Point-of-care optical spectroscopy platform and novel ratio-metric algorithms for rapid and systematic functional characterization of biological models in vivo

项目总结

PROJECT SUMMARY Cellular metabolism is highly dynamic and strongly influenced by its local vascular microenvironment, gaining a systems-level view of tumor metabolism and vasculature in vivo is essential in understanding many critical cancer biology questions. However, there are surprisingly few techniques available that can quantify the key metabolic and vascular endpoints together in vivo with easy access. The goal here is to fill this gap by developing a point-of-care optical spectroscopy platform with a tumor-sensitive fiber probe and novel ratio- metric data processing techniques to quantify the major axes of tumor metabolism (glucose uptake, mitochondrial membrane potential, Bodipy) and the associated vasculature (oxygenation, hemoglobin) on biological models in vivo. For scientific validation and translational purposes, we will compare our techniques with existing metabolic tools, we will also integrate our optical strategies with the state-of-art metabolomics technique, i.e. Stable Isotope-Resolved Metabolomics (SIRM), to provide a rapid and comprehensive understanding in tumor metabolism. We will then demonstrate our synergistic approach through addressing a contemporary problem in cancer therapy for head and neck squamous cell cancer (HNSCC). Specifically, we will address the critical challenge of radio-resistance (RR) in HNSCC and test the hypothesis that radiotherapy (RT) induced HIF-1α and HIF-2α activation and the following metabolic changes are responsible for HNSCC RR and recurrence, the tumor-specific in vivo genetic editing platform targeting on HIF-1α and HIF-2α can improve RT efficacy. Our point-of-care optical spectroscopy along with novel ratio-metric algorithms make our technologies easy to access, easy to use, and systematic, which are all critical to maximizing its accessibility for cancer research. Our spectroscopy techniques and their integration with the SIRM will provide new ways of studying cancer biology and diseases, and they will also impact the study of a wide array of other biomedical problems through the lens of tumor bioenergetics and vasculature. Our study on HNSCC RR mechanisms and the demonstration of tumor-specific genetic editing platform in orthotropic HNSCC models will offer new ways for targeted RT to improve HNSCC patient survival rates. The platforms and methodologies developed in this project will be applicable to the study of RR and recurrence in other types of human cancers.