Core area of research: Tumour microenvironment, 3D models, spheroids, tumour immunology.

My primary research interest is centered on utilizing various 3D cell culture models, such as organoids and spheroids derived from patient tumour samples or cancer cell lines. The 3D structures generated from patient tumours closely resemble the original tumor, and these organoids generated from patient tissue can be cryopreserved in a biobank. These organoids have significant potential for predicting individual patient responses to chemotherapy. A key focus of my research involves examining the interactions between PAK1 (p21-activated kinase) inhibitors and Tyrosine Kinase Inhibitors (TKIs) in lung cancer cell lines and spheroid models, to clarify the mechanisms by which these inhibitors impact essential signalling pathways.

 

Resistance mechanisms to gefitinib and combination approaches with new therapies for lung cancer 

Gefitinib, a tyrosine kinase inhibitor approved for lung cancer, targets EGFR but often faces resistance due to compensatory pathways like PAK1 activation. This project evaluates novel PAK1 inhibitors for their ability to counter gefitinib resistance, with animal studies underway for validation. We are also systematically investigating the synergy between PAK1 inhibitors and gefitinib. These inhibitors may enhance the effectiveness of TKIs in lung cancer by overcoming resistance. To understand this effect, we use EGFR mutant and wild-type lung cancer cell line models. 

 

Exploring 3D spheroids/organoids as pre-clinical tools in Cancer Research 

My research is centered on generating spheroids from cell lines – sophisticated three-dimensional models developed in the laboratory to replicate natural 3D architecture. These models serve as robust platforms for preclinical testing and facilitate the study of cell-cell interactions. 

A key component of my work involves the development and application of organoids derived from patient tumour samples. These organoids are particularly valuable because they closely emulate the native tumour microenvironment, offering an accurate depiction of complex tissue architecture observed in vivo. This high level of fidelity to original tumour structures underpins my commitment to advancing organoid systems as preclinical models, which prove crucial for drug screening and for deepening our understanding of tumour microenvironment dynamics. 

To address technical limitations often encountered in organoid research—including challenges related to light scattering and restricted imaging depth—we utilise state-of-the-art technologies such as the Leica 3D Thunder live cell imaging system. This enables enhanced visualization and monitoring of organoid structures, thereby supporting precise evaluation of their progression and interactions.