Research Projects
An Immune Perspective on Exploiting Stemness as a Cancer Cell Vulnerability for the Treatment of Liver Cancer

Liver cancer (Hepatocellular Carcinoma, HCC) is a particularly prevalent and deadly disease in Hong Kong and China. Despite definite 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 tumour recurrence. Knowledge of the molecular/cellular targets and mechanisms underlying the development and progression of HCC is of importance as this can provide novel opportunities for therapeutic interventions. Cancer immunotherapy is revolutionising the clinical management of a variety of cancers including HCC. PD-1 blockade represents a major therapeutic avenue in anti-HCC immunotherapy, but there remain serious limitations including the accurate assessment and prediction of tumour response and overcoming the immunosuppressive effects of the tumour microenvironment. Currently, the clinical efficacy of PD-1 pathway inhibition as monotherapy is limited to subsets of HCC patients, with an overall response rate of less than 20%. In particular, HCC is well-known to be accompanied by an immunotolerant microenvironment for the resistance of immunotherapies, where a broad spectrum of immunosuppressive cells is recruited to affect the efficacies of immunotherapies. Cancer stemness is a property that is now widely accepted to be associated with drug resistance, tumour relapse, and the general unfavourable outcome of HCC. Indeed, there is now ample evidence to show that HCC tumour growth is also fueled by stem-like cells within the tumour called cancer stem cells (CSCs) that act very much like the root of the disease. In the past decade, CSC biology and tumour immunology have both separately shaped our understanding of HCC tumorigenesis. However, integrative scientific insights from these two areas have been limited. The enhanced ability of CSCs to give rise to new tumours suggests that these cells likely have an advantage in evading immune detection and elimination. And indeed, there is now emerging evidence to show the roles of major immune cells in promoting CSC expansion, CSC-specific avoidance of immune cell detection and destruction, as well as the ability of CSCs to elicit pro-tumorigenic immune cell activities. But despite this, knowledge regarding the interplay between CSCs and the immune system remains scarce, with studies in HCC particularly limited. 

This will be a basic and pre-clinical study on delineating the complexity of HCC stemness and immune interactions. We aim to functionally, mechanistically, and therapeutically examine the link between cancer stemness, immune tumour microenvironment, and immuno-oncology response in HCC using a combination of molecular, cellular, disease modelling, multiplexed immunohistochemistry, flow cytometry, as well as next-generation sequencing genomic approaches. We believe the new knowledge gained will not only improve our basic understanding of liver CSC biology but also define new opportunities for innovative treatments of HCC targeted at the important liver CSC subpopulation by modulating the surrounding immune microenvironment. Findings will also aid to improve patient stratification for immuno-oncology therapy. 

Multiple MPhil and PhD student positions are currently available.

Prof SKY Ma, School of Biomedical Sciences

Professor Stephanie Ma's research group in the School of Biomedical Sciences, Li Ka Shing Faculty of Medicine at the University of Hong Kong has a long-standing interest in identifying novel stemness vulnerabilities in cancer using the Asian prevalent cancer type hepatocellular carcinoma (HCC) as a model system. We believe that targeting cancer stem cells is a new venture for precision medicine in oncology. Our current goals are to establish new molecular signatures and markers for predicting the occurrence, recurrence, and drug resistance, to improve patient stratification, and identify actionable targets directed at cancer stemness for precision medicine.

Biography
Laboratory Homepage
stefma@hku.hk

For more information or to express interest for this project, please email the supervisor or the specified contact point in the project description.  Interested candidates are advised to enclose with your email:

1. your CV,
2. a brief description of your research interest and experience, and
3. two reference letters (not required for HKUMed UG students seeking MRes[Med]/URIS projects).

Information on the research programme, funding support and admission documentations could be referenced online at the Research Postgraduate Admissions website. General admission enquiries should be directed to rpgmed@hku.hk.

HKUMed MBBS students interested in the Master of Research in Medicine (MRes[Med]) programme may visit the programme website for more information.  

HKUMed UG students interested in the Undergraduate Research Internship Scheme (URIS) may visit the scheme’s website for more information.