The mission of Core A: Mass Spectrometry Core is to provide access to advanced mass spectrometry equipment for Pharmacology Center investigators and to provide assistance to investigators for development of novel analytical methods.
The specific aims of this core are:
Specific Aim 1 ? Develop ultra-high sensitivity LC-MS/MS protocols for characterization and quantitation of complex lipid and drug metabolite samples using nanoflow UPLC techniques and the proposed high sensitivity Quantum Vantage mass spectrometer.
Specific Aim 2 - Develop sophisticated data-dependent scanning protocols for characterization of complex lipid and drug metabolite profiles for structural determination, similar to techniques employed by proteomics laboratories, using nanoflow LC and high resolution MS.
Specific Aim 3 - Develop derivatization strategies to improve sensitivity for analysis of molecules with poor intrinsic ionization properties. These services will employ primarily liquid chromatography-tandem mass spectrometry (LC-MS/MS) for quantitation of biomolecules in tissues and fluids, identification of novel reactive oxidation products of lipids, and identification of protein adducts of reactive species. The core will use the MS equipment provided by the Vanderbilt University Mass Spectrometry Research Center, which includes a comprehensive small molecule mass spectrometry core (MS Core) and a state-of-the-art proteomics core. The instrumentation available to investigators includes a variety of low resolution (four triple quadrupole, two LTQ ion trap) and two high resolution (an Orbitrap FT-MS and a Q-TOF) LC-MS/MS instruments, many of which are equipped with ultra-high pressure liquid chromatographs for high efficiency separation of complex mixtures. In addition, we propose to purchase a new high sensitivity triple quadrupole MS equipped with a nanospray ion source and a nanoflow UPLC system. The combination of nanoflow LC with a state-of-the-art triple quadrupole MS will achieve about 100-fold greater sensitivity than currently possible with existing equipment. This increased performance will specifically benefit Project 1 (PI LJ Roberts), Project 2 (PI: JA Oates) and Project 5 (PI: AR Brash).

Public Health Relevance

The role of the Mass Spectrometry Core is to provide assistance to the project leaders for the analysis of complex mixtures of oxidized lipids and drug metabolites resulting from damage to tissues. Mass spectrometry will be used to determine the amount of the oxidized lipids present and also to determine the chemical identity of the oxidized lipid and other drug metabolites. In order to perform these duties, the MS Core will require a new high sensitivity mass spectrometer.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM015431-46
Application #
8489130
Study Section
Special Emphasis Panel (ZGM1-PPBC-6)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
46
Fiscal Year
2013
Total Cost
$65,151
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Teder, Tarvi; Boeglin, William E; Brash, Alan R (2017) Oxidation of C18 Hydroxy-Polyunsaturated Fatty Acids to Epoxide or Ketone by Catalase-Related Hemoproteins Activated with Iodosylbenzene. Lipids 52:587-597
Teder, Tarvi; Boeglin, William E; Schneider, Claus et al. (2017) A fungal catalase reacts selectively with the 13S fatty acid hydroperoxide products of the adjacent lipoxygenase gene and exhibits 13S-hydroperoxide-dependent peroxidase activity. Biochim Biophys Acta 1862:706-715
Plewes, Katherine; Kingston, Hugh W F; Ghose, Aniruddha et al. (2017) Cell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria: an observational study. BMC Infect Dis 17:313
Kong, Deping; Li, Juanjuan; Shen, Yujun et al. (2017) Niacin Promotes Cardiac Healing after Myocardial Infarction through Activation of the Myeloid Prostaglandin D2 Receptor Subtype 1. J Pharmacol Exp Ther 360:435-444
Gamble-George, Joyonna Carrie; Baldi, Rita; Halladay, Lindsay et al. (2016) Cyclooxygenase-2 inhibition reduces stress-induced affective pathology. Elife 5:
Adeniji, Adegoke; Uddin, Md Jashim; Zang, Tianzhu et al. (2016) Discovery of (R)-2-(6-Methoxynaphthalen-2-yl)butanoic Acid as a Potent and Selective Aldo-keto Reductase 1C3 Inhibitor. J Med Chem 59:7431-44
Kudalkar, Shalley N; Kingsley, Philip J; Marnett, Lawrence J (2016) Assay of Endocannabinoid Oxidation by Cyclooxygenase-2. Methods Mol Biol 1412:205-15
Wu, Jing; Montaniel, Kim Ramil C; Saleh, Mohamed A et al. (2016) Origin of Matrix-Producing Cells That Contribute to Aortic Fibrosis in Hypertension. Hypertension 67:461-8
Harrison, D G; Guzik, Tomasz J (2016) Macrophages come to mind as keys to cognitive decline. J Clin Invest 126:4393-4395
Montaniel, Kim Ramil C; Harrison, David G (2016) Is Hypertension a Bone Marrow Disease? Circulation 134:1369-1372

Showing the most recent 10 out of 149 publications