Justin Chu

Collaborative Translation Unit for Hand, Foot and Mouth Disease

Profile

Justin CHU
Lab Location: #6-06B   Email: jhchu@imcb.a-star.edu.sg   Tel: 65869656

Associate Professor Justin Chu is currently a faculty member in the Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore.  He is holding a joint appointment Principal Investigator in the Institute of Molecular and Cell Biology, A*STAR.  A/P Chu is also the director of the largest research based high containment Biosafety Level 3 Facility in Singapore which is located in the Yong Loo Lin School of Medicine, NUS.  A/P Chu is actively engaged in the study of the molecular biology of human enteroviruses as well as mosquito-borne viruses including Dengue, Zika, West Nile/Japanese Encephalitis and Chikungunya.  The outcome of these studies have helped to pave the roadmap towards the development of a number of antiviral strategies (antivirals, vaccines, therapeutics antibodies, molecular inhibitors) that are now in the process of clinical translational evaluation for these medically important mosquito-borne viruses. Eight patents have also been generated from these current research.

A/P Chu has published over 90 international peer-reviewed scientific publications, book chapters and over 100 conference papers.  A number of these scientific papers are published in prestigious journals including Nature Communications, PNAS, PLoS Pathogens, Biomaterials, Journal of Biological Chemistry, Journal of Virology and Antiviral therapy. A/P Chu is currently serving as the associate editor and reviewer for a number of peer-reviewed journals in the areas of medical virology and anti-viral strategies.

Research

Translational Anti-Enteroviral Research

Hand, foot and mouth disease (HFMD) is generally a mild disease characterized by a low-grade fever accompanied by skin lesion on the limbs and mouth in young children. However, it can also result in complications leading to fatality. A plethora of viruses from the genus Enterovirus have been associated with HFMD to date. Major outbreaks have been occurring throughout the region in cycles of two to three years intervals in recent years, each outbreak being characterized by slightly different serotypes of viruses, with the most common being human enterovirus 71 (EV-71) and coxsackievirus A16 (CVA16). Although most HFMD cases are mild, the increasing frequency and severity of recent outbreaks, with a number of them reaching epidemic levels, the disease is emerging as a major public health concern in the region, including Singapore.

Despite the associated health risks and threat of HFMD to public health, there is no vaccine or therapeutic regime available. This is compounded by the limited research progress in understanding enteroviruses in the last 20 years after the eradication of poliomyelitis in most countries. Hence, the objective of the laboratory is to develop novel and effective anti-viral strategies against HFMD-causing enteroviruses while at the same time understanding the biology of this diverse group of viruses to fuel translational anti-enteroviral research.

High throughput antiviral screens and animal model of infection for human enteroviruses

The laboratory has established highly versatile cell-based high throughput screens for human enteroviruses and specializes in the evaluation of therapeutic molecules or vaccine candidates in established murine model of enteroviral infection. We seek collaborations in the following areas: 

· Evaluation of antiviral strategies (antiviral molecules, vaccine candidates, molecular genomics and nanotechnology) against HFMD.
· Validation of antiviral or vaccine candidates in our established enteroviral animal model.
· Development of novel diagnostics approaches for human enteroviruses.



Our industry research collaboration partners include Z Group Global Pte. Ltd and ESCO Aster.

In addition to research collaborations, our laboratory offers laboratory evaluation of virucidal/disinfectant materials and has worked with established companies by evaluating candidate prototypes against different viruses. Virucide/disinfectant evaluation service is available against a wide range of viruses available in our virus repository. 

Staff

Department: Justin Chu

Name: Chwee Fern BOK

Designation: Laboratory Officer

Email: bokcf@imcb.a-star.edu.sg


Name: Rachel Jia Wen KOOI

Designation: Reseach Fellow

Email: rjwkooi@imcb.a-star.edu.sg


Name: Yong Wah TAN

Designation: Research Fellow

Email: ywtan@imcb.a-star.edu.sg


Publications

Dr. Justin Chu’s Representative Publications

Min N, Sakthi Vale PD, Wong AA, Tan NWH, Chong CY, Chen CJ, Wang RYL, Chu JJH (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.

Teo FMS, Nyo M, Wong AA, Tan NWH, Koh MT, Chan YF, Chong CY, Chu JJH (2018). 
Cytokine and Chemokine Profiling in Patients with Hand, Foot and Mouth Disease in Singapore and Malaysia.
Scientific Reports. 8(1):4087.

Too IHK, Bonne I, Tan EL, Chu JJH, Alonso S (2018). 
Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis. 
PLoS Pathogens. 14(1):e1006778.

Min N, Leong PT, Lee RCH, Khuan JSE, Chu JJH (2018). 
A flavonoid compound library screen revealed potent antiviral activity of plant-derived flavonoids on human enterovirus A71 replication. 
Antiviral Research. 150:60-68.

Tan YW, Yam WK, Sun J, Chu JJH (2018). 
An evaluation of Chloroquine as a broad-acting antiviral against Hand, Foot and Mouth Disease.
Antiviral Research. 149:143-149.

Wu KX, Chu JJ (2017). 
Antiviral screen identifies EV71 inhibitors and reveals camptothecin-target, DNA topoisomerase 1 as a novel EV71 host factor. 
Antiviral Research. 143:122-133. 

Reyes M, Piotrowski M, Ang SK, Chan J, He S, Chu JJH, Kah JCY (2017). 
Exploiting the Anti-Aggregation of Gold Nanostars for Rapid Detection of Hand, Foot, and Mouth Disease Causing Enterovirus 71 Using Surface-Enhanced Raman Spectroscopy. 
Analytical Chemistry. 89(10):5373-5381.
 
Wu KX, Phuektes P, Kumar P, Goh GY, Moreau D, Chow VT, Bard F, Chu JJ (2016). 
Human genome-wide RNAi screen reveals host factors required for enterovirus 71 replication. 
Nature Communications. 7:13150. 

Tan YW, Ang MJ, Lau QY, Poulsen A, Ng FM, Then SW, Peng J, Hill J, Hong WJ, Chia CS, Chu JJ (2016). 
Antiviral activities of peptide-based covalent inhibitors of the Enterovirus 71 3C protease. 
Scientific Reports. 6:33663.

Sun J, Ennis J, Turner JD, Chu JJ (2016). 
Single dose of an adenovirus vectored mouse interferon-α protects mice from lethal EV71 challenge. 
Antiviral Research. 134:207-215. 

Tan YW, Hong WJ, Chu JJ (2016). 
Inhibition of enterovirus VP4 myristoylation is a potential antiviral strategy for hand, foot and mouth disease. 
Antiviral Research. 133:191-195.

Teo FM, Chu JJ (2016). 
Diagnosis of human enteroviruses that cause hand, foot and mouth disease. 
Expert Review of Anti-infective Therapy. 14(5):443-445.

Ang MJ, Lau QY, Ng FM, Then SW, Poulsen A, Cheong YK, Ngoh ZX, Tan YW, Peng J, Keller TH, Hill J, Chu JJ, Chia CS (2016). 
Peptidomimetic ethyl propenoate covalent inhibitors of the enterovirus 71 3C protease: a P2-P4 study. 
Journal of Enzyme Inhibition and Medicinal Chemistry. 31(2):332-339.
 
Chen H, Parimelalagan M, Takei F, Hapuarachchi HC, Koay ES, Ng LC, Ho PS, Nakatani K, Chu JJH (2016). 
Development of 2, 7-Diamino-1, 8-Naphthyridine (DANP) Anchored Hairpin Primers for RT-PCR Detection of Chikungunya Virus Infection. 
PLoS Neglected Tropical Diseases. 10(8): e0004887.

Clark MJ, Miduturu C, Schmidt AG, Zhu X, Pitts JD, Wang J, Potisopon S, Zhang J, Wojciechowski A, Chu JJH, Gray NS, Yang PL (2016). 
GNF-2 Inhibits Dengue Virus by Targeting Abl Kinases and the Viral E Protein. 
Cell Chemical Biology. 23(4):443-452.

Leong SY, Ong BK, Chu JJ (2015). 
The role of Misshapen NCK-related kinase (MINK), a novel Ste20 family kinase, in the IRES-mediated protein translation of human enterovirus 71. 
PLoS Pathogens. 11(3):e1004686.

Lam S, Nyo M, Phuektes P, Yew CW, Tan YJ, Chu JJH (2015). 
A potent neutralizing IgM mAb targeting the N218 epitope on E2 protein protects against Chikungunya virus pathogenesis. 
MAbs. 7(6):1178- 94.

Chen J, Ng MM, Chu JJH (2015). 
Activation of TLR2 and TLR6 by Dengue NS1 Protein and Its Implications in the Immunopathogenesis of Dengue Virus Infection. 
PLoS Pathogens. 11(7):e1005053.

Teo CS, Chu JJH (2014). Cellular Vimentin Regulates Construction of Dengue Virus Replication Complexes through the Interaction with NS4A Protein. 
Journal of Virology. 88(4):1897-1913.

Lee RC, Hapuarachchi HC, Chen KC, Hussain KM, Chen H, Low SL, Ng LC, Lin R, Ng MM, Chu JJH (2013).
Mosquito Cellular Factors and Functions in Mediating the Infectious entry of Chikungunya Virus.
PLoS Neglected Tropical Diseases. 7(2):e2050.

Chen H, Takei F, Koay ES, Nakatani K, Chu JJH (2013). A Novel DANP-Coupled Hairpin RT-PCR for Rapid Detection of Chikungunya Virus.
Journal of Molecular Diagnostics. 15(2):227-233.

Kaur P, Thiruchelvan M, Lee RC, Chen H, Chen KC, Ng ML, Chu JJH (2013).
Inhibition of chikungunya virus replication by harringtonine, a novel antiviral that suppresses viral protein expression.
Antimicrobial Agents and Chemotherapy. 57(1):155-167.

Zhao Y, Howe JL, Yu Z, Leong DT, Chu JJH, Loo JS, Ng KW (2013).
Exposure to titanium dioxide nanoparticles induces autophagy in primary human keratinocytes.
Small. 9(3):387-392.

Chia PY and Chu JJH* (2012),
Viral Encephalitis with Focus on Human Enteroviruses.
Encephalitis edited by Sergey Tkachev, ISBN 978-953-51-0925-9, ISBN 980-953-30 ed. Intech Publisher, 2012.

Lam S, Chen KC, Ng MM, Chu JJH (2012).
Expression of plasmid-based shRNA against the E1 and nsP1 genes effectively silenced Chikungunya virus replication.
PLoS One. 7(10):e46396.

Ong SP, Lee LM, Leong YF, Ng ML, Chu JJH (2012).
Dengue virus infection mediates HMGB1 release from monocytes involving PCAF acetylase complex and induces vascular leakage in endothelial cells.
PLoS One. 7(7):e41932.

Karuppannan AK, Wu KX, Qiang J, Chu JJH, Kwang J (2012).
Natural compounds inhibiting the replication of Porcine reproductive and respiratory syndrome virus.
Antiviral Research. 94(2):188-194.

Lim ME, Lee YL, Zhang Y and Chu JJH (2011).
Photodynamic inactivation of viruses using upconversion nanoparticles. 
Biomaterials. 33(6):1912-1920.

Low JSY, Wu KX, Chen KCY, Ng MML and Chu JJH (2011).
Narasin, a novel antiviral compound that inhibits dengue virus protein expression. 
Antiviral Therapy, 16(8): 1203‑1218.

Hussain MK and Chu JJH (2011).
Insights into the interplay between chikungunya virus and its human host.  
Future Virology
, 6(10): 1211‑1223. 

Leong JYS, Ng MML and Chu JJH (2011).
Replication of Alphaviruses ‑ A Review on the Entry Process of Alphaviruses into Cells. 
Advances in Virology
, Article ID No. 249640.

Ong SP and Chu JJH (2011).
An update on the host factors contributing to vascular leakage during dengue virus infection. (Invited Editorial) 
Future Virology
, 6(2): 135-138 (Invited Editorial).

Hussain KM, Leong KL, Ng MM and Chu JJH (2011).  
The essential role of clathrin-mediated endocytosis in the infectious entry of human Enterovirus 71. 
Journal of Biological Chemistry,
 286(1):309-321. 

Wu KX, Ng MM and Chu JJH (2010).
Developments towards antiviral therapies against Enterovirus 71. 
Drug Discov Today, 15 (23-24):1041-1051.

Chia PY, Ng ML and Chu JJH (2010).
Chikungunya fever: A review of a re-emerging mosquito-borne infectious disease and the current status. 
Current Research, Technology and Education Topics in Applied Microbiology and Microbial Biotechnology. (1): 597-606.

Chen KCY, Ong HM and Chu JJH (2010).
Morphogenesis of Human Enterovirus 71: An Electron Microscopy Analysis Coupled with Immunogold Labelling Techniques. 
Microscopy: Science, Technology, Applications and Education, 
(1): 66-74.
  
Chen JC, Chia PY, Ng ML and Chu JJH (2010).
Antiviral Immunotherapy for mosquito-borne flaviviruses: a review of current status. 
Immunology, Endocrine and Metabolic Agents in Medicinal Chemistry,
 
10(1), 31-42.  

Ang F, Wong AP, Ng L and Chu JJH (2010).
Small interference RNA profiling reveals the essential role of human membrane trafficking genes in mediating the infectious entry of dengue virus.
Virology Journal
,
 7:24. 

Ho PS, Ng ML, Chu JJH (2010).
Establishment of one-step SYBR green-based real time-PCR assay for rapid detection and quantification of chikungunya virus infection. 
Virology Journal
,
7:13.

Azlinda, BA, Leong KW, Ng ML, Chu JJH and Garcia-Blanco MA (2009)
The polypyrimidine tract binding protein is required for efficient dengue virus propagation and associates with the viral replication machinery. 
Journal of Biological Chemistry, 284: 17021-17029.

Low JSY, Chen CK, Wu K, Ng ML and Chu JJH (2009) 
Antiviral Activity of Emetine Dihydrochloride against Dengue Virus Infection. 
Journal of Antivirals and Antiretrovirals, 1(1): 062-071.

Lee YL, Ng ML, Zhang Y and Chu JJH (2009). 
Novel photodynamic therapy of emerging and re-emerging medically important viruses. 
Asia Pacific Biotechnology
13(3), 24-27.  

Chen JC, Ng ML and Chu JJH (2009). 
Molecular Profiling of T-Helper genes in mediating immunopathogenesis of dengue virus infection. 
Virology Journal5:165. 

Ong SP, Chu JJH and Ng ML (2008). 
Inhibition of West Nile virus replication in cells stably transfected with vector-based shRNA expression system. 
Virus Research,
 135(2): 292-297. 

Hwang YC, Chu JJH, Yang PL, Chen W and Yates MV (2008). 
Rapid identification of inhibitors that interfere with poliovirus replication using a cell-based assay.  
Anti-Viral Research, 77(3): 232-236. 

Chu JJH and Ng ML (2008). 
Interplay of viral and host cellular factors in West Nile virus replication and pathogenesis.  
Future Virology, 3(1), 17-23.

Chu JJH and Yang PL (2007) 
c-Src protein kinase inhibitors block the assembly and maturation of dengue virus. 
Proc. Natl. Acad. Sci. USA. 
104:3520-3525.

Chu JJH, Chiang CC and Ng ML (2007) 
Immunization of West Nile virus envelope glycoprotein domain III induced specific immune responses and protection against West Nile infection. 
J. Immunol. 
178:2699-2705.

Chin JF, Chu JJH and Ng ML (2007) 
The envelope glycoprotein domain III of Dengue virus serotypes 1 and 2 inhibit virus entry.
Microbes and Infect.
 
9:1-6.

Ong SP, Choo BGH, Chu JJH and Ng ML (2006) 
A vector-based small interfering RNA against West Nile virus infection.  
Anti-Viral Research,
 72:216-223.

Chu JJH, Leong PWH and Ng ML (2006) 
Analysis of the endocytic pathway mediating the infectious entry of mosquito-borne flavivirus West Nile into Aedes albopictus mosquito cells.
Virol. 
349:463-475.

Lee JWM, Chu JJH and Ng ML (2006) 
Quantifying the specific binding between West Nile virus envelope domain III protein and the cellular receptor αVβ3 integrin. 
J. Biol. Chem. 281:1352-1360.
 
Chu JJH, Leong PWH and Ng ML (2005) 
Characterization of plasma membrane associated proteins from Aedes Albopictus mosquito (C6/36) cells that mediate West Nile virus binding and infection. 
Virol.
 339:249-260.

Chu JJH, Rajamanomani R, Li, J, Bhuvanakanathan R, Lescar J and Ng ML. (2005) 
Inhibition of West Nile virus entry using a recombinant domain III from envelope glycoprotein. 
J. Gen. Virol.
 86:405-412.

Chu JJH and Ng ML (2004) 
Interaction of West Nile virus with αVβ3 integrin mediates virus entry into cells. 
J. Biol. Chem.
279:54533-54541.

Chu JJH and Ng ML (2004)
Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway
J. Virol. 78:10543-10555.