Feature Story Research & Innovation
Research Grants Council’s Theme-based Research Scheme (TRS) 2021/22
Project Title
Ecology, molecular virology and pathogenesis of SARS-CoV-2: From bedside to bench and back
Project Coordinator
Prof. Dong-Yan Jin
Project Description
On the basis of our study and discoveries of coronaviruses (CoVs) in the past 18 years, multidisciplinary research in this project will be carried out in three intertwined areas to address key scientific questions surrounding ecology, molecular virology and pathogenesis of SARS-CoV-2, thereby paving the avenue to conceptually new approaches for early diagnosis, prevention and treatment of COVID-19, essential to bringing an end to the pandemic. First, we will derive new insights into the origin and evolution of SARS-CoV-2 by analyzing one of the world’s largest collection of samples from bats and other animals. Concurrently, we will continue to discover emerging variants of SARS-CoV-2 with altered pathogenicity and transmissibility. We will also define the mechanism of asymptomatic SARS-CoV-2 infection in bats and humans. This will provide the materials and basis for the next part of our project. Second, we will unravel new mechanism of SARS-CoV-2 entry and replication. We will also characterize the roles of several lineage-specific accessory proteins in SARS-CoV-2 biology and pathogenesis. Forward genetic screens based on RNAi and CRISPR technology will be performed to identify novel host dependency and restriction factors. Finally, we will pursue translational research to revolutionize diagnosis, vaccine development and treatment of COVID-19. Concepts established in our project will be harnessed to design and develop new strategies, methods and leads for early and rapid diagnosis, immunization with live attenuated and synthetic vaccines, as well as therapeutic treatment targeting either the virus or the host.
Research Grants Council’s Research Fellow Scheme (RFS) 2021/22 Project Title An immune perspective on exploiting stemness as a cancer cell vulnerability for the treatment of liver cancer
Project Coordinator
Dr. Stephanie Ma
Project Description
Hepatocellular Carcinoma (HCC) is a particularly prevalent and deadly disease in Hong Kong and China. Despite improvements in the outcome of patients with HCC, the overall prognosis of this cancer is still unsatisfactory because of late presentation, drug resistance and frequent tumor recurrence. PD-1 blockade represents a major therapeutic avenue in anti-HCC immunotherapy; but there remain serious limitations including the accurate assessment and prediction of tumor response and overcoming the immunosuppressive effects of the tumor microenvironment. Cancer stemness is a property that is now widely accepted to be associated with drug resistance, tumor relapse and the general unfavorable outcome of HCC. The enhanced ability of cancer stem cells (CSCs) to give rise to new tumors suggests that these cells likely have an advantage in evading immune detection and elimination. Our pilot data suggests that activation of a stemness program in HCC appears to limit anti-tumor immune responses. We propose a project on liver CSC immunology that will encompass looking at cancer stemness and their connection with A-to-I RNA editing, mutation-driven pathway activation and immune evasion. Findings of this project will also aid to improve patient stratification for immuno-oncology therapy.
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