感染症與疫苗研究所
連絡電話：(+886) 037-246166 ext.37777
傳真電話：(+886) 037-586457
電子郵箱：
chunhong@nhri.org.tw
學歷
| 1995/09 – 2001/09 |
Ph.D., National Yang-Ming University, Taipei,Taiwan |
| 1993/09 – 1995/09 |
M.S., National Taiwan University, Taipei,Taiwan |
| 1986/09 – 1991/07 |
B.S., National Taiwan University, Taipei,Taiwan |
經歷
| 2008/09 – 2009/01 |
Senior Research Fellow, Biology, Caltech, Pasadena CA |
| 2003/01 – 2008/09 |
Postdoctoral fellow, Biology, Caltech, Pasadena CA |
| 2001/09 – 2003/01 |
Postdoctoral fellow, Inst. Mol. Bio., Academia Sinica, Taipei,Taiwan |
Expertise
MicroRNA, Cell death, Innate Immunity, Gene Driver
Research Interests
1 microRNAs and diseases:
The importance of microRNAs in the regulation of diverse biological processes is reflected in the growing list of human diseases. It is becoming evident that these RNA regulations play particularly important roles in neurologic disease, cancers and immune response.
We have carried out several screens for cell death regulators in the fly and have identified a number of new molecules. Among these are multiple microRNAs, small noncoding RNAs that function by inhibiting translation of target transcripts. We are interested in determining when and where these molecules regulate death and innate immunity as well as the nature of their targets. We are also designing microRNAs that target known cell death regulators as a way of probing the function of these proteins in specific contexts.
2 Establish gene driver systems in transgenic Drosophila and Mosquitoes
Dengue virus is the most important arbovirus affecting human. The mosquito Aedes aegypti transmits. Dengue virus (DENV) to human, resulting estimated 50 million infections annually is an urgent need to consider how to minimize the public health impacts.
Developing a genetic control strategy to reduce vector competence and transmission of dengue virus is one of potential strategies. Using RNAi to reduce virus replication can create an anti-viral effecter gene for the virus control. These effecter genes can be coupled into a gene drive system to spread into population. To achieve the anti-viral effecter gene, we generated a microRNA based RNAi system to knock-down DENV genomes in Aedes aegypti. The synthetic single and polycistronic microRNAs in the system will inhibit one or multiple different DENV genomes. We have investigated a maternal gene drive system called Medea in Drosophila (Chen et al 2007). Medea is a synthetic selfish element; it may spread the cargo gene (or an anti-viral gene in this case) throughout population in a few generations. The element also uses microRNAs to silence a maternally expressed gene which is essential for embryogenesis, and couples with early zygotic expression of the rescuing transgene. We propose all of the components required for building a Medea of mosquito Aedes aegypti will be identified. The final goal is to establish a transgenic mosquito platform that takes advantage of the micro RNA-based RNA interference and the gene drive system to further create the dengue virus control strategy by these genetic engineered insects.
Publication:
2020
Long KC, Alphey L, Annas GJ, Bloss CS, Campbell KJ, Champer J, Chen CH,
Choudhary A, Church GM, Collins JP, Cooper KL, Delborne JA, Edwards OR, Emerson
CI, Esvelt K, Evans SW, Friedman RM, Gantz VM, Gould F, Hartley S, Heitman E,
Hemingway J, Kanuka H, Kuzma J, Lavery JV, Lee Y, Lorenzen M, Lunshof JE,
Marshall JM, Messer PW, Montell C, Oye KA, Palmer MJ, Papathanos PA, Paradkar
PN, Piaggio AJ, Rasgon JL, Rašić G, Rudenko L, Saah JR, Scott MJ, Sutton JT,
Vorsino AE, Akbari OS. Core commitments for field trials of gene drive
organisms.
Science. 2020 Dec 18;370(6523):1417-1419. doi:
10.1126/science.abd1908. PMID: 33335055.
Lataillade LG, Vazeille M, Obadia T, Madec Y, Mousson L, Kamgang B, Chen CH,
Failloux AB, Yen PS. Risk of yellow fever virus transmission in the Asia-Pacific
region.
Nat Commun. 2020 Nov 16;11(1):5801. doi: 10.1038/s41467-020-19625-9.
PMID: 33199712; PMCID: PMC7669885.
Liu LT, Chen CH, Tsai CY, Lin PC, Hsu MC, Huang BY, Wang YH, Tsai JJ.
Evaluation of rapid diagnostic tests to detect dengue virus infections in
Taiwan.
PLoS One. 2020 Sep 29;15(9):e0239710. doi: 10.1371/journal.pone.0239710.
PMID: 32991592; PMCID: PMC7524001.
Cheng L, Liu WL, Li HH, Su MP, Wu SC, Chen HW, Pan CY, Tsai JJ, Chen CH.
Releasing Intracellular NS1 from Mosquito Cells for the Detection of Dengue
Virus-Infected Mosquitoes.
Viruses. 2020 Sep 29;12(10):1105. doi:
10.3390/v12101105. PMID: 33003584; PMCID: PMC759988
Tsai HY, Wu SC, Li JC, Chen YM, Chan CC, Chen CH. Loss of the
<i>Drosophila</i> branched-chain α-ketoacid dehydrogenase complex results in
neuronal dysfunction.
Dis Model Mech. 2020 Aug 27;13(8):dmm044750. doi:
10.1242/dmm.044750. PMID: 32680850; PMCID: PMC7473638.
Li HH, Cai Y, Li JC, Su MP, Liu WL, Cheng L, Chou SJ, Yu GY, Wang HD, Chen
- C-Type Lectins Link Immunological and Reproductive Processes in Aedes
aegypti.
iScience. 2020 Aug 21;23(9):101486. doi: 10.1016/j.isci.2020.101486.
Epub ahead of print. PMID: 32891883; PMCID: PMC7481239.
Cheng YC, Lee FJ, Hsu YT, Slud EV, Hsiung CA, Chen CH, Liao CL, Wen TH,
Chang CW, Chang JH, Wu HY, Chang TP, Lin PS, Ho HP, Hung WF, Chou JD, Tsou HH.
Real-time dengue forecast for outbreak alerts in Southern Taiwan.
PLoS Negl Trop
Dis. 2020 Jul 27;14(7):e0008434. doi: 10.1371/journal.pntd.0008434. PMID:
32716983; PMCID: PMC7384612.
Liu W, Duan X, Xu L, Shang W, Zhao J, Wang L, Li JC, Chen CH, Liu JP, Tong C.
Chchd2 regulates mitochondrial morphology by modulating the levels of Opa1.
Cell
Death Differ. 2020 Jun;27(6):2014-2029. doi: 10.1038/s41418-019-0482-7. Epub
2020 Jan 6. PMID: 31907391; PMCID: PMC7244760.
Chen PL, Huang KT, Cheng CY, Li JC, Chan HY, Lin TY, Su MP, Yang WY, Chang
HC, Wang HD, Chen CH. Vesicular transport mediates the uptake of cytoplasmic
proteins into mitochondria in Drosophila melanogaster.
Nat Commun. 2020 May
22;11(1):2592. doi: 10.1038/s41467-020-16335-0. PMID: 32444642; PMCID:
PMC7244744.
Pan CY, Liu WL, Su MP, Chang TP, Ho HP, Shu PY, Huang JJ, Lin LJ, Chen CH.
Epidemiological analysis of the Kaohsiung city strategy for dengue fever
quarantine and epidemic prevention.
BMC Infect Dis. 2020 May 15;20(1):347. doi:
10.1186/s12879-020-4942-y. PMID: 32414340; PMCID: PMC7226716.
Buchman A, Gamez S, Li M, Antoshechkin I, Li HH, Wang HW, Chen CH, Klein MJ,
Duchemin JB, Crowe JE Jr, Paradkar PN, Akbari OS. Correction: Broad dengue
neutralization in mosquitoes expressing an engineered antibody.
PLoS Pathog.
2020 Apr 29;16(4):e1008545. doi: 10.1371/journal.ppat.1008545. Erratum for: PLoS
Pathog. 2020 Jan 16;16(1):e1008103. PMID: 32348355; PMCID: PMC7190102.
Lai YW, Chu SY, Li JC, Chen PL, Chen CH, Yu HH. Visualization of Endogenous
Type I TGF-β Receptor Baboon in the Drosophila Brain.
Sci Rep. 2020 Mar
20;10(1):5132. doi: 10.1038/s41598-020-61950-y. PMID: 32198477; PMCID:
PMC7083856.
Sun P, Nie K, Zhu Y, Liu Y, Wu P, Liu Z, Du S, Fan H, Chen CH, Zhang R, Wang
P, Cheng G. A mosquito salivary protein promotes flavivirus transmission by
activation of autophagy.
Nat Commun. 2020 Jan 14;11(1):260. doi:
10.1038/s41467-019-14115-z. PMID: 31937766; PMCID: PMC6959235.
2019
Tsai YW, Sung HH, Li JC, Yeh CY, Chen PY, Cheng YJ, Chen CH, Tsai YC, Chien
- Glia-derived exosomal miR-274 targets Sprouty in trachea and synaptic
boutons to modulate growth and responses to hypoxia.
Proc Natl Acad Sci U S A.
2019 Dec 3;116(49):24651-24661. doi: 10.1073/pnas.1902537116. Epub 2019 Oct 30.
PMID: 31666321; PMCID: PMC6900535.
Du S, Liu Y, Liu J, Zhao J, Champagne C, Tong L, Zhang R, Zhang F, Qin CF, Ma
P, Chen CH, Liang G, Liu Q, Shi PY, Cazelles B, Wang P, Tian H, Cheng G. Aedes
mosquitoes acquire and transmit Zika virus by breeding in contaminated aquatic
environments.
Nat Commun. 2019 Mar 22;10(1):1324. doi:
10.1038/s41467-019-09256-0. PMID: 30902991; PMCID: PMC6430813.
Tsai JJ, Liu WL, Lin PC, Huang BY, Tsai CY, Lee PA, Tsai YL, Chou PH, Chung
S, Liu LT, Chen CH. A fully automated sample-to-answer PCR system for easy and
sensitive detection of dengue virus in human serum and mosquitos.
PLoS One. 2019
Jul 10;14(7):e0218139. doi: 10.1371/journal.pone.0218139. PMID: 31291289; PMCID:
PMC6619671
Yen PS, Chen CH, Sreenu V, Kohl A, Failloux AB. Assessing the Potential
Interactions between Cellular miRNA and Arboviral Genomic RNA in the Yellow
Fever Mosquito, <i>Aedes aegypti</i>.
Viruses. 2019 Jun 10;11(6):540. doi:
10.3390/v11060540. PMID: 31185697; PMCID: PMC6631873.
Tsai JJ, Liu WL, Lin PC, Huang BY, Tsai CY, Chou PH, Lee FC, Ping CF, Lee
PA, Liu LT, Chen CH. An RT-PCR panel for rapid serotyping of dengue virus
serotypes 1 to 4 in human serum and mosquito on a field-deployable PCR system.
PLoS One. 2019 Mar 25;14(3):e0214328. doi: 10.1371/journal.pone.0214328. PMID:
30908535; PMCID: PMC6433249.
Buchman A, Gamez S, Li M, Antoshechkin I, Li HH, Wang HW, Chen CH, Klein MJ,
Duchemin JB, Paradkar PN, Akbari OS. Engineered resistance to Zika virus in
transgenic <i>Aedes aegypti</i> expressing a polycistronic cluster of synthetic
small RNAs.
Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3656-3661. doi:
10.1073/pnas.1810771116. Epub 2019 Feb 5. PMID: 30723148; PMCID: PMC6397566.
Yuan HY, Wen TH, Kung YH, Tsou HH, Chen CH, Chen LW, Lin PS. Prediction of
annual dengue incidence by hydro-climatic extremes for southern Taiwan.
Int J
Biometeorol. 2019 Feb;63(2):259-268. doi: 10.1007/s00484-018-01659-w. Epub 2019 Jan 24. PMID: 30680621.
2018
Sun X, Duan Y, Qin C, Li JC, Duan G, Deng X, Ni J, Cao X, Xiang K, Tian K,
Chen CH, Li A, Fang Y. Distinct multilevel misregulations of Parkin and PINK1
revealed in cell and animal models of TDP-43 proteinopathy.
Cell Death Dis. 2018
Sep 20;9(10):953. doi: 10.1038/s41419-018-1022-y. PMID: 30237395; PMCID:
PMC6148241.
Kuo YP, Tsai KN, Luo YC, Chung PJ, Su YW, Teng Y, Wu MS, Lin YF, Lai CY,
Chuang TH, Dai SS, Tseng FC, Hsieh CH, Tsai DJ, Tsai WT, Chen CH, Yu GY.
Establishment of a mouse model for the complete mosquito-mediated transmission
cycle of Zika virus.
PLoS Negl Trop Dis. 2018 Apr 18;12(4):e0006417. doi:
10.1371/journal.pntd.0006417. PMID: 29668683; PMCID: PMC5927462.
Yen PS, James A, Li JC, Chen CH, Failloux AB. Synthetic miRNAs induce dual
arboviral-resistance phenotypes in the vector mosquito <i>Aedes aegypti</i>.
Commun Biol. 2018 Feb 8;1:11. doi: 10.1038/s42003-017-0011-5. PMID: 30271898;
PMCID: PMC6053081.
2017
Wu RH, Tsai MH, Tsai KN, Tian JN, Wu JS, Wu SY, Chern JH, Chen CH, Yueh A.
Mutagenesis of Dengue Virus Protein NS2A Revealed a Novel Domain Responsible for
Virus-Induced Cytopathic Effect and Interactions between NS2A and NS2B
Transmembrane Segments
. J Virol. 2017 May 26;91(12):e01836-16. doi:
10.1128/JVI.01836-16. PMID: 28381578; PMCID: PMC5446631.
2016
Lai YW, Chu SY, Wei JY, Cheng CY, Li JC, Chen PL, Chen CH, Yu HH. Drosophila
microRNA-34 Impairs Axon Pruning of Mushroom Body γ Neurons by Downregulating
the Expression of Ecdysone Receptor.
Sci Rep. 2016 Dec 23;6:39141. doi:
10.1038/srep39141. PMID: 28008974; PMCID: PMC5180235.
Liu H, Liu T, Xie L, Wang X, Deng Y, Chen CH, James AA, Chen XG. Functional
analysis of Orco and odorant receptors in odor recognition in Aedes albopictus.
Parasit Vectors. 2016 Jun 27;9(1):363. doi: 10.1186/s13071-016-1644-9. PMID:
27350348; PMCID: PMC4924234.
2015
20: Tsai KN, Chong CL, Chou YC, Huang CC, Wang YL, Wang SW, Chen ML, Chen CH,
Chang C. Doubly Spliced RNA of Hepatitis B Virus Suppresses Viral Transcription
via TATA-Binding Protein and Induces Stress Granule Assembly.
J Virol. 2015
Nov;89(22):11406-19. doi: 10.1128/JVI.00949-15. Epub 2015 Sep 2. PMID: 26339052;
PMCID: PMC4645676.
2014
Liang CJ, Chang YC, Chang HC, Wang CK, Hung YC, Lin YE, Chan CC, Chen CH,
Chang HY, Sang TK. Derlin-1 regulates mutant VCP-linked pathogenesis and
endoplasmic reticulum stress-induced apoptosis.
PLoS Genet. 2014 Sep
25;10(9):e1004675. doi: 10.1371/journal.pgen.1004675. PMID: 25255315; PMCID:
PMC4177747.
Obata F, Kuranaga E, Tomioka K, Ming M, Takeishi A, Chen CH, Soga T, Miura
- Necrosis-driven systemic immune response alters SAM metabolism through the
FOXO-GNMT axis.
Cell Rep. 2014 May 8;7(3):821-33. doi:
10.1016/j.celrep.2014.03.046. Epub 2014 Apr 17. PMID: 24746817.
2013
Tang HW, Liao HM, Peng WH, Lin HR, Chen CH, Chen GC. Atg9 interacts with
dTRAF2/TRAF6 to regulate oxidative stress-induced JNK activation and autophagy
induction.
Dev Cell. 2013 Dec 9;27(5):489-503. doi:
10.1016/j.devcel.2013.10.017. Epub 2013 Nov 21. PMID: 24268699.
Lee G, Sehgal R, Wang Z, Nair S, Kikuno K, Chen CH, Hay B, Park JH.
Essential role of grim-led programmed cell death for the establishment of
corazonin-producing peptidergic nervous system during embryogenesis and
metamorphosis in Drosophila melanogaster.
Biol Open. 2013 Mar 15;2(3):283-94.
doi: 10.1242/bio.20133384. Epub 2013 Jan 17. PMID: 23519152; PMCID: PMC3603410.
2012
Akbari OS, Chen CH, Marshall JM, Huang H, Antoshechkin I, Hay BA. Novel
synthetic Medea selfish genetic elements drive population replacement in
Drosophila; a theoretical exploration of Medea-dependent population suppression.
ACS Synth Biol. 2014 Dec 19;3(12):915-28. doi: 10.1021/sb300079h. Epub 2012 Dec
- PMID: 23654248; PMCID: PMC3742681.
2011
Lee G, Wang Z, Sehgal R, Chen CH, Kikuno K, Hay B, Park JH. Drosophila
caspases involved in developmentally regulated programmed cell death of
peptidergic neurons during early metamorphosis.
J Comp Neurol. 2011 Jan
1;519(1):34-48. doi: 10.1002/cne.22498. PMID: 21120926.
2010
Hay BA, Chen CH, Ward CM, Huang H, Su JT, Guo M. Engineering the genomes of
wild insect populations: challenges, and opportunities provided by synthetic
Medea selfish genetic elements
. J Insect Physiol. 2010 Oct;56(10):1402-13. doi:
10.1016/j.jinsphys.2010.05.022. Epub 2010 Jun 9. PMID: 20570677; PMCID:
PMC3601555.
37: Siegrist SE, Haque NS, Chen CH, Hay BA, Hariharan IK. Inactivation of both
Foxo and reaper promotes long-term adult neurogenesis in Drosophila.
Curr Biol.
2010 Apr 13;20(7):643-8. doi: 10.1016/j.cub.2010.01.060. Epub 2010 Mar 25. PMID:
20346676; PMCID: PMC2862284.
2009
Chen CH, Sun YH, Pei DS, Zhu ZY. Comparative expression of zebrafish lats1
and lats2 and their implication in gastrulation movements.
Dev Dyn. 2009
Nov;238(11):2850-9. doi: 10.1002/dvdy.22105. PMID: 19842174.
Yu HH, Chen CH, Shi L, Huang Y, Lee T. Twin-spot MARCM to reveal the
developmental origin and identity of neurons.
Nat Neurosci. 2009
Jul;12(7):947-53. doi: 10.1038/nn.2345. Epub 2009 Jun 14. PMID: 19525942; PMCID:
PMC2701974.
2008
Sathyanarayanan S, Zheng X, Kumar S, Chen CH, Chen D, Hay B, Sehgal A.
Identification of novel genes involved in light-dependent CRY degradation
through a genome-wide RNAi screen.
Genes Dev. 2008 Jun 1;22(11):1522-33. doi:
10.1101/gad.1652308. PMID: 18519643; PMCID: PMC2418588.
Yao JG, Weasner BM, Wang LH, Jang CC, Weasner B, Tang CY, Salzer CL, Chen
CH, Hay B, Sun YH, Kumar JP. Differential requirements for the Pax6(5a) genes
eyegone and twin of eyegone during eye development in Drosophila.
Dev Biol. 2008
Mar 15;315(2):535-51. doi: 10.1016/j.ydbio.2007.12.037. Epub 2008 Jan 4. PMID:
18275947; PMCID: PMC2702218.
2007
Shcherbata HR, Ward EJ, Fischer KA, Yu JY, Reynolds SH, Chen CH, Xu P, Hay
BA, Ruohola-Baker H. Stage-specific differences in the requirements for germline
stem cell maintenance in the Drosophila ovary.
Cell Stem Cell. 2007 Dec
13;1(6):698-709. doi: 10.1016/j.stem.2007.11.007. PMID: 18213359; PMCID:
PMC2211735.
Chen CH, Huang H, Ward CM, Su JT, Schaeffer LV, Guo M, Hay BA. A synthetic
maternal-effect selfish genetic element drives population replacement in
Drosophila.
Science. 2007 Apr 27;316(5824):597-600. Epub 2007 Mar 29. PMID:
17395794.
Huh JR, Foe I, Muro I, Chen CH, Seol JH, Yoo SJ, Guo M, Park JM, Hay BA. The
Drosophila inhibitor of apoptosis (IAP) DIAP2 is dispensable for cell survival,
required for the innate immune response to gram-negative bacterial infection,
and can be negatively regulated by the reaper/hid/grim family of IAP-binding
apoptosis inducers.
J Biol Chem. 2007 Jan 19;282(3):2056-68. doi:
10.1074/jbc.M608051200. Epub 2006 Oct 26. PMID: 17068333.
2006
Chen CH, Guo M, Hay BA. Identifying microRNA regulators of cell death in
Drosophila.
Methods Mol Biol. 2006;342:229-40. doi: 10.1385/1-59745-123-1:229.
PMID: 16957378.
Muro I, Berry DL, Huh JR, Chen CH, Huang H, Yoo SJ, Guo M, Baehrecke EH, Hay
- The Drosophila caspase Ice is important for many apoptotic cell deaths and
for spermatid individualization, a nonapoptotic process.
Development. 2006
Sep;133(17):3305-15. doi: 10.1242/dev.02495. Epub 2006 Aug 3. PMID: 16887831.
Chen CH, Kao DI, Chan SP, Kao TC, Lin JY, Cheng SC. Functional links between
the Prp19-associated complex, U4/U6 biogenesis, and spliceosome recycling.
RNA.
2006 May;12(5):765-74. doi: 10.1261/rna.2292106. Epub 2006 Mar 15. PMID:
16540691; PMCID: PMC1440898.
1999-2005
Chen, H.-R., Tsao, T.-Y.,
Chen, C.-H., Tsai, W.-Y., Her, L.-S., Hsu, M.-T. and Cheng, S.-C*. (1999) Snt309p modulates interactions of Prp19p with its associated components to stabilize a protein complex essential for pre-mRNA splicing.
Proc. Natl. Acad. Sci. USA 96, 5406-5411.
IF=10.260; 3/52/Multidisciplinary Sciences/Q1/95.192
Tsai, W.-Y., Chow, I.-T., Chen, H.-R., Huang, K.-T., Hong, R.-I., Jan, S.-P., Kuo, N.-Y., Tsao, T.-Y.,
Chen, C.-H., and Cheng, S.-C*. (1999) Cef1p is a component of the Prp19p-associated complex and essential for pre-mRNA splicing.
J. Biol. Chem. 274, 9455-9462.
IF=7.666; 22/295/Biochemistry & Molecular Biology/Q1/92.712
Chen, C.-H., Tsai, W.-Y., Chen, H.-R., Wang, C.-H., and Cheng, S,-C*. (2001) Identification and characterization of two novel components of the Prp19p-associated complex, Ntc30p and Ntc20p.
J. Biol. Chem. 276: 488-494.
IF=7.258; 29/308/Biochemistry & Molecular Biology/Q1/90.747
Chen, C.-H., Yu, W.-C., Taso, T.-Y., Wang, L.-Y., Chen, H.-R., Lin, J.-Y., Tsai, W.-Y., and Cheng, S,-C*. (2002) Functional and physical interactions between components of the Prp19p-associated complex.
Nucleic Acid Research 30:1029-1037.
IF=7.051; 25/266/Biochemistry & Molecular Biology/Q1/90.789
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