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. |