Dr Jane Zhou Jie
Assistant Professor 
Department of Microbiology

I did my PhD research in the Department of Microbiology at The University of Hong Kong in 2003-07 under the supervision of Prof Zheng Bojian and Prof Yuen Kwok-yung. After my postdoctoral training at the University of California, San Francisco (UCSF), I joined the department in 2009 as a research assistant professor. During the past two decades, I have focused on the pathogenesis of viral infections, particularly those from emerging respiratory viruses. To explore the host vulnerability to pandemic influenza virus H1N1 and avian influenza virus H7N9, we integrated genome-wide disease association data and gene expression profiles to prioritize candidate genes for functional characterization, and we identified a number of disease-important genes for human influenza, including CD55, Galectin 1, TMPRSS2, GLDC and SPINK6. 

Conventional biomedical research relies upon the use of experimental models such as cell lines and animal models. Human tissue such as the respiratory tract, however, are composed of diversified and specialized cell types. Cell lines and animals are unable to recapitulate the high complexity and specific features of human tissue. Recent advances in stem-cell technology enable the generation of organoids, also known as “mini-organ or organ-in-a-dish”. These are 3D cellular clusters that can faithfully mimic the architecture and functionality of their native organ, thus representing a major breakthrough in human biology.  

Organoids enable scientists to recapitulate and study in vivo biological processes in culture plates, opening a new arena for diverse biomedical and pharmaceutical applications. There are multiple types of organoids in the rapidly growing market, human intestinal organoids and patient-derived cancer organoids account for the biggest proportion. 

Yet, a robust and well-defined respiratory organoid culture system is elusive. The human respiratory epithelium, the primary infection site of respiratory pathogens including SARS-CoV-2, is lined with two distinct types of epithelia, the airway and the alveolar epithelium. Immortalized cell lines such as A549 or Calu3 are commonly utilized to study respiratory biology and pathology. These homogeneous cell lines, however, are unable to simulate the multicellular complexity and functional diversity of human respiratory epithelia, let alone model respiratory infections, including SARS-CoV-2 infection. 

Our team established a two-phase, bipotential organoid culture system that allows scientists to reconstruct and expand the entire human respiratory epithelium in culture plates, which is the first and most advanced respiratory organoid culture system in the world. We derive organoids from primary lung tissues and nasal cells in a highly efficient manner, which provides a stable and self-renewable source for long-term expansion. We induce proximal and distal differentiation in the long-term expandable organoids and generate mature airway and alveolar organoids that morphologically and functionally phenocopy the native human airway and alveolar epithelium.[1] [2] [3] Specifically, We establish a bipotential organoid culture system able to rebuild and expand the entire human respiratory epithelium in vitro with high efficiency and stability. These physiologically-active respiratory organoids are optimal in vitro models for studying respiratory diseases including influenza and COVID-19.

Respiratory organoid culture system established by HKU Microbiology  

In the wake of the COVID-19 outbreak, we demonstrated SARS-CoV-2 replication in human intestinal organoids, suggesting that the human gastrointestinal tract is an alternative viral transmission route. We also developed the first bat intestinal organoid culture. Bat organoids are fully susceptible to SARS-CoV-2, lending support to the proposed bat origin.[4] Importantly, bat organoid opens up a new avenue to isolate and cultivate the previously uncultivable viruses and to assess the zoonotic potential.[5]       

Apart from the vast applications in basic biology and translational research, these world-leading respiratory and intestinal organoids are biologically-relevant tools for recapitulating and evaluating the infectivity of emerging viruses to humans, a longstanding threat to public health worldwide. Nature and a subsidiary journal recently reported our organoid-based virus research, especially my research work on COVID-19.[6] [7] The organoid models established by our team can be extensively utilized in multiple disciplines for studying human biology and pathology beyond our research area of virus-host interaction.


[1] Zhou J, Li C, Sachs N, Chiu MC, Wong BH, Chu H, Poon VK, Wang D, Zhao X, Wen L, Song W, Yuan S, Wong KK, Chan JF, To KK, Chen H, Clevers H, Yuen KY. Differentiated human airway organoids to assess infectivity of emerging influenza virus. Proceedings of the National Academy of Sciences U S A. 2018 Jun 26;115(26):6822-6827.
[2] Chiu MC, Cun Li, Xiaojuan Liu, Yifei Yu, Jingjing Huang, Zhixin Wan, Ding Xiao, Hin Chu, Jian-Piao Cai, Biao Zhou, Ko-Yung Sit, Wing-Kuk Au, Kenneth Kak-Yuen Wong, Gang Li, Jasper Fuk-Woo Chan, Kelvin Kai-Wang To, Zhiwei Chen, Shibo Jiang, Hans Clevers#, Kwok-Yung Yuen#, Zhou J#. 2022. A bipotential organoid model of respiratory epithelium recapitulates high infectivity of SARS-CoV-2 Omicron variant. Cell Discovery. 2022 Jun 17;8(1):57.
[3] Chiu MC, Li C, Liu X, Song W, Wan Z, Yu Y, Huang J, Chu H, Cai J, Kai-Wang To K, Yuen KY, Zhou J#. Human nasal organoids model SARS-CoV-2 upper respiratory infection and recapitulate the differential infectivity of emerging variants. mBio. 2022 Aug 30;13(4):e0194422
  [4] Zhou J#, Li C. Liu X, Chiu MC, Zhao X, Wang D, Wei Y, Lee A, Zhang AJ, Chu H, Cai JP, Yip CC, Chan IHY, Wong KKY, Tsang OTY, Chan KH, Chan JF, To KK, Chen H, Yuen KY#. Infection of bat and human intestinal organoids by SARS-CoV-2. Nature Medicine. 2020 Jul;26(7):1077-1083.  
[5] Liu X, Li C, Wan Z, Chiu MC, Huang J, Yu Y, Cai JP, Chu H, Jiang S, Kwok-Yung Yuen#, Zhou J#. Analogous comparison unravels heightened antiviral defense in bat organoids and boosted viral infection upon immunosuppression. Signal Transduction & Targeted Therapy. 2022 Dec 19;7(1):392.  
[6]Nature. 2021 May;593(7860):492-494. https://www.nature.com/articles/d41586-021-01395-z
[7]Nature Reviews Molecular Cellular Biology. 2020 Jul;21(7):355-356. https://www.nature.com/articles/s41580-020-0258-4