Diagnostic and therapeutic biomarkers in lung cancer

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.

Current areas of research interest include:
Lung cancer cell lines and immortalized bronchial epithelial cell lines are being established from local patients. These local cell lines were derived from different histological subtypes of tumors 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 characterization 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 tumor suppressor genes like LATS2 or in relation to expression of nAChR to study the impacts of such manipulation on lung tumor transformation.

Newer methods of organoid culture and co-culture with immune cells are bing 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.

Examples of current research project are:
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 tumor DNA in early detection of lung cancer
5. Biomarkers for lung cancer screening that may improve screen detection rate.

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.

Faculty information, funding opportunities and application deadlines: https://www.findaphd.com/phds/program/biomedical-research-hku-li-ka-shing-faculty-of-medicine/?i586p4119