The goals of Dr. Wang’s research are focused on the interaction of host factors and RNA viruses. Their first project is in the field of developing of yeast as a model host and powerful in vitro assay with purified replicase complexes, together with reverse genetic approaches that make Enterovirus 71 (EV71), Japanese Encephalitis Virus, capable of replicating in yeast, as to study fundamental aspects of viral RNA replication. The second project, Dr. Wang’s laboratory will use proteomic approaches to analyze infection of two cell lineages, RD cells and SF268 cells, with EV71, focusing on the secreted proteins. First, they will identify several secreted proteins which are found only in the EV71-infected cells by the combination using of one dimension electrophoresis and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Second, they will perform 2D-electrophoresis followed by MALDI-TOF/TOF in order to validate those proteins. Once they identify the host proteins which were presented in the secreted proteins of EV71-infected cells, they will discuss the results obtained taking into account the proteins previously described in the secretome of virus-infected mammalian cells, proteins present in human plasma and proteins of interest for EV71 pathogenesis. Altogether these data will provide clues for the progress in the understanding of the role of host secretion in disease progression.The specific aims are:
- Identification of numerous host factors affecting/involving viral replication by using a systems biology approach, including genome-wide screens and proteomics approaches.
- Dissecting the roles of three RNA-binding host proteins: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the p68 DEAD-box RNA helicase homolog Dpb2 and translation elongation factor EF-1alpha (Tef1/2p), all of which bind to TBSV RNA and also known to interact with Hepatitis C virus, West Nile virus, dengue 4 virus and hepatitis A virus RNAs, suggesting that host factors might play similar roles in replication of these viruses.
- Roles of Vacuolar Protein sorting proteins in RNA virus replication.
- 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. Biosens. Bioelectron. DOI: 10.1016/j.bios.2017.01.043 (SCI, impact:7.476) * Equally contributed authors
- 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: 3.257).
- 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: 5.228)
- 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: 5.228).
- 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: 3.042).
- 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: 2.587).
- 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: 4.173)
- 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: 9.202)
- 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: 3.345). * Equally contributed authors
- 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: 7.003)
- 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: 1.663)
- 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: 3.200).
- 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: 3.057)