• Doctor of Philosophy: The University of Hong Kong, Hong Kong, China
• Master of Science in Pathology: Western University, London, Ontario, Canada
• Bachelor of Science (Honours) in Life Sciences: Queen's University, Kingston, Ontario, Canada (first class honor)

1. Silver Award, HKUST - Sino One Million Dollar Entrepreneurship Competition
   Finalist, Young Scientist Awards
2. Graduate Student Travel Scholarship, Tech Dragon Limited
3. Croucher-Butterfield Studentship, Croucher Foundation

Our research focuses on adopting and developing our own state-of-the-art technologies to study RNA viruses, with an emphasis on Orthomyxoviridae (e.g. influenza A and B viruses), Coronaviridae (e.g. SARS-CoV, SARS-CoV-2) and recently on Flaviviridae (Zika, Dengue, West Niles viruses). The four main themes of our research are (1) Gene replication, (2) Diagnostics, (3) Vaccine, (4) Antivirals

RNA viruses encode their RNA polymerases to replicate the viral genome. The error-prone transcription process of RNA polymerases is the main driving force for viral genetic diversity essential for adaption to and infection of the host. However, the accuracy of virus transcription must be maintained at a certain threshold for faithful gene expression and protein production. We are interested in understanding the structural basis of how viral polymerases regulate transcription accuracy in RNA viruses and the biological consequences of transcriptional errors during infection. The way virus replicate its genome does not always follow the rules present in the eukaryotic systems. We are also interested in understanding how viral genome replication is regulated. To discover new mechanisms of replication accuracy and regulation, we are developing a novel genomics platform and using Cryogenic Electron Microscopy (Cryo-EM). These fundamental insights are essential in the basic understanding of gene transcription and virus evolution and the biomedical research for the development of antiviral drugs and vaccines for emerging infectious diseases.

By discovering viruses that carry mutations at the polymerase that render the virus replication mutation defective, and hence reduced genetic diversity, we were able to generate novel vaccine variants that do not cause diseases but replicate well during the manufacturing process with no selective pressure. In addition, we employ statistical and experimental approaches to determine the efficacy of COVID-19 vaccine regimens in SARS-CoV-2 and its variants of concerns.

Scientific Milestones

• Discovered the first mutation defective virus with enhanced polymerase activity, challenging the thought that mutation-defective polymerase is usually accompanied by a slower polymerase activity.
• Developed that first nascent RNA sequencing technique with high sequencing accuracy that can also measure polymerase error.
• Reveal the mystery of how eukaryotic polymerase can maintain transcription accuracy without compromising polymerase activity.
• Discovered the first ever mutation-defective (with high replication accuracy) influenza virus.

We employ statistical and experimental approaches to evaluate and improve the diagnostic performances of the clinical detection of nucleic acids of influenza viruses and SARS-CoV-2. We are also developing novel technologies to enhance the sensitivity and specificity for nucleic acid detection for infectious and hereditary diseases by using biochemical and microfluidic techniques.

Scientific Milestones

• We performed the first meta-analysis to demonstrate that accuracy of three types of nucleic acid tests (real time PCR, digital PCR, and LAMP) does not differ significantly. Instead, accuracy depends on specific experimental conditions, implying that more efforts should be directed to optimising the experimental setups for the nucleic acid tests.

We employ statistical and experimental approaches to evaluate and improve the diagnostic performances of the clinical detection of nucleic acids of influenza viruses and SARS-CoV-2. We are also developing novel technologies to enhance the sensitivity and specificity for nucleic acid detection for infectious and hereditary diseases by using biochemical and microfluidic techniques.

Scientific Milestones

• We performed the first meta-analysis to demonstrate that accuracy of three types of nucleic acid tests (real time PCR, digital PCR, and LAMP) does not differ significantly. Instead, accuracy depends on specific experimental conditions, implying that more efforts should be directed to optimising the experimental setups for the nucleic acid tests.

We elucidate the mechanisms of inhibition of gene replication by NTP analog antiviral drugs. We employ structural biology and Molecular Dynamics simulation to understand at atomic level how NTP analog disrupt which step of RNA synthesis carried out by the viral polymerase.

Scientific Milestones

• We were amongst the first to show that Ribavirin can inhibit live SARS-CoV-2 replication
• We elucidated the mechanism at atom level how Remdesivir inhibit viral polymerase translocation.
• We explained how the Favipiravir causes delayed chain termination and induces mutagenesis in viral polymerase by using structural biology and enzymology.
• We discovered the first ribavirin-resistant influenza virus, and such virus was reported to be a mutation-defective virus, the first of its kind.