Research Projects

Epithelial to Mesenchymal Transition (EMT) is a crucial cellular program involved in development, wound healing, and cancer metastasis. Transforming Growth Factor-β (TGF-β) is a potent inducer of EMT, regulating this program through a TGF-β receptor-SMAD mediated pathway. TGF-β induces EMT by regulating several interlinked feedback loops involved in the EMT regulatory network. Experimental and theoretical studies have shown that TGF-β-induced EMT occurs in a switch-like manner, regulating cell cycle-inducing and inhibitory genes and controlling cellular proliferation in a context-dependent manner. How TGF-β simultaneously controls the cell cycle and EMT dynamics by controlling these cross-talk regulations between them remains poorly understood. The project aims to decipher how TGF-β signalling governs the cross-talk regulation between cell cycle and EMT dynamics in a dose-dependent manner and unravel the key cell cycle or EMT components that orchestrate this cross-talk regulation. The hypothesis is that it will be possible to modulate the EMT propensity of cancerous cells by identifying and appropriately modulating the key cross-talk regulators of EMT and cell cycle under the influence of TGF-β. Live-cell imaging studies will be performed to quantify EMT propensity and cell cycle period and phase duration distributions in a dose-dependent manner. An experimental data-driven comprehensive mathematical model of TGF-β-mediated cell cycle and EMT dynamics will be constructed to predict the key regulators of the cross-talk between the cell cycle and EMT. This will enable the design of novel therapeutic strategies to resist EMT in cancer cells.