National University of Singapore - Interview with InTech's author Ass. Prof. Justin Jang Hann CHU
August 25, 2015
The National University of Singapore (NUS) has recently been placed among the top universities in terms of reputation standings in Thomson Reuters' 2015 Academic Reputation Survey. It is also considered as one of the best universities on a global level, placing 22nd in the world and 1st in Asia in the 2014 QS rankings. The Academic Ranking of World Universities (ARWU) consistently placed NUS in the range of 100–150 worldwide. NUS has three Research Centres of Excellence (RCE) and 22 university-level institutes and centres and is well-known for its research strengths in engineering, life sciences and biomedicine, social sciences and natural sciences.
InTech has had the opportunity to work with authors and editors from this fast growing institution throughout the years. In view of these successful collaborations, we would like to highlight a series of InTech books featuring researchers from NUS, and give a more comprehensive insight into the work of one of our authors affiliated with NUS, Assistant Professor Justin Jang Hann CHU.
NU of Singapore Authors/Editors
InTech has published and collaborated with 52 authors and editors from NUS. Some of the book titles include:
To browse through the list of InTech's National University of Singapore collaborators and view their respective book chapters or edited volumes, follow the link.
We recently had the chance to speak with Assistant Professor Justin Jang Hann CHU from the Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology (NUS).
Prof. Chu co-authored 2 chapters respectively published in the books titled “Flavivirus Encepahalitis” (InTech, 2011), and “Encephalitis” (InTech, 2013). We took the opportunity to ask him about his research, his professional career and working with us. (read more)
InTech: You have co-authored 2 chapters published in our books, respectively titled Dengue Encephalitis (2011), and Viral Encephalitis with Focus on Human Enteroviruses (2013). What does your research specifically focuses on?
Prof. Chu: Our research focuses on several clinically significant RNA viruses, such as the dengue virus, enterovirus-71, and chikungunya virus. Our aim is to study these viruses and to develop anti-viral strategies to counter these viruses.
InTech: What are positive-strand RNA virus and its effect on humans?
Prof. Chu: Typically, the genome of organisms like animals, plants, fungi and bacteria consists of double-stranded DNA. These two strands are composed of a positive-sense and negative-sense strand. The positive-strand RNA viruses are a diverse group of viruses whose genomes consist of positive-sense, single-stranded of RNA.
This diverse group can be further subdivided into many different families. For example, the yellow fever virus, dengue virus, West Nile virus, Japanese encephalitis virus and the hepatitis C virus all belong to the Flaviviridae family while the rhinoviruses, enterovirus-71 and poliovirus belong to the Picornaviridae family.
Generally speaking, the effect of a virus on humans depends on its virulence and its pathogenicity. This refers to the virus’s ability to infect the various organs and tissues of a human, and the morbidity or disease state that arises as a result of that infection. The symptoms of the disease itself is a combined result of the virus actively causing damage to human tissue and the infected human’s immune system unleashing potent biochemical weapons to combat the virus. For example, the poliovirus, enterovirus-71 and West Nile virus are neurotropic viruses that can infect nerve cells, and as such they may cause encephalitis. The rhinovirus typically infects the upper respiratory tract and it is the most common cause of the common cold, while the hepatitis C virus primarily infects liver cells and is a significant cause of liver cirrhosis and liver cancer in countries such as Egypt and Japan.
InTech: How spread are these viruses among the world population?
Prof. Chu: The global distribution of a virus and its prevalence within specific regions is dependent on several factors, chief of which is the mode of transmission. The dengue virus is mainly transmitted from human to human via the Aedes aegypti mosquito, which is found in tropical and sub-tropical regions. As a result, while there are an estimated 400 million dengue virus infections per year, these infections are limited to people in the tropical and sub-tropical regions. On the other hand, the rhinovirus, which is the most common cause of the common cold, does not need an insect vector. Instead, it is easily transmitted from human to human through the air, and can also be transmitted through contact with contaminated surfaces. As such, the common cold is one of the most common infections in the world, and is not limited by any geographical boundary.
Another important factor that determines virus distribution is the reservoir of the virus. Humans are the only known reservoir of the poliovirus. As such, widespread vaccination against poliovirus has led to the eradication of polio from many parts of the world and reintroduction is only possible from the few places where the humans are still infected with the poliovirus. On the other hand, birds are the main animal reservoir of the West Nile virus and it is mainly transmitted from birds to humans via mosquitoes. In the temperate regions of the USA that are affected by the West Nile virus, the human population typically remains free of West Nile Virus infections during the winter months when the mosquito vector is inactive. However, during the warmer months, when the mosquito vector becomes active again, the virus is re-introduced into the human population.
InTech: How far have we come in terms of finding a viable vaccine against positive-strand RNA viruses?
Prof. Chu: There are many vaccines currently available for positive-strand RNA viruses, such as the yellow fever virus, Japanese encephalitis virus and the poliovirus. There are also many vaccines that are currently undergoing development and testing. In particular, vaccines against the dengue virus and against enterovirus-71 have recently undergone clinical testing.
One factor which complicates vaccine development is the need to develop vaccines against viruses which exist as multiple serotypes. Typically, protective immunity against one serotype does not confer protective against another. For example, there are three serotypes of poliovirus, and the poliovirus vaccines that were originally developed by Salk and Sabin are essentially a combination of three different vaccines, one for each serotype. On the other hand, there are more than 90 serotypes of the rhinovirus, and as such a combination vaccine against all the rhinovirus serotypes is deemed impractical. Instead, efforts are being made to develop a single vaccine that confers pan-serotype protection.
As another example, there are 4 serotypes of dengue virus, and the recently tested Sanofi Pasteur dengue virus combination vaccine was found to confer a lower degree of protective immunity against dengue serotype 2. This is potentially problematic as immunity against one dengue virus serotype is a risk factor for increased disease severity during infection with another dengue virus serotype.
InTech: How much time does it pass before research findings are tested and translated into medicines by pharmaceutical companies and commercialized?
Prof. Chu: The process of drug development is a long and expensive process, especially at the clinical evaluation phase. This process typically takes more than 10 years, and the failure rate is disproportionate to the drugs which are eventually approved. Because of this, drug companies may find it commercially unprofitable to develop anti-viral drugs against less significant viruses, or against viruses which are predominantly found in developing countries.
Drug repurposing represents a method of speeding up the development of anti-viral therapeutics. Under this scheme, clinically tested or clinically approved drugs are tested for their potential use in anti-viral therapeutics. This offers the advantage of allowing the development of the drug to be fast-tracked, as it has already gone through the clinical testing phase.
InTech: In general, do you think that publishing in open access leads to spreading information faster and eventually speeding up research on a global level?
Prof. Chu: Typically, a researcher gains access to scientific publications through a subscription paid for by his or her parent institute. However, institutions may find it too expensive to offer subscriptions to the vast numbers of journals and publications in existence. This is especially the case for institutions in developing countries. Open access publication allows researchers in these institutions to keep up to date with current research trends and methodologies.
InTech: What do you consider to be your most important milestone career-wise?
Prof. Chu: Having identified important cellular factors that are essential for the replication of a number of medically important viruses are important breakthrough in my scientific career. By understanding how the essential cellular factors can affect virus replication are important targets for antiviral strategies development. The cellular receptor, integrin alphaV beta 3 (1) and the interacting domain counterpart (2) of West Nile virus (Sarafend) were identified and these studies have fuel the development of vaccines (3) and antivirals to target the mosquito borne West Nile virus.
More recently, we have made a first by showing the role of Misshapen NCK-related kinase (MINK), a novel Ste20 family kinase in the IRES-mediated protein translation of human enterovirus 71, published in PLoS Pathogens (4). These novel findings hence suggest that MINK plays a functional role in the IRES-mediated translation of EV71 viral RNA and may provide a potential target for the development of specific antiviral strategies against EV71 infection.
- Chu JJ, Ng ML. Interaction of West Nile virus with alpha v beta 3 integrin mediates virus entry into cells. J Biol Chem. 2004 Dec 24;279(52):54533-41.
- Chu JJ, Rajamanonmani R, Li J, Bhuvanakantham R, Lescar J, Ng ML. Inhibition of West Nile virus entry by using a recombinant domain III from the envelope glycoprotein. J Gen Virol. 2005 Feb;86(Pt 2):405-12.
- Chu JJ, Chiang CC, Ng ML. Immunization of flavivirus West Nile recombinant envelope domain III protein induced specific immune response and protection against West Nile virus infection. J Immunol. 2007 Mar 1;178(5):2699-705.
- Leong SY, Ong BK, Chu JJ. The role of Misshapen NCK-related kinase (MINK), a novel Ste20 family kinase, in the IRES-mediated protein translation of human enterovirus 71. PLoS Pathog. 2015 Mar 6;11(3):e1004686.
InTech: What are you currently working on?
Prof. Chu: Positive-strand RNA viruses encompass over one-third of all virus genera and include numerous human pathogens, such as dengue virus, West Nile virus, Enterovirus 71, Chikungunya virus SARS coronavirus and hepatitis C virus. Host factors participate in most, if not all steps of positive-strand RNA virus infection, including entry, viral gene expression, virion assembly and release. Moreover, host factors are targeted by positive-strand RNA viruses to modulate host gene expression and immune defenses. In our current study, human Enterovirus 71, Dengue virus and Chikungunya virus are used as the virus models to decipher the interplay of essential host factors with positive-strand RNA viruses. Knowledge gained from these investigations will facilitate formulation of effective vaccine or therapeutic intervention against these medically important virus infections and possibly other pathogenic positive-strand RNA viruses.
Finally, when asked about the rising academic reputation of NUS and current research focuses across the many university facilities, Dr. Chu pointed out the very much fertile ground for a number of disciplines leading the way in terms of important research output. Among other we find particular emphasis on themes such as integrated sustainability solutions for energy, water and the environment; ageing populations; biomedical sciences and translational medicine; global-Asian studies; finance and risk management; and materials science. In 2013, NUS had more than 2,400 research active faculty who produced over 8,000 publications and filed close to 520 patents and over 340 invention disclosures. Moreover, NUS faculty serve as consultants and advisors to more than 50 industry and government bodies. Several leading companies have also chosen to establish research labs and partnerships at NUS including Siemens, GE, Zeiss and Agilent. To find out more about NUS, its program and research, please click here.
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