Department of Pharmacology & Chemical Biology at the University of Pittsburgh
Marco Fazzari, PhD
Research Assistant Professor
200 Lothrop Street E1340 Thomas E. Starzl Biomedical Science Tower
Pittsburgh, PA 15261

Email:
maf167@pitt.edu
Phone: 412-626-2924

Fax: 412-648-2229


Education

M.Sc. (Pharmaceutical Chemistry and Technology Sciences), University of Palermo, Italy, 2003
Ph.D. (Mediterranean fruit culture), University of Palermo, Italy, 2008



Research Areas
Drug Discovery
Redox Pharmacology
Pharmacology of Cell and Organ Systems
Photo of Marco Fazzari, PhD

Electrophilic fatty acid nitroalkenes (NO2-FA) are products of nitric oxide and nitrite-mediated unsaturated fatty acid nitration, which mediate pleiotropic signaling actions modulating metabolic and inflammatory responses in cell and animal models. The generation of NO2-FA is promoted by inflammatory responses in cells, such as ischemia-reperfusion injury, and in the gastrointestinal tract, where acidic conditions favor the nitration of unsaturated fatty acids. So far, fatty acid nitration has been predominantly studied using free unsaturated fatty acids because of challenges in the direct mass spectrometric analysis of complex lipids and nitroalkene instability during de-esterification reactions. This is a limitation, as dietary and endogenous free fatty acid levels are proportionately very low when compared to the levels of esterified fatty acids in tissue compartments and foods.

 

My research projects are all directed towards developing a basic understanding of the biological generation and metabolism of electrophilic lipid signaling mediators, which have only been partially studied and still remains a large gap in knowledge regarding the detection, characterization and physiologic actions of NO2-FA-containing complex lipids. Recently I have shown that sources of unsaturated fatty acid-containing triacylglycerides in the diet (e.g. plant or animal lipids) support the formation of NO2-FA upon digestion.

 

 

Furthermore, the direct nitration of complex lipids or the incorporation of free NO2-FA into triglycerides in adipocytes form a reservoir of electrophilic lipids that can react directly with nucleophilic targets or mediate signaling actions upon hydrolysis to free NO2-FA by cellular lipases.

 

 

Finally, I have focused my research interests on the acidic gastric nitration of conjugated linoleic acid (CLA)-containing lipids which generates of unstable nitro-nitrate intermediates. Decomposition of these species, which are spontaneous at physiological pH for free CLA-derived products and catalyzed by lipase-mediated hydrolysis for nitro-nitrate triglycerides, yield nitro-conjugated linoleic acid (NO2-CLA), active nitrogen oxide and nitrosating species with potential beneficial effects.





Important Publications
M Fazzari, N Khoo, SR Woodcock, DK Jorkasky, L Li, FJ Schopfer and BA Freeman. Nitro-fatty acid pharmacokinetics in the adipose tissue compartment. Journal of Lipid Research 58:375-385, 2017. 
SR Salvatore, DA Vitturi, M Fazzari, DK Jorkasky and FJ Schopfer. Evaluation of 10-nitro oleic acid bio-elimination in rats and humans. Scientific Reports 7: 39900, 2017.
M Fazzari, N Khoo, SR Woodcock, L Li, BA Freeman and FJ Schopfer. Generation and esterification of electrophilic fatty acid nitroalkenes in triacylglycerides. Free Radical Biology & Medicine 87:113-124, 2015. 
DA Vitturi, L Minarrieta, SR Salvatore, EM Postlethwait, M Fazzari, G Ferrer-Sueta, JR Lancaster, BA Freeman and FJ Schopfer. Convergence of biological nitration and nitrosation reactions via symmetrical nitrous anhydride. Nature Chemical Biology 11:504-510, 2015.
M Fazzari, A Trostchansky, F.J Schopfer, SR Salvatore, B Sanchez-Calvo, D Vitturi, R Valderrama, JB Barroso, R Radi, BA Freeman and H Rubbo. Olives and olive oil are sources of electrophilic Fatty Acid nitroalkenes. PLoS One 9:e84884, 2014.




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