Principal Investigator Ralph Weissleder
New ultra-resolution microscopic imaging technologies are being used to understand the complexity, heterogeneity and in vivo behavior of cancers. During cancer development we are interested in understanding the spatiotemporal activity of specific proteins (certain kinases and receptors), biological processes (apoptosis, proliferation) and cell-cell interactions in vivo.
Equally important, we are also interested in trying to understand why so many cancer drugs fail. Using companion imaging drugs (see next section), we determine how individual cancer cells in tumors respond to therapy in vivo by measuring both the uptake and distribution of drugs in tumor cells (pharmaco-kinetics, PK), as well as the multiple downstream responses that play out over different time-scales (pharmaco-dynamics, PD). These single cell “systems pharmacology” experiments invariably use engineered cell lines, mouse models using a panoply of fluorescent reporter proteins and fluorescently labeled drugs. Results from ongoing projects will likely have an impact on our understanding of tumor biology at the systems level, promote earlier clinical diagnosis and accelerate drug development.