Claudia Fischbach, Project Leader
Triple negative breast cancer (TNBC) and obesity lead to physical changes in the microenvironment, including aberrant multiscale structure and mechanics of the extracellular matrix, disturbed distributions of soluble factors, and population-level abnormalities in collective cell behavior. However, the functional interconnections between these physical variations and tumor metabolism remain unclear. This gap in understanding can be attributed to a lack of computational and experimental models that permit reliable prediction, recapitulation, and study of tumor and obesity-associated physical mechanisms in TNBC. By integrating biomaterials, tissue engineering, microfabrication, and computational models, Project 1 will investigate the hypothesis that physical changes in the microenvironment regulate malignancy by perturbing cellular metabolism. Furthermore, we will test whether obesity primes for tumorigenesis through similar mechanisms. To address these hypotheses, engineering-centric approaches will be integrated with transgenic mouse models, patient-derives xenografts, patient-derived organoid cultures, and drug testing. This approach will reveal novel mechanisms in tumor metabolic reprogramming for clinical translation.