Oxidative stress, carcinogenesis, cardiovascular disease, and neurodegenerative disease
Oxidative stress results in damage to lipids through the formation of lipid hydroperoxides. Our laboratory is involved in determining the factors that control lipid hydroperoxide-mediated damage to DNA, and proteins. We are also characterizing the lesions in these macromolecules using novel mass spectrometry methodology, determining how the lesions affect proliferation and apoptosis using model in vitro systems, and assessing how such processes can be prevented using novel pharmacological agents. We also have a program in biomarker discovery and analysis, which is focused on metabolomic and proteomic biomarkers of smoking, pancreatic cancer, breast cancer, and neurodegenerative diseases. This involves the use of quantitative stable isotope dilution liquid chromatography-mass spectrometry methodology. We recently implement the use of stable isotope dilution by essential nutrients in cell culture (SILEC) as a method for analyzing important Krebs cycle coenzyme A-thioesters. This has made it possible to examine the effects of chemicals and disease on mitochondrial dysfunction.
Selected Publications
Tamae D, Byrns M, Marck B, Mostaghel EA, Nelson PS, Lange P, Lin D, Taplin ME, Balk S, Ellis W, True L, Vessella R, Montgomery B, Blair IA, Penning TM. : Development, validation and application of a stable isotope dilution liquid chromatography electrospray ionization/selected reaction monitoring/mass spectrometry (SID-LC/ESI/SRM/MS) method for quantification of keto-androgens in human serum. J Steroid Biochem Mol Biol. 138C: 281-289, July 2013.
Lee I, Dodia C, Chatterjee S, Zagorski J, Mesaros C, Blair IA, Feinstein SI, Jain M, Fisher AB.: A novel non-toxic inhibitor of the activation of NADPH oxidase (NOX2) reduces reactive oxygen species production in mouse lung. J Pharmacol Exp Ther. 345(2): 284-96, 2013.
Strasser AA, Ashare RL, Kaufman M, Tang KZ, Mesaros C, Blair IA: The effect of menthol on cigarette smoking behaviors, biomarkers and subjective responses. Cancer Epidemiol Biomarkers Prev. 22(3): 382-389, 2013.
Snyder N, Khezam M, Mesaros AC, Worth A, and Blair IA. : Untargeted Metabolomics from Biological Sources Using Ultraperformance Liquid Chromatography- High Resolution Mass Spectrometry (UPLC-HRMS). J Vis Exp.(75), 2013 Notes: doi: 10.3791/50433.
Huang M, Blair IA, Penning TM. : Identification of stable benzo[a]pyrene-7,8-dione-DNA adducts in human lung cells. Chem Res Toxicol 26(5): 685-692, 2013.
Hammons AL, Summers CM, Jochems J, Arora JS, Zhang S, Blair IA, Whitehead AS. : Pemetrexed alters folate phenotype and inflammatory profile in EA.hy 926 cells grown under low-folate conditions. Eur J Pharmacol 696(1-3): 12-17, Dec 2012.
Hood ED, Greineder CF, Dodia C, Han J, Mesaros C, Shuvaev VV, Blair IA, Fisher AB, Muzykantov VR: Antioxidant protection by PECAM-targeted delivery of a novel NADPH-oxidase inhibitor to the endothelium in vitro and in vivo. J Control Release 163(2): 161-169, Oct 2012.
MacDonald ML, Ciccimaro E, Prakash A, Banerjee A, Seeholzer SH, Blair IA, Hahn CG: Biochemical Fractionation and Stable Isotope Dilution Liquid Chromatography-Mass Spectrometry for Targeted and Microdomain-Specific Protein Quantification in Human Postmortem Brain Tissue. Mol Cell Proteomics 11(12): 1670-1681, Aug 2012.
Zhang L, Huang M, Blair IA, Penning TM: Detoxication of Benzo[a]pyrene-7,8-dione by Sulfotransferases (SULT) in Human Lung Cells. J. Biol. Chem 287(35): 29909-20, Jul 2012.
Ashare RL, Tang KZ, Mesaros AC, Blair IA, Leone FT, Strasser AA. (2012) : Effects of 21 days of varenicline versus placebo on smoking behaviors and urges among non-treatment seeking smokers. J Psychopharmacol 10: 1383-90, June 2012.
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Last updated: 08/01/2013
The Trustees of the University of Pennsylvania