Cancer cells are embedded in a complex microenvironment that includes extracellular matrix and other cell types including endothelial cells, fibroblasts, and immune cells. Our research program exploits bioengineering tools to synthesize tumor microenvironments ex vivo to systematically probe the role of individual cues on cell fate, to interrogate the tumor microenvironment in situ, and to perturb the tumor by delivering therapeutic cargo that penetrates the tumor microenvironment. Some of our recent contributions have been to develop a new class of 'synthetic biomarkers' composed of peptide-decorated nanoparticles to monitor the tumor microenvironment noninvasively in the urine , and the discovery that tumor-penetrating peptides can deliver siRNA into tumors and silence 'undruggable' gene products with therapeutic impact.
Like hepatocytes, the fate of cancer cells is highly dependent on their interactions with the microenvironment. This recognition led us to apply the same technologies developed for dissecting the liver to understand how tumor microenvironments influence disease progression and suggest possible interventions. Paralleling our approach in the liver, we have focused on (i) synthesizing artificial tumor microenvironments, (ii) interrogating in vivo microenvironments with nanoparticle probes, and (iii) perturbing the tumor by delivering therapeutic cargo that penetrates the tumor microenvironment.