The Contag laboratory develops macroscopic and microscopic optical imaging tools and uses imaging to assess tissue responses to stress, reveal immune cell migration patterns, understand stem cell biology and advance biological therapies. The research mission of the Contag laboratory is to develop and use noninvasive imaging tools that can simultaneously reveal the nuances of biological processes and provide an overall picture of disease states for the purpose of developing and refining novel interventions. These tools are being applied to examine the close relationships between cancer and the immune system. Chronic inflammation often precedes progression to cancer, and this suggests that signals from immune cells may initiate, drive, and/or maintain a predisposition to cancer and mediate its progression. Identifying the molecular mediators of the changes that precede progression to cancer in otherwise histologically normal cells and tissues would lead to new therapeutic targets that would enable disease prevention in high-risk populations including relapse from treated cancers. Among the various signals produced by immune cells, extracellular vesicles are the most complex, and perhaps the most nonspecific, implicating them in the disease process. We are examining the role of extracellular vesicles from activated immune cells, and cancer cells, in creating premalignant fields, and characterizing the molecular signals that precondition normal tissues and drive malignant transformation. Uncovering the molecular mechanisms of premalignancy and the signals that convert these cells to cancer lies at the foundation of cancer biology and will impact the diagnosis, treatment and management of all cancers. In addition, since the imaging tools we develop are sensitive and image over a range of scales from micro- to macroscopic, and are well-suited for the in vivo study of cellular and molecular biology, we are developing, and using, advanced microscopic tools with the aims of detecting and studying cancer at high resolution in vivo. These approaches use micro-optics to develop miniaturized confocal microscopes and Raman endoscopes that can reach inside the human body to interrogate disease states. This is enabling point-of-care microscopy that is changing the diagnostic paradigm from biopsy and histopathology to in vivo pathology. The opportunity to study tumor margins with arrays of microscopes will enable improved tumor detection and guided resections.