Novel experimental platform of human respiratory tract for emerging infectious diseases and precision medicine:

For understanding pathogenesis, for therapeutic screening and precision medicine

Acute lung injury and Acute Respiratory Distress Syndrome (ARDS) are major causes of morbidity and mortality worldwide. Diverse causes lead to this pathology, including severe viral infections (avian influenza H5N1; SARS; MERS) and bacterial sepsis.

 

Host responses such as innate immune dysregulation and resulting impaired alveolar fluid clearance contribute to the pathology; thus therapeutic strategies that target these adverse host responses need to be developed for use in conjunction with antimicrobials.

 

This program aims to improve the treatment of acute lung injury by a) Producing innovative physiologically relevant disease platforms for screening therapeutic candidates and b) Developing molecules for treating acute lung injury. This will be achieved in four interconnected and synergistic projects that also synergize with the other research programs of I2PM.

KEY PROJECTS

  1. Develop acute lung-injury screening platforms for identification of novel therapeutic targets and for screening of potential interventions;
     

  2. Identify the biological proteins and / or micro-vesicles produced by Mesenchymal Stromal Cells (MSC) that reverse acute lung injury. This is based on our previous work showing that treatment with mesenchymal stromal cell (MSC) improves alveolar fluid clearance and up-regulates the sodium and chloride transporters in models of acute lung injury;
     

  3. Evaluate the use of novel synthetic ion channel compounds to treat acute lung injury. We have already demonstrated the feasibility of this approach. We will screen further novel synthetic compounds. Lead compounds will be evaluated in pre-clinical models;
     

  4. Develop a novel “mini” 3D human respiratory system and “lung-on-a-chip” model for assessment of pathogenesis and drug screening for respiratory diseases.  A biobank of ready-to-use experimental human airway and nasopharyngeal organoids will be generated to assess the susceptibility of the human lung to different viruses and to investigate host genetic factors associated with adverse outcome. Project 4 will synergize with projects 1-3 above and with Research Program 1 HHGP, to develop precision medicine. The screening platforms will become a service marketed to the pharmaceutical sector.

DELIVRABLES

  1. Novel therapeutics for acute lung injury;
     

  2. Novel, physiologically relevant experimental models of the human respiratory system for drug development;
     

  3. Creation of intellectual property and technology-based startups for commercialization and translation into global healthcare solutions.

KEY RESEARCH STAFF IN THE TEAM

We have a multidisciplinary team with proven track-record of working together with previous joint publications. 

Malik PeirisMichael CW Chan and Kenrie PY Hui (virologists), John M Nicholls (pathologist) and George Tsao (all from HKU) have been working together on pathogenesis of virus respiratory infections and experimental models of the human respiratory system for over 10 years. 

Roberto Bruzzone (HKU-PRP) studies host-pathogen interactions. 

Michael Matthay and Jae W Lee (UCSF) are world leaders in the pathogenesis and therapy of acute lung injury and ARDS and have joint publications with the HKU group. 

Samy Gobaa (IP) is an expert in microfluidics who will help generate a microfluidic perfusion on a chip to mimic physical stimuli in the respiratory system.

THE TEAM

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Michael Chan

Principal Investigator 

Dr. Michael Chan received his PhD degree in Medical Science from the Chinese University of Hong Kong, followed by the post-doctoral fellowships in influenza virus and infectious diseases at the University of Hong Kong in 2004.

 

Dr. Chan’s main research interests are the virus-host interaction and pathogenesis of influenza virus and coronavirus (SARS-CoV-2, SARS-CoV and MERS-CoV) using ex vivo human respiratory explant cultures and in vitro well-differentiated human respiratory epithelial cells. Major focuses of his current work are: (1) Risk assessment of influenza virus and coronavirus using ex vivo explants and in vitro respiratory epithelial cells model. (2) Mechanism of lung injury upon severe influenza virus and coronavirus infection (3) Human nasal, nasopharyngeal, airway and distal lung organoids development and risk assessment for emerging infectious diseases (4) Role of human distal airway stem cells in respiratory epithelium regeneration upon influenza H5N1 virus, SARS-CoV-2, MERS-CoV and SARS-CoV infection. (5) Role of mesenchymal stromal cells and exosomes/microvesicles in reverse influenza H5N1 associated acute lung injury (6) Novel therapeutic options for severe human influenza virus and coronavirus infection

Publications 
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