| Lipid Signaling | Chemical Probes | Metabolomics |
In
humans, pathological alterations in lipid metabolism and signaling can lead to
inflammatory and metabolic disorders, and drugs that target
these biochemical pathways serve as effective therapies for inflammation/pain
(NSAIDs), cardiovascular disorders (Lipitor®), obesity (Alli®),
asthma (Singulair®), and multiple sclerosis (Gilenya®).
The large number of orphan proteins encoded within the human genome argues for
the existence of additional undiscovered lipid metabolic/signaling pathways
important for human disease. In support of this hypothesis, our own studies of
lipid signaling pathways have led to the discovery of a previously
unappreciated DAGLβ-regulated
pathway in macrophages. We are interested in utilizing mass spectrometry-based metabolomics to achieve a deeper understanding of metabolic regulation in immune cell function and fate. Future studies will focus on advancing MS-based metabolomic methods to expand the diversity of lipid species measured to facilitate the assignment of physiological substrates and products regulated by metabolic enzymes of interest.
Representative publications
1. K.L. Hsu et al., DAGLbeta inhibition perturbs a lipid network involved in macrophage inflammatory responses. Nat Chem Biol 8, 999 (2012).
2. T.W. Grim et al., Combined inhibition of FAAH and COX produces enhanced anti-allodynic effects in murine neuropathic and inflammatory pain models. Pharmacol Biochem Behav 124, 405 (2014).
1. K.L. Hsu et al., DAGLbeta inhibition perturbs a lipid network involved in macrophage inflammatory responses. Nat Chem Biol 8, 999 (2012).
2. T.W. Grim et al., Combined inhibition of FAAH and COX produces enhanced anti-allodynic effects in murine neuropathic and inflammatory pain models. Pharmacol Biochem Behav 124, 405 (2014).