Research
CHEUNG, Pak Hang Peter

Name : CHEUNG, Pak Hang Peter 張栢恒
Title :
Assistant Professor
Home Department :  Chemical Pathology
Email : ppcheung@cuhk.edu.hk
Phone Number:  (852) 3763 6049
Fax Number:  (852) 2636 5090
Address:
Room 306F, 3/F, Li Ka Shing Medical Sciences Building, Prince of Wales Hospital,
30-32 Ngan Shing Street, Shatin, New Territories, Hong Kong
PI's Website: https://www.cuhk.edu.hk/med/cpy/Research/PeterCheung.htm
PI’s Group Website:  https://cuhk.edu.hk/research/petercheunglab/#/

Biography:

Dr Peter Cheung is currently an Assistant Dean (Research) and Assistant Professor in the Department of Chemical Pathology, Faculty of Medicine at the Chinese University of Hong Kong.

He obtained his bachelor’s and Master's degree from Queen’s University, Canada, and Western University, Canada, respectively, and his doctorate degree from The University of Hong Kong.

Dr Cheung's research interest focuses on using computational, statistical, structural, and enzymological approaches to study viral replications and prevention strategies for infectious diseases.

He is the recipient of numerous awards including the Croucher-Butterfield Ph.D. Scholarship (Croucher Foundation), Best Poster Presentation Award (The University of Hong Kong), and Finalist of the Hong Kong Young Scientist Award (Hong Kong Institution of Science).

He has published extensively in the field of computational and structural biology. His original research findings have been published as first or corresponding authors in leading international journals including those of the Lancet Microbe, BMJ, Nature Catalysis, Nucleic Acids Research, and Nature Communications.

His work has been supported by the Research Grants Committee’s General Research Fund and Collaborative Research Fund, with which he led international efforts to study viral replication of influenza and SARS-CoV-2 replication using structural, computational, and enzymology approaches. 

 

Present Employment:

Assistant Dean (Research), Faculty of Medicine, The Chinese University of Hong Kong

Assistant Professor at Department of Chemical Pathology, The Chinese University of Hong Kong

Previous Employment:

Research Assistant Professor at Department of Chemistry, The Hong Kong University of Science and Technology

Research Assistant Professor at Division of Biomedical Engineering, The Hong Kong University of Science and Technology

Postdoctoral Fellow at Division of Biomedical Engineering, The Hong Kong University of Science and Technology

Research Associate at School of Public Health, University of Hong Kong


Academic Qualifications:

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)


Prizes and Awards:

1.      Tigris Student Travel Scholarship, Tech Dragon Limited
Scholarship intends to award research students who will present their scientific findings at a relevant conference. Award is based on academic merits and achievements.

2.      Best Poster Presentation Award, University of Hong Kong, Faculty of Medicine
Two candidates who presented the best poster in the theme of infectious diseases in the annual graduate symposium were awarded a Certificate of Merit. Presentation was done based on PhD project

3.      Croucher-Butterfield Scholarship, The Croucher Foundation
Best candidate in biological science category to be identified by the Selection Committee for the Croucher study awards. Only 1 out of more than 100 candidates is given to the Biological Sciences.

4.      Best student in HKU-Pasteur Virology Course, HKU-Pasteur Research Center

5.      Western Graduate Research Scholarship, Western University

Research scholarship for M.Sc. student offered by the university

6.      Ontario Graduate Scholarship, The Ministry of Training, Colleges and Universities
“The Ontario Graduate Scholarship recognizes academic excellence in graduate studies at the master's and doctoral levels in all disciplines of academic study."

7.      Translational Breast Cancer Research Traineeship (Research Award), The Pamela Greenaway-Kohlmeier Translational Breast Cancer Unit
"By encouraging bright trainees to focus their research attention in this area to increase the number of highly qualified researchers who are working to solve the problem

8.      Ontario Volunteer Service Award, Ministry of Citizenship and Immigration
"The Ontario Volunteer Service Award recognizes individual volunteers for continuous years of commitment and dedicated service to an organization."


Leading Grants and Projects:

1.    RGC - Collaborative Research Fund

CHEUNG Pak Hang Peter (Lead, Principal Coordinator)

2022 - Present

2.    RGC - General Research Fund

CHEUNG Pak Hang Peter (Lead, Principal Investigator)

2018 - Present

3.    RGC - General Research Fund

CHEUNG Pak Hang Peter (Lead, Principal Investigator)


Specialised Research Area(s):

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

(1)   Gene Replication

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.
(2)   Diagnostics

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.
(3)   Vaccine

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.
(4)   Antivirals

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.


Selected Publications:

1. Au, W. Y. and Cheung, P.P.H*. Effectiveness of heterologous and homologous COVID-19 vaccine regimens: a living systematic review with network meta-analysis. The British Medical Journal (BMJ), 377: e069989, (2022) [Research Article; Impact Factor: 96.216] 
Recommended by F1000Prime

2. Au, W. Y., Ye, C., Briner S.L., Suarez, G.D., Han, J., Xu, X., Park, J.G., Brindley, M.A., Martinez-Sobrido*, L., Cheung, P.P.H*. Systematic comparison between BNT162b2 and CoronaVac in the seroprotection against SARS-CoV-2 Alpha, Beta, Gamma, and Delta variants, Journal of Infection, DOI: 10.1016/j.jinf.2022.02.030, (2022) [Research Article; Impact Factor: 38.637]

3. Suarez, G.D., Suarez D.A., Tang Y.Y.K., Zhang J.-X., Li, J., Nagl, S., Cheung P.P.H.* Uncovering Mechanisms of RT-LAMP Colorimetric SARS-CoV-2 Detection to Improve Assay Reliability, Analytical Methods, DOI: 10.1039/D1AY01395E, (2022) [Research Article; Impact Factor: 3.532]

4. Au, W. Y. and Cheung, P. P. H.*, Diagnostic performances of common nucleic acid tests for SARS-CoV-2 in hospitals and clinics: a systematic review and meta-analysis. The Lancet Microbe, DOI:10.1016/S2666-5247(21)00214-7, (2021) [Research Article; Impact Factor: 86.208]

5. Xu, X., Zhang, L.*, Chu J.T.S., Wang, Y. Chin, A.W.H., Dai, Z., Poon, L.L.M., Cheung, P.P.-H.*, Huang, X.*. A Novel Mechanism of Enhanced Transcription Activity and Fidelity for Influenza A Viral RNA-dependent RNA Polymerase, Nucleic Acids Research, 49 (15), 8796, (2021) [Research Article; Impact Factor: 19.160]

6. Wang, Y., Yuan, C., Xu, X., Chong, T.H., Zhang, L., Cheung P.P.H.*, Huang, X.*. The mechanism of action of T-705 as a unique delayed chain terminator on influenza viral polymerase transcription, Biophysical Chemistry, 277, 106652, (2021) [Research Article; Impact Factor: 3.628]

7. Zhang, L., Zhang, D., Wang X., Yuan, X., Li, Y., Jia, X., Gao, X., Yen, H.L., Cheung, P.P.*, Huang, X.*, 1’-Ribose Cyano Substitution Allows Remdesivir to Effectively Inhibit both Nucleotide Addition and Proofreading during SARS-CoV-2 Viral RNA Replication, Physical Chemistry Chemical Physics, 23, 5852 (2021) [Research Article; Impact Factor: 3.945]
2021 PCCP HOT Articles

8. Wang, Y.*, Chong, T.H.*, Unarta, I.C.*, Xu, X., Suarez, G.D., Wang, J., Lis, J.T., Huang, X., Cheung, P.P.H.*, EmPC-Seq: Accurate RNA-sequencing and Bioinformatics Platform to Map RNA Polymerases and Remove Background Error, Bio-Protocol, 11, 4, (2021) [Research Article]

9. Cheung, P.P.H., Jiang, B., Booth, G.T., Chong, T.H., Unartar, I.C., Wang, Y., Suarez, G.D., Wang, J., Lis, J.T., Huang, X., Identifying Transcription Error-Enriched Genomic Loci Using Nuclear Run-On Circular-Sequencing Coupled with Background Error Modeling, Journal of Molecular Biology, S0022-2836(20)30284-9, (2020) [Research Article; Impact Factor: 6.151]

10. Tse, K.M., Xu, J., Xu, L., Sheong, F.K., Wang, S., Chow, H.Y., Gao, X., Li, X., Cheung, P.P.H.*, Wang, D.*, Zhang, Y.*, Huang, X*. Intrinsic cleavage of RNA polymerase II adopts a nucleobase-independent mechanism assisted by transcript phosphate, Nature Catalysis, 2, 228–235 (2019) [Research Article; Impact Factor: 40.706]

11. Cheung, P.P., Rogozin, I.B., Choy, K.T., Ng, H.Y., Peiris, J.S., and Yen, H.L Comparative mutational analyses of influenza A viruses. RNA 21, 36 (2015) [Research Article; Impact Factor: 5.636]

12. Cheung, P.P., Watson, S.J., Choy, K.T., Fun Sia, S., Wong, D.D., Poon, L.L., Kellam, P., Guan, Y., Malik Peiris, J.S., and Yen, H.L. Generation and characterization of influenza A viruses with altered polymerase fidelity. Nature Communications 5, 4794.  (2014) [Research Article; Impact Factor: 17.694]

13. Cheung, P.P., Leung, Y.H., Chow, C.K., Ng, C.F., Tsang, C.L., Wu, Y.O., Ma, S.K., Sia, S.F., Guan, Y., and Peiris, J.S., Identifying the species-origin of faecal droppings used for avian influenza virus surveillance in wild-birds. Journal of Clinical Virology 46, 90,  (2009) [Research Article; Impact Factor: 14.481]