Research Projects
Diagnostic and Therapeutic Biomarkers in Lung Cancer

Lung cancer cell lines and immortalised bronchial epithelial cell lines are being established from local patients. These local cell lines were derived from different histological subtypes of tumours including adenocarcinoma, squamous cell carcinoma and malignant pleural mesothelioma. They all bear the common repertoire of oncogenic/therapeutic targets (EGFR mutation, ALK translocation, PD-L1 expression) in local patients with lung cancer or airway disorders. Through the characterisation of these cells with genome-wide expression profiling, whole-exome sequencing and tumorigenicity in immune-compromised mice, new biomarkers and the oncogenic pathways they adopt are being studied. Oncogenes like EGFR are being transferred or knocked down and their relation to putative tumour suppressor genes like LATS2 or in relation to expression of nAChR to study the impacts of such manipulation on lung tumour transformation.

Newer methods of organoid culture and co-culture with immune cells are being adopted. These newer cell culture methods generate lung cancer organoids that provide good platforms for therapeutic drug or siRNA screenings to find the relevant critical vulnerabilities or targets for therapy.

Genome-wide information in mRNA expression, copy number variation, DNA methylation, proteomics, and whole exome mutation analyses of these lung cancer cell lines or organoids are integrated to identify molecular biomarkers predictive of response to clinically available drugs. This provides a preclinical platform for developing and testing new lung cancer therapies and also could be a method for developing cellular or circulating biomarkers that can be used in clinical trials.

Acquired resistance to chemo- or targeted therapies poses a major challenge for the treatment of lung cancer with disease progression. The role of circulating biomarkers in detection of early relapse is being studied. Cell line/organoid models of acquired resistance have been established and the cellular mediation of resistance via extracellular vesicles or exosomal message transfer is being studied. These extracellular vesicle transfer could also be used to study the mediation of metastasis in lung cancer.

Example projects:

1. Transfer of extracellular vesicles in modulation of drug resistance or sensitivity
2. The role of nicotinic acetylcholine receptor in lung carcinogenesis
3. The effects of LATS2 on chemo-sensitivity in advanced stage lung cancer
4. Circulating tumour DNA in early detection of lung cancer
5. Biomarkers for lung cancer screening that may improve screen detection rate

Professor DCL Lam, Department of Medicine

The aim of my research laboratory is to develop and implement new ways to improve the prevention, early detection, diagnosis and treatment of lung cancer through multi-disciplinary research that translates results between the laboratory and the clinic.

The research includes components of basic laboratory research, preclinical studies, clinical research including exploration for new drug targets and biomarkers for early detection and screening of lung cancer.  With the strength of different lung cancer cell lines/organoids as mentioned above, new projects could be proposed with selection of different cell line models to answer research questions in different perspectives.

Biography
dcllam@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.