Stable Isotope & Metabolomics Core

Leadership

Director: Irwin Kurland, MD 

Seahorse Technician: Xue-Liang Du, PhD 

Bioinformatic specialist: Li Liu 

Location:  Price 368

Seahorse Location: Forchheimer 529

Request Services

• For Seahorse: xueliang.du@einsteinmed.org 
• For Mass Spectrometric assays : irwin.kurland@einsteinmed.org and Yunping.qiu@einsteinmed.org 
• For Bioinformatics : Li.Liu@einstein.yu.edu 

Mission

To accomplish these goals in one facility, the SIMC has updated its technology infrastructure to include the latest Seahorse XFe24 and XFe96 Seahorse Flux Analyzers for assessment of glycolytic and mitochondrial energetics, as well as the latest Sciex 6500+ QTRAP with Selexion ion mobility for targeted LC/MS metabolite and lipidomic analyses, and the latest Shimadzu LC-9030 quadrupole Time of Flight with Nexera UPLC for untargeted metabolomic and lipidomic analyses. 

Objectives

1. To determine metabolomic/lipidomic profiles for the diagnosis/characterization of physiological and pathophysiological states in cells, tissues and biofluids (plasma, urine, stool, etc.).
2. To perform in vivo stable isotope substrate assays to determine rates of protein synthesis, lipogenesis, peripheral glucose disposal, hepatic glucose recycling, glucose-glycerol cycling and Cori cycling, high energy phosphate (ATP, creatine phosphate) turnover, and in vitro stable isotope flux dissections of metabolic pathways.
3. To perform assessments of glycolysis (extracellular acidification rates, glycolytic ATP production rates) and mitochondrial oxygen consumption (mitochondrial respiration and mitochondrial ATP production rates) in tissue explants, primary isolated and tissue culture cells using Seahorse Biosciences Flux Analyzers.
4. To advise and instruct ES-DRC investigators and their students, fellows and technical staff in the design and interpretation of fluxomics, metabolomics/lipidomics and computational analyses with the aim of elucidating the molecular basis underlying glucose and lipid homeostasis in humans and animal models.

New Developments

1. A Shimadzu-Einstein Mass Spectrometry Innovation Center has been established, starting with the development of applications and protocols for the new Shimadzu LC-9030 quadrupole Time of Flight.
2. Widely targeted Lipidomic Profiling (WTLP) using the Sciex 6500+ QTRAP: Our newly developed widely targeted lipidomic profiling (WTLP) method employs a MRM based fragmentation method for the Sciex 6500+, combined with Avanti SPLASH© and Lipidyzer© standards, to design a WTLP method for detection and quantitation of ~1300 lipid species in 26 lipid classes, including Ceramides (CER), Cholesterol (CHOL), Cholesterol ester (CE), diacylglycerol (DAG), Triacylglycerol (TAG), dihydroceramides (DCER), free fatty acids (FFA), hexosylceramides (HCER), lactosylceramide (LCER), phosphatidylcholine (PC), phosphatidylethanolamine (PE), lyso-PC (LPC), lyso-PE (LPE), sphingomyelin (SM), phosphatidic acid (PA), phosphatidylinositol (PI), phosphatidylglycerol (PG) and phosphatidylserine (PS). In human plasma, 600-700 lipid species have a coefficient of variation (CV) <30%.
3. Widely targeted small polar metabolite panel (WTSM) using the Sciex 6500+ QTRAP: The Sciex 6500+ QTRAP, with ~550+ annotated metabolites when only the C18 column is used, covers a substantial portion of key metabolite pathways, such as amino acids, amines, acyl carnitines, organic acids (TCA metabolites, glycolytic metabolites including lactate/pyruvate), bile acids and fatty acids. Including HILIC chromatography for tissue samples, raises the detection ability to ~650+. In human plasma, ~200 metabolites are found with a coefficient of variation (CV) <30% and for urine ~300 metabolites are found with CVs <30% for the C18 column method alone.
4. SIMC is now offering a new Computational Chemistry and Molecular Modeling Service that includes the following:
• a. structural modeling
• b. protein-protein & protein-small molecule interactions
• c. cheminformatics, quantitative structure–activity relationship (QSAR) and virtual high throughput screening (vHTS)
• d. assistance available for the inclusion of computational chemistry and molecular modeling in grant applications and manuscript preparation