Specific research questions in the FCT Lab:

1. Synthetic dysmobility

    It is interesting how different signalling pathways coordinate with each other to establish distinct cell migration modules including polarity, motility, cell-matrix adhesion, and cell-cell coordination. To address this question, we conducted a “synthetic dysmobility” cell migration screen by doubly hitting human umbilical vein endothelial cells (HUVECs) with an shRNA and a small molecule inhibitor targeting different pathways.  Then collective cell migration assays were utilized to identify synergistic or antagonistic interactions between these two hits. Candidate interaction pairs were further verified in different cancer cell lines. Single-cell tracing was also employed to elucidate how cell migration patterns of speed, directionality, persistence , and coordination were altered in these interaction pairs. With clear understanding of synthetic signalling interactions, we will develop novel therapeutic strategies against cell migration-related disease processes including angiogenesis, wound healing & cancer metastasis.

2. Calcium-adhesion interactions in cancer

    Aberrant calcium signaling is critical in cancer development, but how calcium regulates cancer cell migration has remained elusive, with contradictory reports showing that calcium may help or stop tumor progression in different cancers. Our recent explorations indicated the fact that calcium enhanced cell-matrix adhesion might be beneficial or detrimental to cancer cell migration depending on its basal adhesion status. We are currently investigating its molecular mechanism by monitoring focal adhesion (FA) dynamics in high-resolution live-cell imaging. Our ultimate goal is to develop personalized anti-cancer treatment based on basal calcium signaling and adhesion strength of the tumor cells.

 3. Physical interaction of FGFRs with other RTKs

  Fibroblast growth factor receptor (FGFR) signalling is involved in epithelial-mesenchymal transition (EMT) and cell migration. Active FGFR mutations have also been reported in diseases including cancers. However, although potent FGFR inhibitors are available, their therapeutic effects are variable. We therefore investigate the functional significance of FGFR signalling in diseases. Using cancer and thyroid eye disease as models, we specifically focus on interactions between FGFRs and other receptor tyrosine kinases including epidermal growth factor receptor (EGFR) and transforming growth factor beta receptor (TGFbR). In contrast to the classical scheme of signalling interaction, physical presence of FGFR rather than its kinase activity seems to be critical for FGFR interactions with other RTKs. Such a novel mode of receptor interaction may lead to paradigm shifts of targeted therapies in cancers and in inflammatory disorders.

4. Spatial & temporal regulation of Calcium in physiological & pathological conditions

With recent advance of fluorescent live-cell calcium indicators, intracellular changes of local and global calcium signals can be visualized in real-time manners. One of our talented Ph.D. students Yu-Chiao Lin has accordingly established a live-cell calcium imaging platform, with cells steadily expressing genetically-encoded calcium indicators (GECI) in different intracellular compartments including cytosol, endoplasmic reticulum (ER) & mitochondria. Using this platform we are investigating dynamic calcium interchange between ER and mitochondria. We are also exploring the functional significance of aberrant calcium signals in liver cancer & fatal cardiac arrhythmia, with the hope to develop novel treatments in those severe diseases.