Project summary/Abstract
Profiling fatty acid uptake and activity in single tumor cells (PIs: Min Xue, UC Riverside; Wei Wei, UCLA)
Altered fatty acid metabolism is involved in many types of diseases, as exemplified in cancer. Many cancer
cells exhibit elevated fatty acid uptake and metabolic activity. In these cells, fatty acids can be used as
alternative energy fuels or biomass building blocks to support the uncontrolled growth, defend stress and
promote metastasis. Because cancer cells are extremely heterogeneous, their activities on fatty acid uptake
and metabolism are expected to vary significantly even within the same tumor sample. Similar to the
heterogeneity involving other metabolic and signaling pathways, the variation in fatty acid metabolism also
contribute to the cell plasticity. This variation helps cancer cells adapt to nutritional, environmental and
therapeutic stress, and facilitates the development of drug resistance and metastatic lesions. Therefore, the
ability to analyze cellular fatty acid metabolism, especially at single cell level, promises more insights to cancer
biology. In this proposal, we aim to develop a surface-based chemical method for quantifying fatty acid uptake
as well as its metabolic activities in single cells. We will first synthesize a panel of fatty acid analogs, and use
cell uptake experiments to validate their utility as probes for assessing cellular fatty acid uptake and its related
metabolic activities. We will employ surface-based detection schemes to quantify the selected probes.
Subsequently, we seek to incorporate this detection method into a well-established microfluidics-based single
cell analytical platform. Successful implementation of the proposed work will provide a tool for analyzing fatty
acid uptake and metabolic activity at single cell resolution. In addition, we will be able to perform multiplexed
analysis to study the interplay between fatty acid metabolism and other metabolic and oncogenic signaling
pathways, which may provide therapeutic implications that cannot be easily revealed by bulk-level analysis.