Mammalian biology occurs in complex environments of living tissues and complex organ structures where there is potential for rapid change. To study the dynamics of biological processes, therefore, we use noninvasive approaches that have cellular resolution and molecular specificity, and that can reveal dynamic changes as they occur in the living body. We have developed imaging approaches based on optical reporter genes and have used them to reveal immune cell trafficking patterns, regulation of gene expression, extent of tumor growth and nature of host responses to infection. Our initial experimental approach was based on the observation that light can pass through mammalian tissues, much the same as when light from a flashlight is shined through one's hand in a dark room. The source of light in our approach is internal; that is, we use genes originating from fireflies and other "glow-in-the-dark" (bioluminescent) organisms to mark mammalian cells and pathogens. These labeled entities are then used in animal models of human biology and disease, and the light that they produce is externally monitored to reveal levels of expression, growth rate, or movement within tissue and organs. The strength of this method is that it can be used to simultaneously reveal the nuances of biological processes, and the overall biological response in living animals. Recently, we have revealed the kinetics of stem cell engraftment and hematopoietic reconstitution, elucidated the nature of minimal residual disease states following cancer therapy and identified tissue sites that pathogens use to evade the host immune response. Optical methods of molecular imaging are extremely powerful in preclinical models and have tremendous potential, but a wide range of tools is becoming available for studying biology in vivo. We therefore use many of these tools and approach biological questions with multimodality strategies. The focus of our efforts is the cells and molecules that control the body’s response to insult and enable regeneration of damaged tissues and organs.

• Wender PA, Goun EA, Jones LR, Pillow TH, Rothbard JB, Shinde R, Contag CH "Real-time analysis of uptake and bioactivatable cleavage of luciferin-transporter conjugates in transgenic reporter mice." Proc Natl Acad Sci U S A 2007; 104: 25: 10340-5 More
• Thorne SH, Negrin RS, Contag CH "Synergistic antitumor effects of immune cell-viral biotherapy." Science 2006; 311: 5768: 1780-4 More
• Hardy J, Francis KP, DeBoer M, Chu P, Gibbs K, Contag CH "Extracellular replication of Listeria monocytogenes in the murine gall bladder." Science 2004; 303: 5659: 851-3 More
• Cao YA, Wagers AJ, Beilhack A, Dusich J, Bachmann MH, Negrin RS, Weissman IL, Contag CH "Shifting foci of hematopoiesis during reconstitution from single stem cells." Proc Natl Acad Sci U S A 2004; 101: 1: 221-6 More
• Shachaf CM, Kopelman AM, Arvanitis C, Karlsson A, Beer S, Mandl S, Bachmann MH, Borowsky AD, Ruebner B, Cardiff RD, Yang Q, Bishop JM, Contag CH, Felsher DW "MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer." Nature 2004; 431: 7012: 1112-7 More