Research Projects

Therapeutic resistance in breast cancer has been a significant challenge for decades, influenced by factors such as epithelial to mesenchymal transition (EMT), drug efflux pump genes, detoxification genes, quiescence, and evasion of apoptosis. This proposal aims to address drug resistance by modulating the Extracellular Matrix (ECM) genes of cancer cells using epigenetic regulators. The hypothesis is that the membrane rigidity of cancer cells, a major hurdle towards drug penetration, can be modulated by epigenetic regulators for better drug uptake and sensitizing drug-resistant relapse-prone Triple Negative Breast Cancer (TNBC). The main experiments will involve culture of MDA-MB-231 and MDA-MB-468 cells in isolation or presence of HFF, as well as phenotypic assays to score for alteration in drug uptake by genetically engineered cancer cells. Immunofluorescence will be used to quantify the expression of different ECM proteins under resistant conditions. Biochemical, biophysical, cell biological, genomic, metabolic pathway analysis, and proteome and post-translational modifications of proteins will be used to understand the role of chromatin readers in ECM remodelling. The project aims to understand the role of epigenetic regulators in sensitizing cancer cells for better drug uptake and potentially uncover new mechanisms of alteration of cellular matrix stiffness leading to drug resistance. The use of Plant Homeodomain (PHD) finger proteins from an epigenetic perspective could help regulate this phenomenon.