Discovery of new biology through label-free imaging
Compared to the labelling approaches, a key advantage of label-free spectroscopic imaging lies in its discovery potential through study of human patient specimens at single cell level. The Cheng group has been shedding new light on cell biology using the advanced spectroscopic imaging tools developed in the lab. As a recent example (Cell Metabolism 2014, 18: 393), by close examination of the fingerprint profile of individual droplets, Cheng and coworkers discovered an unexpected, yet aberrant, storage of cholesteryl ester in human prostate cancer. In the same work, Cheng and coworkers further studied the underlying biology and identified a new target, an enzyme for cholesterol esterification, for treating late-stage prostate cancer by inhibition of cholesterol esterification. In 2015, Cheng and Junjie Li co-founded Resarci Therapeutics LLC, which aims to convert the discovered metabolic signatures (e.g., cholesterol esterification) into cancer treatments via repurposing existing drugs.
In a more recent study (Cell Metabolism, under review) in collaboration with Dr. Matei at IU School of Medicine, Dr. Junjie Li in the Cheng lab studied the metabolic activities of cancer stem cells which remain poorly understood due to lack of sensitive single-cell analysis tools. By hyperspectral stimulated Raman scattering imaging of single living cells and mass spectrometry analysis of extracted lipids, a significantly increased level of unsaturated lipids in sorted ovarian cancer stem cells (CSCs) was found as compared to non-CSCs. Furthermore, in either cell lines or primary cells isolated from patient malignant ascites, a higher lipid unsaturation level was detected in CSC-enriched spheroids compared to monolayer culture. Inhibition of lipid desaturases effectively eliminated the CSCs and significantly suppressed sphere formation. Pretreatment of cancer cells with lipid desaturase inhibitors significantly retarded tumor formation in vivo. These findings collectively demonstrate increased lipid unsaturation as a metabolic marker of ovarian CSCs and as a target for CSC-specific therapy