Quantitative Mass Spectrometry incorporates collaborative projects in which the Mass Spectrometry Group provides quantitative information about, typically, small molecules by GCMS, LCMS and LCMSMS or a combination. An example of the types of projects this includes is the isoprostane analyses undertaken as part of the NIEHS led study of biomarkers of oxidative stress. We currently have several major collaborations underway. 1) with the Zeldin Lab quantitating arachidonic acid metabolites that are relevant to inflammatory, vasodilatory, endothelial protective and post-ischemic cardioprotective effects. We ahve also provided quantiative information relevant to research identifying the role of epoxyeicosatrienoic acids in the control of angiogenesis-dependent regeneration, cancer, and metastasis. 2) a collaboration with James Mohler/Mark Titus on a Program Project (UNC/Roswell Cancer Institute) on Interference with the Androgen Receptor and its Ligands in Recurrent Prostate Cancer. As part of this study, we have: a) successfully developed an LC/MS/MS protocol for the analysis of T, DHT, dihydroepiandrosterone, androsterone, 5-androstenediol, and androstenedione at the low femtomolar level (0.15 to 9 fM except for the saturated diol) based on the use of atmospheric pressure photoionization (APPI). Enhanced sensitivity for non-conjugated ketosteroids, such as DHT, was achieved via the monitoring of an (M+14)+ ion arising from alkylation of the analyte by the methanolic solvent used in APPI. (Patent application pending;b)applied our APPI assay to the quantitation of these analytes in diverse CaP cell lines. In these experiments, either T in combination with inhibitor or 3-androstandediol, was added to the cell lines and DHT levels were measured after 48 hrs incubation. 3) Investigating the relationship between levels of EETs and DHETs and blood pressure, and levels of prostaglandin E2 and pulmonary fibrosis 4) Quantitate Bisphenol A exposure from rodent bedding and diet to help assess the importance given to the estrogenic content of the animal's diet, bedding, caging, and water bottles when evaluating the estrogenic activity of bisphenol A.

Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2011
Total Cost
$321,703
Indirect Cost
City
State
Country
Zip Code
Winuthayanon, Wipawee; Bernhardt, Miranda L; Padilla-Banks, Elizabeth et al. (2015) Oviductal estrogen receptor ? signaling prevents protease-mediated embryo death. Elife 4:e10453
Sayers, Brian C; Taylor, Alexia J; Glista-Baker, Ellen E et al. (2013) Role of cyclooxygenase-2 in exacerbation of allergen-induced airway remodeling by multiwalled carbon nanotubes. Am J Respir Cell Mol Biol 49:525-35
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Graves, Joan P; Edin, Matthew L; Bradbury, J Alyce et al. (2013) Characterization of four new mouse cytochrome P450 enzymes of the CYP2J subfamily. Drug Metab Dispos 41:763-73
Pattabiraman, Padmanabhan P; Lih, Fred B; Tomer, Kenneth B et al. (2012) The role of calcium-independent phospholipase A2? in modulation of aqueous humor drainage and Ca2+ sensitization of trabecular meshwork contraction. Am J Physiol Cell Physiol 302:C979-91
Theken, Katherine N; Schuck, Robert N; Edin, Matthew L et al. (2012) Evaluation of cytochrome P450-derived eicosanoids in humans with stable atherosclerotic cardiovascular disease. Atherosclerosis 222:530-6
Panigrahy, Dipak; Edin, Matthew L; Lee, Craig R et al. (2012) Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice. J Clin Invest 122:178-91

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