Stress-driven stromal transcriptional reprogramming

Stress responses are evolutionarily conserved survival mechanisms that are fundamental to normal physiology. In cancer, these pathways are subverted to support the growing tumor. We hypothesize that microenvironmental pressures such as hypoxia, oxidative stress, and protein misfolding reshape the transcriptional states ofmalignant and non-malignant cells in the tumor, in a coordinated manner. By understanding, and eventually targeting specific stress pathways in the tumor microenvironment, we aim to induce transcriptional remodeling that will shift the non malignant cells to a less pro-tumorigenic and more homeostatic phenotype, creating a potential therapeutic point of intervention.