11/9/2010 ~ 2028/7/17