2017-02-13
Cell signaling is important for many physiological and pathological processes. Although most signaling pathways have be extensively studied, how molecules from different pathways crosstalk with each other remain elusive. We therefore use systems biology to address this question in a stepwise manner:
(1) Focused approach: Fluorescence live-cell imaging and automated quantitative approaches were recruited, to elucidate how Ca2+ was temporally & spatially controlled to exert local & global effects on cell motility & polarity.
(2) Interactive approach: We examined how Ca2+ homeostasis interacts with cell adhesion machinery to regulate cell movement in angiogenesis and cancer metastasis, using mathematical modeling and biological experiments.
(3) High-throughput approach: Hypothesis-driven shRNA screens were conducted to understand interactions between fibroblast growth factor receptors (FGFRs) and interactions between signaling pathways, in endothelial & cancer cell migration.
(4) Big-data approach: We explored fatal cardiac arrhythmia through next-generation sequencing and identified a potential K+-Ca2+ interactions for proper cardiac electrical activities. Mechanistic investigation is under the way.
Altogether these approaches will provide us with a comprehensive view how signaling interactions contribute to physiology and diseases.