Liquid chromatography coupled with mass spectroscopy (LC/MS) is rapidly evolving as a method of choice for chemical phenotyping of biological systems. Targeted, non-targeted and hybrid methods provide effective means to detect and quantify a broad range of small molecules, including amino acids, lipids, sugars, drugs and environmental chemicals, in cells, tissues, or biofluids. Applications include metabolite profiling of tumor samples, identifying disease biomarkers, and studying complex biological networks.
Our group has developed high-resolution metabolomics platforms that can comprehensively evaluate over 10,000 chemicals, including biological metabolites, dietary intakes and environmental exposures. This approach has been applied to a large number of studies. Recent publications from the group include:
Detailed metabolomic profiles of mitochondria (Roede et al, 2012); integrated proteomics and metabolomics to study mechanisms of cadmium toxicity (Go et al, 2014); comparative metabolomics of seven mammalian species (Park et al, 2012); Parkinson’s disease progression (Roede et al, 2013); monitoring of red blood cell storage in the blood bank (Roback et al, 2014); metabolome wide association study of neovascular age-related macular degeneration (Osborn et al, 2013); metabolic consequences of marginal vitamin B-6 deficiency (Gregory et al, 2013); aging in an American Indian cohort (Zhao et al, 2014); aging in fruit fly models (Hoffman et al, 2014); metabolomic profiles associated with oxidative stress in severe asthma (Fitzpatrick et al, 2014); metabolomics of bronchoalveolar lavage samples in HIV cohorts (Cribbs et al, 2014); biomarkers for lung injury after lung transplantation (Neujahr et al, 2014); molecular mechanisms in innate immunity (Ravindran et al, 2014); and several works on method development (Soltow et al, 2013; Yu et al, 2013; Uppal et al, 2013; Li et al, 2013b).
Metabolic network associated with aging in fruit fly. The network shown here represents output from mummichog analysis (Li et al, 2013b) with color hue determined by the sign and size and color intensity determined by the magnitude of the regression coefficient in the age model (blue is negative, red is positive). The metabolites are putatively annotated based on m/z ratio. This particular module is enriched for metabolites associated with glycolysis, for metabolites that feed the glycolytic pathway, and for metabolites associated with glycophospholipid metabolism (Hoffman et al, 2014).
Metabolites detected by LC-MS metabolomics during YFV infection of dendritic cells. A) A subnetwork of metabolic changes after YFV infection. Warm colors indicate increased concentration, cold colors decreased concentration from cell extracts (Li et al, 2013b). B) The metabolic reaction of arginine converted to citrulline during YFV infection, from 30 minutes to 6 hours (Ravindran et al, 2014).