We propose to develop an integrated microchip platform for rapid, reliable and comprehensive diagnosis of cancer by examining the pathophysiological mechanism of tumor-immune interaction. This will be done at both molecular and cellular level. By applying this platform to analyze a large number of clinical samples, we expect to gain new insights about cancer immunobiology that point to new approaches for cancer prevention and treatment. During the K99 phase, I have demonstrated an Integrated barcode platform that can measure a large number of protein markers from small quantities of whole blood or from single cells. A panel of signaling proteins that have important implication in tumor inflammation has been integrated Into the microchip platform. In the ROO phase, I will further utilize this technology to Investigate the fundamental biology of tumor-immune interaction via measuring the paracrine signaling pathways between tumor and immune cells. I will also study the heterogeneity of tumor microenvironment by combining population dynamics modeling and the microchip-based molecular analysis. Once this model is trained with experimental or clinical data, it will become a useful tool to predict the outcomes or therapeutic responses of cancer patients. In addition, an on-chip culture of tumor cells and immune cells will be developed to emulate tumor microenvironment and then used for rapid, effective anti-cancer drug screening. To accomplish these goals, I will (1) use the Integrated barcode chip platform to study chronic Inflammation as a common mechanism in various human diseases and to reveal their correlations; (2) apply this tool to monitor the Immunological responses of cancer treatment; and (3) design a Tumor-on-a-Chip to re-engineer the tumorimmune Interactions ex vivo and use this platform for effective anti-cancer drug screening with rich feedback. |