Metabolomics Research

Mass spectrometry-based metabolomics is the primary high-throughput technique used in the Lyssiotis lab. We have optimized targeted metabolomics analysis pipelines (named Snapshot Metabolomics; Figure 1) for quantification of ~250 metabolites using Agilent triple-quadrupole (QqQ) mass spectrometry systems. Our platform utilizes two chromatographic methods, reversed-phase and hydrophilic interaction liquid chromatography (RPLC and HILIC), to maximize the coverage of metabolites. We have applied this Snapshot Metabolomics for detection of differentially altered metabolites in cell lysates, media supernatant, human and animal samples, and can tailor it to several specific metabolites of interest. Besides Snapshot Metabolomics, our lab has expertise in stable isotope tracing of labelled metabolites, e.g. 13C-glucose, 13C-glutamine, or 13C-serine. With isotope tracing, we delineate the intracellular fate of metabolites, thus gain unprecedented insights into a cellular distribution of metabolism in a normal or perturbed state (e.g. following genetic manipulation or drug treatment).

We have successfully applied both Snapshot Metabolomics and isotope tracing in several projects (e.g. Sousa et al., Nature 2016; Halbrook et al. Cell Metabolism 2019), and are constantly open to collaborating on new project ideas that push the boundaries of our methods. Moreover, we have recently carried out meta-analysis of a large-scale compendium of heterogeneous targeted metabolomics data generated from our platform in a bid to establish high-confidence metabolites and gain insights into metabolite dynamics across a wide range of different biological conditions (Lee et al. Metabolomics 2019).

Selected Publications

Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion.
Sousa CM, Biancur DE, Wang X, Halbrook CJ, Sherman MH, Zhang L, Kremer DK, Hwang RF, Witkiewicz AK, Ying H, Evans RM, Cantley LC, Lyssiotis CA, Kimmelman AC. Nature (2016) 236 (7617) 479-83
Abstract | PDF

Macrophage Released Pyrimidines Inhibit Gemcitabine Therapy in Pancreatic Cancer.
Halbrook CJ, Pontious C, Kovalenko I, Lapienyte L, Dreyer S, Lee H-J, Thurston G, Zhang Y, Lazarus J, Sajjakulnukit P, Hong HS, Kremer DM, Nelson BS, Kemp S, Zhang L, Chang D, Biankin A, Shi J, Frankel TL, Crawford HC, Morton JP, Pasca di Magliano M, Lyssiotis CACell Metabolism (2019) 29 (6) 1390-1399
Abstract | PDF 

A large-scale analysis of targeted metabolomics data from heterogenous biological samples provides insights into metabolite dynamics
Lee H-J, Kremer DM, Sajjakulnukit P, Zhang L,
Lyssiotis CA. Metabolomics (2019) 15 (7) 103
Abstract | PDF