May 2023 - Aug 2024

May 2023 - Aug 2024
Supervisor: Prof. Mohit Kumar Jolly

Cancer progression is a multifaceted process and tumour cells undergo a series of changes that facilitate their survival, proliferation and migration to various sites in the body. Phenotypic plasticity, epitomized by the Epithelial-Mesenchymal Transition (EMT), is a cornerstone of cancer metastasis. While bidirectional associations such as EMT–drug resistance (Sahoo et al. 2021), EMT–stemness (MK Jolly et al. 2015), EMT–Immune Suppression (Sahoo et al. 2021), and EMT–metabolism (Galbraith et al. 2023) have been reported, studies addressing multiple axes simultaneously remain limited and thereby, investigating this interconnected network is of crucial importance and can aid in developing new combinatorial therapies to combat cancer.

I constructed a minimal gene regulatory network by identifying modules consisting of key genes associated with different axes of phenotypic plasticity. The proposed gene regulatory network was simulated using continuous (RACIPE) and discrete (Boolean) simulations to study the emergent phenotypic states due to the intra- and inter-module interactions. The simulations revealed the existence of two mutually repressing and self-activating “teams”, one consisting of genes that promote EMT and another consisting of genes that have an inhibitory effect on EMT.

This work is now out on bioRxiv as a pre-print: Read it by clicking here.