91猫先生

研究方向及研究室特色

实验室研究主题：肠病毒 71 型及日本脑炎病毒之病毒复製和宿主之间的相互作用机制。

我们实验室主要从事高深的病毒与寄主互相作用的研究。目前实验室执行国科会计画有两大方向：

(一) 尝试将两种正股 RNA 病毒 (肠病毒 71 型 Enterovirus 71，EV71及 日本脑炎, Japanese Encephalitis Virus，JEV)，转型进入酵母菌中，测试其是否可以利用酵母菌為宿主进行复製；进一步利用这种最简单的真核生物，进行病毒与寄主蛋白的互动机制研究。这项研究策略是基於过去我在美国肯塔基大学病理学部门进行研究工作。我使用tombusvirus(一种感染於植物的 positive stranded RNA病毒)作為一个模型。加上以Yeast為宿主进行实验，成功地证明Glyceraldehyde-3-phosphate?dehydrogenas (GAPDH)，一种着名的代谢酵素，能透过它的选择性结合不同股?RNA?的能力提升RNA 病毒的复製。 这重要发现将领导病毒学家理解病毒能利用寄主细胞内原有的蛋白质,提供本身复製和演化的一项工具。 这也提供研究对抗病毒及病毒传染病作战的一个新的策略及线索。我的这项研究工作也发表於 Cell Host&Microbe , 这是全世界最好的研究病毒及寄主互相作用杂誌之一。

(二) 利用蛋白質體學方法，分析受到肠病毒 71 型及日本脑炎病毒感染後細胞之外分泌蛋白的組成，並且探討其可能影响病毒於體內複製，體外感染的機制。我的主要研究方向如下：

利用系统生物学的方式，包括基因组及蛋白质体的筛选方式，寻找可能参与/影响 RNA 病毒复製的宿主蛋白。进而研究这些蛋白对於病毒复製的角色与实际参与的功能。

分析及功能性阐述叁种 RNA 结合性宿主蛋白於 RNA 病毒复製过程中参与的角色。包括：Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), p68 DEAD-box RNA helicase homolog Dp2 以及蛋白转译延长因子 (EF-1 alpha)。

论文与着作

1.          Cheng CH, Peng YC, Lin SM, Yatsuda H,  Liu SH, Liu SJ,  Kuo CY, Wang RY* (corresponding author) (2022) Measurements of anti-SARS-CoV-2 antibody levels after vaccination using a SH-SAW biosensor. Biosensors. 12, 599. (SCI, impact factor: 5.743).

2.          Chen HH, Lin CJ, Anand A, Lin HJ, Lin HY, Mao JY, Wang PH, Tseng YJ, Tzou WS, Huang CC, Wang RY* (corresponding author) (2022) Development of antiviral carbon quantum dots that target the Japanese encephalitis virus envelope protein. J Biol Chem. 298(6): 101957. (SCI, impact factor: 5.486).

3.          Liu S, Dong Y, Wang Y, Hu P, Wang J, Wang RY* (corresponding author) (2021) Pristimerin exerts antitumor activity against MDA-MB-231 triple-negative breast cancer cells by reversing of epithelial-mesenchymal transition via downregulation of integrin b3. Biomedical J. 44: S84-S92. (SCI, impact factor: 7.892)

4.          Peng YC, Cheng CH, Yatsuda H, Liu SH, Liu SJ, Kogai T, Kuo CY, Wang RY*(corresponding author) (2021) A Novel Rapid Test to Detect Anti-SARS-CoV-2 N Protein IgG Based on Shear Horizontal Surface Acoustic Wave (SH-SAW). Diagnostics 11:1838 (SCI, impact factor: 3.992)

5.          Li YJ, Wu HH, Chen CH, Wang HH, Chiang YJ, Hsu HH, Pang ST, Wang RY, Tian YC (2021) High Incidence and Early Onset of Urinary Tract Cancers in Patients with BK Polyomavirus Associated Nephropathy. Viruses; 13: 476 (SCI, impact factor: 5.818)

6.          Liao T, Wang Xi, Donolato M, Cruz MM, Balmaseda A, Harris E, Wang RY*(corresponding author) (2020) Evaluation of ViroTrack Sero Zika IgG/IgM, a new rapid and quantitative Zika serological diagnostic assay. Diagnostics 10:372; doi:10.3390 (SCI, impact factor: 3.992)

7.          Xu P, Xu H, Cheng HS, Chan HH, Wang RY*(corresponding author) (2020) MicroRNA 876-5p modulates EV-A71 replication through downregulation of host antiviral factors. Virology Journal; 17:21   (SCI, impact factor: 5.922)

8.          Lai MC, Chen HH, Xu P, Wang RY*(corresponding author) (2020) Translational control of Enterovirus A71 gene expression. Journal of Biomedical Science; 27:22   (SCI, impact factor: 12.771)

9.          Lin CH, Chang L, Chu HW, Lin HJ, Chang PC, Wang RY*(corresponding author), Unnikrishnan B, Mao JY, Chen SY, Huang CC (2019) High amplification of the antiviral activity of curcumin through transformation into carbon quantum dots. Small; DOI: 10.1002/smll.201902641  (SCI, impact factor: 15.153)

10.      Li HY, Tsai MS, Huang CG, Wang RY, Chuang LP, Chen NH, Liu CH, Hsu CM, Cheng WN, Lee LA (2019) Alterations in Alzheimer’s disease-associated gene expression in severe obstructive sleep apnea patients. J. Clin. Med; 8: 1361; DOI: 10.3390/jcm8091361  (SCI, impact factor: 4.964)

11.      Chu HW, Lai CS, Ko JY, Harroun SG, Chuang CI, Wang RY*(corresponding author), Unnikrishnan B, Huang CC (2019) Nanoparticle-based LDI-MS immunoassay for the multiple diagnosis of viral infections. ACS Sensors; DOI: 10.1021/acssensors.9b00054  (SCI, impact factor: 9.618)

12.      Kuo RL, Chen CJ, Wang RY, Huang HI, Lin YH, Tam EH, Tu WJ, Wu SE, Shih SR (2019) Role of Enteroviral RNA-dependent RNA polymerase in regulation of MDA5-mediated beta interferon activation. J. Virology; 93 (10) e00132  (SCI, impact factor: 6.549)

13.      Chen YM, Ou BT, Chen CY, Chan HH, Chen CJ, Wang RY*(corresponding author) (2019) Staufen1 protein participates positively in the viral RNA replication of enterovirus 71. Viruses; 11 142; doi:10.3390/v11020142 (SCI, impact factor: 5.818)

14.      Min N, Vale DS, Wong AA, Tan WH, Chong CY, Chen CJ, Wang RY*(corresponding author), Chu JH* (2018) Circulating Salivary miRNA hsa-miR-221 as Clinically Validated Diagnostic Marker for Hand, Foot, and Mouth Disease in Pediatric Patients. EBioMedicine; 31: 299-306. (SCI, impact factor: 11.205) * Equally contributed authors

15.      Banerjee S, Aponte-Diaz D, Yeager C, Sharma SD, Ning G, Oh HS, Han Q, Umeda M, Hara Y, Wang RY, Cameron C (2018) Hijacking of multiple phospholipid biosynthetic pathways and induction of membrane biogenesis by a picornaviral 3CD protein. PLoS Pathog 14(5): e1007086 (SCI, impact factor: 7.464).

16.      Prabowo BA, Wang RY* (co-first author), Secario MK, Ou PT, Alom A, Liu JJ, Liu KC (2017) Rapid detection and quantification of Enterovirus 71 by a portable surface plasmon resonance biosensor. Biosensors & bioelectronics  DOI: 10.1016/j.bios.2017.01.043 (SCI, impact factor: 12.545) * Equally contributed authors

17.      Lin JJ, Wang RY, Chen CJ, Chiu CC, Liao MH, Wu YJ (2016) Cytotoxicity of 11-epi-Sinulariolide Acetate Isolated from Cultured Soft Corals on HA22T Cells through the Endoplasmic Reticulum Stress Pathway and Mitochondrial Dysfunction. Int. J. Mol. Sci; 17, 1787/doi:10.3390 (SCI, impact factor: 6.208).

18.      Wang RY, Li YJ, Lee WC, Wu HH, Lin CY, Lee CC, Chen YC, Hung CC, Yang CW, Tian YC (2016) The association between polyomavirus BK strains and BKV viruria in liver transplant recipients. Scientific Reports; 6:28491 | DOI: 10.1038 (SCI, impact factor: 4.996)

19.      Wang RY, Weng KF, Huang YC, Chen CJ (2016) Elevated expression of circulating miR876-5p is a specific response to severe EV71 infection. Scientific Reports; 6:24149 | DOI: 10.1038 (SCI, impact factor: 4.996)

20.      Wang RY, Wu YJ, Chen HS, Chen CJ (2016) A KDEL retrieval system for ER-Golgi transport of Japanese Encephalitis viral particles. Viruses; 8 (44); doi: 10.3390/v8020044 (SCI, impact factor: 5.818).

21.      Wang RY, Kuo RL, Yen SM, Chu CH, Wu JY, Huang YC, Chen CJ (2015). Proteome demonstration of alpha-1-acid glycoprotein and alpha-1-antichymotrypsin are candidate biomarkers for diagnosis of Enterovirus 71 infection. The Pediatric Infectious Disease Journal; 34:304-310 (SCI, impact factor: 3.806).

22.      Kuo RL, Lin YH, Wang RY, Hsu CW, Chiu YT, Huang HI, Kao LT, Yu JS, Shih SR, Wu CC. (2015). Proteomics Analysis of EV71-Infected Cells Reveals the Involvement of Host Protein NEDD4L in EV71Replication. J. Proteome Res; 14:1818-1830. (SCI, impact factor: 5.370)

23.      Weng KF, Hung CT, Hsieh PT, Li ML, Chen GW, Kung YA, Huang PN, Kuo RL, Chen LL, Lin JY, Wang RY, Chen SJ, Tang P, Horng JT, Huang HI, Wang, JR, Ojcius DM, Brewer G, Shih SR (2014) A cytoplasmic RNA virus generates functional viral small RNAs and regulates viral IRES activity in mammalian cells. Nucleic Acids Res. 42:12789-12805. (SCI, impact factor: 19.160)

24.      Su C-C, Yang Z-Y, Su J-H, Din Z-H, Wang RY*(corresponding author), Wu Y-J* (2014) 13-Acetoxysarcocrassolide induces apoptosis on human gastric carcinoma cells through mitochondria-related apoptotic pathways: p38/JNK activation and PI3K/AKT suppression. Mar. Drugs; 12: 5295-5315. (SCI, impact factor: 6.085). * Equally contributed authors

25.      Liu Y-C, Kuo R-L, Lin J-Y, Huang P-N, Huang Y, Liu H, Arnold J, Chen S-J, Wang RY, Cameron C, Shih S-R (2014) Cytoplasmic Viral RNA-Dependent RNA Polymerase Disrupts the Intracellular Splicing Machinery by Entering the Nucleus and Interfering with Prp8. PLOS Pathog 10(6): e1004199. doi:10.1371/journal.ppat.1004199. (SCI, impact factor: 7.464)

26.      Huang HI, Chen SK, Wang RY, Shen CR, Cheng YC (2013) Human Foreskin-derived Fibroblast-like Stromal Cells are able to Differentiate into Functional Hepatocyte-like Cells. Cell Biol International; 37(12): 1308-1319. (SCI, impact factor: 4.473)

27.      Wang RY, Kuo RL, Ma WC, Huang HI, Yu JS, Yen SM, Huang CR, Shih SR (2013) Heat Shock Protein-90-beta Facilitates Enterovirus 71 Viral Particles Assembly. Virology; 443: 236-247 (SCI, impact factor: 3.513).

28.      Kuo RL, Kao Li-Ting, Lin SJ, Wang RY, Shih SR (2013) MDA5 plays a crucial role in Enterovirus 71 RNA mediated IRF3 activation. PLoS ONE 8(5): e63431. doi:10.1371/journal.pone.0063431(SCI, impact factor: 3.752)

29.      Neoh CA*, Wang RY* (co-first author), Din ZH, Su JH, Chen YK, Tsai FJ, Weng SH, Wu YJ (2012) Induction of Apoptosis by Sinulariolide from Soft Coral through Mitochondrial-Related and p38MAPK Pathways on Human Bladder Carcinoma Cells. Mar. Drugs; 10: 2893-2911. (SCI, impact factor: 6.085) * Equally contributed authors

30.      Huang CR, Wang RY, Hsu SC, Lo SJ (2012) Lysine-71 in the Large Delta Antigen of Hepatitis Delta Virus Clade 3 Modulates its Localization and Secretion. Virus Res; 170: 75-84. (SCI, impact factor: 6.286)

31.      Liu CI*, Wang RY* (co-first author), Lin JJ, Su JH, Chiu CC, Chen JC, Chen JY, Wu YJ (2012) Proteomic Profiling of the 11-Dehydrosinulariolide-treated Oral Carcinoma Cells Ca9-22: effects on the cell apoptosis through Mitochondrial-related and ER stress pathway. J. Proteomics; 75:5578-5589. (SCI, impact factor: 3.855) * Equally contributed authors

32.      Wang RY, Kui Li. (2012) Host factors in the replication of positive-strand RNA viruses. Chang Gung Med J; 35: 111-124.

33.      Li YJ, Wu HH, Weng CH, Chen YC, Hung CC, Yang CW, Wang RY, Sakamoto N, Tian YC. (2012) Cyclophilin A and nuclear factor of activated T cells are essential in cyclosporin A-mediated suppression of polyomavirus BK replication. American J Transplantation; doi:10.1111/j.1600-6143.2012.04116.x. (SCI, impact factor: 9.369)

34.      Hung CY, Tsai MC, Wu YP, Wang RY*. (2011)  Identification of heat shock protein 90 beta in JEV-induced secretion proteins. Journal of General Virology; 92:2803-2809. (SCI, impact factor: 5.141) *Corresponding author

35.      Prasanth KR, Huang YW, Liou MR, Wang RY, Hu CC, Tsai CH, Meng M, Lin NS, Hsu YH. (2011)  Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) negatively regulates the replication of Bamboo mosaic virus and its associated satellite RNA. Journal of Virology; 85: 8829-8840. (SCI, impact factor: 6.549)

36.      Nagy PD, Wang RY, Pogany J, Hafren A, Makinen K.  (2011) Emerging picture of host chaperone and cyclophilin roles in RNA virus replication. Virology; 411:374-382. (SCI, impact factor: 3.513)

37.      Wang RY, Huang YR,  Chong KM, Hung CY, Ke ZL, Chang RY. (2011)  DnaJ homolog Hdj2 Facilitates Japanese Encephalitis Virus Replication. Virology J; 8:471. (SCI, impact factor: 5.922)

38.      Wu YP, Chang CM, Schuyler S, Hung CY, Tsai MC, Wang RY*. (2011) Japanese Encephalitis Virus Co-opts the ER-Stress Response Protein GRP78 for Viral Infectivity. Virology J; 8:128. (SCI, impact factor: 5.922) *Corresponding author.

39.      Wang RY, Stork J, Pogany J, Nagy PD. (2009) A temperature sensitive mutant of heat shock protein 70 reveals an essential role during the early steps of tombusvirus replication. Virology; 394:28-38. (SCI, impact factor: 3.513).

40.      Wang RY, Stork J, Nagy PD (2009). A key role for heat shock protein 70 in localization and insertion of the tombusvirus replication proteins to intracellular membranes. J. Virology; 83:3276-3287 (SCI, impact factor: 6.549)

41.      Wang RY, Nagy PD (2008). Tomato bushy stunt virus Co-Opts the RNA-Binding Function of a Host Metabolic Enzyme for Viral Genomic RNA Synthesis. Cell Host & Microbe; 3:178-187. (SCI, impact factor: 31.316).

42.      Wang RY, Shen CN, Tosh D, Lin MH, Shih C (2005). Hepatocyte-like cells transdifferentiated from pancreatic origin can support replication of hepatitis B virus. J. Virology;79:13116-13128. (SCI, impact factor: 6.549).

43.      Chua PK, Wang RY, Suk FM, Lin MH, Masuda T, and Shih C (2005). A Naturally Occurring Mutation (L77R) of Hepatitis B Virus Small S Envelope Gene Results in Low-Level Virion Secretion and Can be Suppressed by Another Natural Envelope Mutation (W74L). J. Virology;79:13483-13496. (SCI, impact factor: 6.549).

44.      Wang YL, Wu CY, Chang CT, Sung HY (2003). Invertase inhibitors from sweet potato (Ipomoea Batatas): purification and biochemical characterization. J. Agric. Food Chem;51:4804-4809. (SCI, impact factor: 5.895)

45.      Wang YL, Lee YH, Chen CC, Chang CT, Sung HY (1998). Purification and characterization of soluble acid invertase from yam tubers. J. Chinese Agric. Chem. Soc;36: 464-472. (SCI, impact factor: 1.753)