Mass Spectrometry Laboratory at National Jewish Health

Mass Spectrometry Laboratory (MSL) at NJH represents a rare research facility mostly dedicated to a focused quantitative analysis of lipid signaling molecules and other small molecules by the LC-MS/MS with a special emphasis given to the detection of a low level bioactive analytes. MSL provides analytical expertise as well as mentoring in the area of lipid analyses. Access to MSL is opened to NJH employers and to outside academic institutions. Interaction with for-profit organization can be arranged on a contractual basis.MSL is built on the unique expertise established throughout the years in the area of targeted quantitative analysis of sphingolipid an lysophospholipid signaling molecules. The success of employed methodologies is proved by support given to several successful NIH-funded R01 and Program Project grant applications.

MSL is currently equipped with Sciex 6500 QTRAP low resolution hybrid triple quadrupole ion trap mass spectrometer interfaced with Schimadzu Nexera X2 UHPLC system. This instrument is ideal for targeted (quantitative) analyses and structure elucidation studies but can perform partial non-targeted profiling experiments. We are looking at a possibility to expand our instrument park into a high resolution Sciex 6600 TripleTOF mass spectrometer with Selexion ion mobility front end separation capabilities to allow full metabolomic/lipidomic studies.

Our current analytical activities are focused at, but not limited to, sphingolipid signaling molecules, endocannabinoids, and bioactive lysophospholipids. Sphingolipids fulfill a critical role in regulating a pleufora of signaling pathways controlling, within others, cell proliferation, survival, and death. Sphingosine-1-phosphate, ceramides, and sphingosine are the most prominent sphingolipid bioactive molecules involved in regulation of critical cellular functions. Intertwined metabolic pathways put all sphingolipids into a web of metabolic transformations ultimately controlling the fate of biological system. Maintaining proper homeostasis between different sphingolipid signaling molecules is paramount, and its shift in different pathological conditions is a focus for potential therapeutic interventions. This interconnection emphasizes the need for a proper quantitation of all related metabolites often fulfilling an opposite signaling function in cells. Endocannabinoids anandamide and 2- arachidonoylglycerol (2-AG), together with cannabinoid CB1 and CB2 receptors, are part of the endocannabinoid signaling system which regulates neurotransmission, inflammation, and fibrogenesis. We have developed unique protocol allowing precise quantitation of anandamide along with multiple other fatty acid ethanolamides and 2-AG. Recent focus at skin lipids drives our methodological development towards proper identification and measurement of the unusual skin sphingolipids as well as other polar and non-polar metabolites. The workflow developed by us allows the analyses of lipid and polar analytes in just one skin tape strip thus ensuring our capabilities to perform skin stratification studies. As a goal, we are working at the extension of the spectrum of quantified biologically active lipids and at the expansion towards classical metabolomics/lipidomics to be able to provide comprehensive overview of lipidome and metabolome along with focused quantitative view at selected signaling metabolites..